Pub Date : 2024-12-01Epub Date: 2023-12-27DOI: 10.1080/16078454.2023.2293513
Lin Liu, Jinghan Wang, Huan Xu, Shuqi Zhao, Lu Wang, Jiansong Huang, Huanping Wang, Hongyan Tong, Jie Jin
Objectives: In patients with acute promyelocytic leukemia (APL), additional chromosomal abnormalities (ACAs) are prognostic indicators. However, the clinical features of ACAs were not systematically reported in Chinese patients. Therefore, we enrolled a large cohort of APLs to demonstrate the clinical characteristics and prognostic value of ACAs.
Methods: 268 patients with newly diagnosed APL with t(15;17)(q24;q21) were retrospectively enrolled, and their clinical characteristics and the predictive value of ACAs were assessed between patients with the presence and absence of ACAs.
Results: APL patients with and without ACAs did not differ significantly in their clinical features or treatment response and clinical outcomes like overall survival (OS) and disease-free survival (DFS). It appeared to be substantially associated with worse OS in APL patients with trisomy 8, which was the most common ACA, although DFS was unaffected. Interestingly, the presence of ACAs or trisomy 8 affected OS and DFS in the subgroup of patients aged ≥60 years; by contrast, ACAs had no effect on OS or DFS in any treatment subgroup (ATRA + ATO/RIF or ATRA + ATO/RIF + CH or ATRA + CH), except for the ATRA + ATO/RIF + CH treatment subgroup, where their impact on DFS was less favorable.
Conclusions: Our results suggested that OS and DFS were unaffected by ACAs. Nonetheless, in the subgroup of patients older than 60, the existence of ACAs or trisomy 8 appeared to impact OS and DFS negatively. Individuals with t(15;17) alone had a higher DFS and were more susceptible to ATRA + ATO/RIF + CH than individuals with t(15;17) ACAs.
{"title":"Prognosis influence of additional chromosome abnormalities in newly diagnosed acute promyelocytic leukemia with t(15;17)(q24;q21).","authors":"Lin Liu, Jinghan Wang, Huan Xu, Shuqi Zhao, Lu Wang, Jiansong Huang, Huanping Wang, Hongyan Tong, Jie Jin","doi":"10.1080/16078454.2023.2293513","DOIUrl":"10.1080/16078454.2023.2293513","url":null,"abstract":"<p><strong>Objectives: </strong>In patients with acute promyelocytic leukemia (APL), additional chromosomal abnormalities (ACAs) are prognostic indicators. However, the clinical features of ACAs were not systematically reported in Chinese patients. Therefore, we enrolled a large cohort of APLs to demonstrate the clinical characteristics and prognostic value of ACAs.</p><p><strong>Methods: </strong>268 patients with newly diagnosed APL with t(15;17)(q24;q21) were retrospectively enrolled, and their clinical characteristics and the predictive value of ACAs were assessed between patients with the presence and absence of ACAs.</p><p><strong>Results: </strong>APL patients with and without ACAs did not differ significantly in their clinical features or treatment response and clinical outcomes like overall survival (OS) and disease-free survival (DFS). It appeared to be substantially associated with worse OS in APL patients with trisomy 8, which was the most common ACA, although DFS was unaffected. Interestingly, the presence of ACAs or trisomy 8 affected OS and DFS in the subgroup of patients aged ≥60 years; by contrast, ACAs had no effect on OS or DFS in any treatment subgroup (ATRA + ATO/RIF or ATRA + ATO/RIF + CH or ATRA + CH), except for the ATRA + ATO/RIF + CH treatment subgroup, where their impact on DFS was less favorable.</p><p><strong>Conclusions: </strong>Our results suggested that OS and DFS were unaffected by ACAs. Nonetheless, in the subgroup of patients older than 60, the existence of ACAs or trisomy 8 appeared to impact OS and DFS negatively. Individuals with t(15;17) alone had a higher DFS and were more susceptible to ATRA + ATO/RIF + CH than individuals with t(15;17) ACAs.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2293513"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-03-21DOI: 10.1080/16078454.2024.2331389
Hongyu An, Shiming Chen, Xin Zhang, Shandong Ke, Jinyong Ke, Yalan Lu
Objective: Plant homeodomain finger protein 19 (PHF19) regulates hematopoietic stem cell differentiation and promotes multiple myeloma (MM) progression. This study intended to explore the potency of PHF19 at baseline and post induction treatment in estimating treatment response to protease inhibitors and survival in MM patients.
Methods: This retrospective study screened 69 MM patients who received protease inhibitors with bone marrow (BM) samples available at both baseline and post induction treatment. Twenty healthy BM donors were included as healthy controls (HCs). PHF19 in plasma cells from BM was quantified by reverse transcription-quantitative polymerase chain reaction.
Results: PHF19 at baseline and post induction treatment in MM patients were increased than in HCs. In MM patients, PHF19 was declined post induction treatment. Elevated PHF19 at baseline and post induction treatment were correlated with renal impairment, beta-2-microglobulin ≥5.5 mg/L, t (4; 14), higher international staging system (ISS) stage, and higher revised ISS (R-ISS) stage. Concerning treatment response, PHF19 at baseline and post induction treatment were negatively associated with complete response and overall response rate. Notably, abnormal PHF19 (above 95% quantile value of PHF19 in HCs) at baseline and post induction treatment were linked with shortened event-free survival (EFS) and overall survival (OS). After adjustment, abnormal PHF19 post induction treatment was independently related to shortened EFS (hazard ratio = 2.474) and OS (hazard ratio = 3.124).
Conclusion: PHF19 is aberrantly high and declines post induction therapy, which simultaneously reflects unfavorable treatment response to protease inhibitors as well as shorter EFS and OS in MM patients.
{"title":"PHF19 before and post induction treatment possess favorable potency of reflecting treatment response to protease inhibitors, event-free survival, and overall survival in multiple myeloma patients.","authors":"Hongyu An, Shiming Chen, Xin Zhang, Shandong Ke, Jinyong Ke, Yalan Lu","doi":"10.1080/16078454.2024.2331389","DOIUrl":"10.1080/16078454.2024.2331389","url":null,"abstract":"<p><strong>Objective: </strong>Plant homeodomain finger protein 19 (PHF19) regulates hematopoietic stem cell differentiation and promotes multiple myeloma (MM) progression. This study intended to explore the potency of PHF19 at baseline and post induction treatment in estimating treatment response to protease inhibitors and survival in MM patients.</p><p><strong>Methods: </strong>This retrospective study screened 69 MM patients who received protease inhibitors with bone marrow (BM) samples available at both baseline and post induction treatment. Twenty healthy BM donors were included as healthy controls (HCs). PHF19 in plasma cells from BM was quantified by reverse transcription-quantitative polymerase chain reaction.</p><p><strong>Results: </strong>PHF19 at baseline and post induction treatment in MM patients were increased than in HCs. In MM patients, PHF19 was declined post induction treatment. Elevated PHF19 at baseline and post induction treatment were correlated with renal impairment, beta-2-microglobulin ≥5.5 mg/L, <i>t</i> (4; 14), higher international staging system (ISS) stage, and higher revised ISS (R-ISS) stage. Concerning treatment response, PHF19 at baseline and post induction treatment were negatively associated with complete response and overall response rate. Notably, abnormal PHF19 (above 95% quantile value of PHF19 in HCs) at baseline and post induction treatment were linked with shortened event-free survival (EFS) and overall survival (OS). After adjustment, abnormal PHF19 post induction treatment was independently related to shortened EFS (hazard ratio = 2.474) and OS (hazard ratio = 3.124).</p><p><strong>Conclusion: </strong>PHF19 is aberrantly high and declines post induction therapy, which simultaneously reflects unfavorable treatment response to protease inhibitors as well as shorter EFS and OS in MM patients.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2331389"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: Accurate epidemiological data are crucial for effective disease prevention and treatment. We conducted a large-scale survey to explore the thalassaemia prevalence and spectrum among the two major ethnic groups in Hainan Province.
Methods: A total of 399,053 childbearing-age individuals of Li (n = 77,563) and Han(n = 321,490) ethnic groups were recruited from 18 cities and counties in Hainan, and their thalassemia genotypes were systematically screened and statistically analysed.
Results: This study revealed a significantly higher thalassaemia carrier rate in the Li (55.39%) than that in the Han (13.13%). Specifically, the carrier rate of α-thalassaemia was 46.39% in the Li and 10.02% in the Han. The predominant α-thalassaemia mutations were - α3.7 and - α42. in Li, whereas the main mutation were - SEA and - α4.2 in Han. For β-thalassaemia, the carrier rates were 1.68% in Li and 2.38% in Han, with CD41-42(-CTTT) the most prevalent mutation in both groups. The carrier rates of β-/α-compound thalassaemia were 7.32% in Li and 0.73% in Han. Additionally, there were regional differences in the distribution of thalassemia among the Li and Han within Hainan Province.
Conclusion: Epidemiological characteristics and molecular spectrum of thalassaemia among the Li and Han ethnic groups in Hainan were revealed in this study. These findings can provide a scientific basis to develop and implement prevention strategies for thalassaemia in Hainan.
{"title":"Prevalence of thalassaemia among childbearing-age Li and Han populations in Hainan Province.","authors":"Fangchao Tao, Yanquan Lai, Jiaqi Chen, Shijie Wei, Yu Zou, Yunli Lai, Qiongzhen Qin, Yufeng Wang, Wanjun Zhou","doi":"10.1080/16078454.2024.2417524","DOIUrl":"10.1080/16078454.2024.2417524","url":null,"abstract":"<p><strong>Objectives: </strong>Accurate epidemiological data are crucial for effective disease prevention and treatment. We conducted a large-scale survey to explore the thalassaemia prevalence and spectrum among the two major ethnic groups in Hainan Province.</p><p><strong>Methods: </strong>A total of 399,053 childbearing-age individuals of Li (<i>n </i>= 77,563) and Han(<i>n </i>= 321,490) ethnic groups were recruited from 18 cities and counties in Hainan, and their thalassemia genotypes were systematically screened and statistically analysed.</p><p><strong>Results: </strong>This study revealed a significantly higher thalassaemia carrier rate in the Li (55.39%) than that in the Han (13.13%). Specifically, the carrier rate of α-thalassaemia was 46.39% in the Li and 10.02% in the Han. The predominant α-thalassaemia mutations were - <i>α<sup>3.7</sup></i> and - <i>α<sup>42.</sup></i> in Li, whereas the main mutation were - <i><sup>SEA</sup></i> and - <i>α<sup>4.2</sup></i> in Han. For β-thalassaemia, the carrier rates were 1.68% in Li and 2.38% in Han, with <i>CD41-42(-CTTT)</i> the most prevalent mutation in both groups. The carrier rates of β-/α-compound thalassaemia were 7.32% in Li and 0.73% in Han. Additionally, there were regional differences in the distribution of thalassemia among the Li and Han within Hainan Province.</p><p><strong>Conclusion: </strong>Epidemiological characteristics and molecular spectrum of thalassaemia among the Li and Han ethnic groups in Hainan were revealed in this study. These findings can provide a scientific basis to develop and implement prevention strategies for thalassaemia in Hainan.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2417524"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-08-14DOI: 10.1080/16078454.2024.2387878
Qiang Ma, Yan Liu, Hong Zhao, Yixian Guo, Wanling Sun, Ronghua Hu
Objectives: MDS and AML characterized by TP53 variations have a poor prognosis in general. However, specifically, differences in prognosis have also been observed in patients with different TP53 variants and VAFs.Methods: Here, we retrospectively analyzed datasets of patients with MDS, MPN, and AML who underwent targeted DNA sequencing from February 2018 to December 2023, and patients with reportable TP53 variations were screened. Demographic data and clinical data were collected, and the relationship between TP53 alterations and patient prognosis (AML/MDS) was analyzed using the cBioPortal and Kaplan-Meier Plotter databases. The relationship between the VAFs of TP53 variations and prognoses was analyzed using data from the present study.Results: Sixty-two variants of TP53 were identified in 58 patients. We mainly identified single mutations (79.31%, 46/58), followed by double (17.24%, 10/58) and triple (3.45%, 2/58) mutations. The variations were mainly enriched in exon4-exon8 of TP53. Missense (72.58%, 45/62) mutations were the main type of variations, followed by splice-site (9.68%, 6/62), nonsense (9.68%, 6/62), frameshift (6.45%, 4/62), and indel (1.61%, 1/62) mutations. In this study, p.Arg175His and p.Arg273His were high-frequency TP53 mutations, and DNMT3A and TET2 were commonly co-mutated genes in the three types of myeloid neoplasms; However, we reported some new TP53 variants in MPN that have not been found in the public database. Moreover, MDS or AML characterized by altered TP53 had a shorter OS than patients in the unaltered group (P<0.01), low TP53 mRNA levels were associated with shorter OS in patients with AML (P<0.01). Data from our center further found higher VAF (≥10%) associated with shorter OS in patients with MDS (median 2.75 vs. 24 months) (P<0.01).Conclusion:TP53 mutations are mainly enriched in exon4-exon8, are missense and single mutations in myeloid neoplasms, and are associated with poor prognosis of MDS/AML, and higher VAF (≥10%) of TP53 mutations associated with a shorter OS in patients with MDS.
{"title":"Variation characteristics and clinical significance of <i>TP53</i> in patients with myeloid neoplasms.","authors":"Qiang Ma, Yan Liu, Hong Zhao, Yixian Guo, Wanling Sun, Ronghua Hu","doi":"10.1080/16078454.2024.2387878","DOIUrl":"https://doi.org/10.1080/16078454.2024.2387878","url":null,"abstract":"<p><p><b>Objectives:</b> MDS and AML characterized by <i>TP53</i> variations have a poor prognosis in general. However, specifically, differences in prognosis have also been observed in patients with different <i>TP53</i> variants and VAFs.<b>Methods:</b> Here, we retrospectively analyzed datasets of patients with MDS, MPN, and AML who underwent targeted DNA sequencing from February 2018 to December 2023, and patients with reportable <i>TP53</i> variations were screened. Demographic data and clinical data were collected, and the relationship between <i>TP53</i> alterations and patient prognosis (AML/MDS) was analyzed using the cBioPortal and Kaplan-Meier Plotter databases. The relationship between the VAFs of <i>TP53</i> variations and prognoses was analyzed using data from the present study.<b>Results:</b> Sixty-two variants of <i>TP53</i> were identified in 58 patients. We mainly identified single mutations (79.31%, 46/58), followed by double (17.24%, 10/58) and triple (3.45%, 2/58) mutations. The variations were mainly enriched in exon4-exon8 of <i>TP53</i>. Missense (72.58%, 45/62) mutations were the main type of variations, followed by splice-site (9.68%, 6/62), nonsense (9.68%, 6/62), frameshift (6.45%, 4/62), and indel (1.61%, 1/62) mutations. In this study, p.Arg175His and p.Arg273His were high-frequency <i>TP53</i> mutations, and <i>DNMT3A</i> and <i>TET2</i> were commonly co-mutated genes in the three types of myeloid neoplasms; However, we reported some new <i>TP53</i> variants in MPN that have not been found in the public database. Moreover, MDS or AML characterized by altered <i>TP53</i> had a shorter OS than patients in the unaltered group (<i>P</i><0.01), low <i>TP53</i> mRNA levels were associated with shorter OS in patients with AML (<i>P</i><0.01). Data from our center further found higher VAF (≥10%) associated with shorter OS in patients with MDS (median 2.75 vs. 24 months) (<i>P</i><0.01).<b>Conclusion:</b> <i>TP53</i> mutations are mainly enriched in exon4-exon8, are missense and single mutations in myeloid neoplasms, and are associated with poor prognosis of MDS/AML, and higher VAF (≥10%) of <i>TP53</i> mutations associated with a shorter OS in patients with MDS.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2387878"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-02-07DOI: 10.1080/16078454.2024.2310960
Jie Ding, Yang Su, Yinglu Ruan, Nan Li, Qianchao Meng, Jiabang Yang, Li Chen, Chi Liu
Objective: To investigate efficacy and prognostic factors in the treatment of adult newly-diagnosed acute myeloid leukemia (AML) with or without allogeneic hematopoietic stem cell transplantation (Allo-HSCT).
Methods: We retrospectively analyzed 668 patients with newly-diagnosed AML (non-M3 type) in the Department of Hematology at Shanghai Changhai Hospital from January 2012 to December 2021. Based on different induction chemotherapy regimens, patients were categorized into an IA (idarubicin, IDA + cytarabine, Ara-C) (3 + 7, regimen) group (n = 303) and a DA (daunorubicin, DNR + cytarabine, Ara-C) (3 + 7, regimen) group (n = 365) with or without allo-HSCT. Minimal residual disease (MRD), complete response (CR), overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse effects (AE) were analyzed and compared. Characteristics significantly associated with overall or progression-free survival (OS or PFS) upon univariate analysis were subsequently included in a Cox proportional hazard model.
Results: This study used data from 668 AML patients. After induction therapy, the CR rate in the IA group was 70.63% and ORR was 79.87%, which were significantly higher than those in the DA group (with a CR rate of 56.99% and an ORR of 70.14%) (P = 0.0002 and P = 0.0035, respectively). There were no significant differences in drug safety between the two chemotherapy regimens used in IA and DA (P > 0.05). The recurrence rate was lower in patients with an MRD < 0.001 than in patients with an MRD ≥ 0.001. A continuous negative MRD during the period is significant because it is associated with prolonged OS and PFS of AML patients. Data from 100 patients in the two groups who underwent allo-HSCT were analyzed using univariate analysis and the Cox proportional hazards model. From the multivariate analysis, MRD was found to be the only independent predictor of OS (P = 0.042; HR 1; 95%CI 0.00-0.76).
Conclusion: In the treatment of adult AML patients, IA regimen is associated with a high CR rate and ORR rate and does not increase treatment-related toxicity. IA regimen prolongs OS and PFS in AML patients and reduces the likelihood of leukemia cells' subsequent infiltration into the central nervous system. There is a high correlation between the level of MRD after treatment and the patient's bone marrow recurrence. To obtain superior treatment effects for patients undergoing allo-HSCT, the MRD should be reduced to less than 0.001 before pretreatment. A negative MRD before allo-HSCT can prolong OS in patients with AML. We examined the clinical characteristics and outcomes of AML patients in China, finding novel information on prognostic factors and primary treatment of AML that may be applicable in routine clinical practice.
{"title":"Clinical features and outcomes of patients with acute myeloid leukemia: the single-center experience of 668 patients in China.","authors":"Jie Ding, Yang Su, Yinglu Ruan, Nan Li, Qianchao Meng, Jiabang Yang, Li Chen, Chi Liu","doi":"10.1080/16078454.2024.2310960","DOIUrl":"10.1080/16078454.2024.2310960","url":null,"abstract":"<p><strong>Objective: </strong>To investigate efficacy and prognostic factors in the treatment of adult newly-diagnosed acute myeloid leukemia (AML) with or without allogeneic hematopoietic stem cell transplantation (Allo-HSCT).</p><p><strong>Methods: </strong>We retrospectively analyzed 668 patients with newly-diagnosed AML (non-M3 type) in the Department of Hematology at Shanghai Changhai Hospital from January 2012 to December 2021. Based on different induction chemotherapy regimens, patients were categorized into an IA (idarubicin, IDA + cytarabine, Ara-C) (3 + 7, regimen) group (n = 303) and a DA (daunorubicin, DNR + cytarabine, Ara-C) (3 + 7, regimen) group (n = 365) with or without allo-HSCT. Minimal residual disease (MRD), complete response (CR), overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse effects (AE) were analyzed and compared. Characteristics significantly associated with overall or progression-free survival (OS or PFS) upon univariate analysis were subsequently included in a Cox proportional hazard model.</p><p><strong>Results: </strong>This study used data from 668 AML patients. After induction therapy, the CR rate in the IA group was 70.63% and ORR was 79.87%, which were significantly higher than those in the DA group (with a CR rate of 56.99% and an ORR of 70.14%) (<i>P</i> = 0.0002 and <i>P</i> = 0.0035, respectively). There were no significant differences in drug safety between the two chemotherapy regimens used in IA and DA (<i>P</i> > 0.05). The recurrence rate was lower in patients with an MRD < 0.001 than in patients with an MRD ≥ 0.001. A continuous negative MRD during the period is significant because it is associated with prolonged OS and PFS of AML patients. Data from 100 patients in the two groups who underwent allo-HSCT were analyzed using univariate analysis and the Cox proportional hazards model. From the multivariate analysis, MRD was found to be the only independent predictor of OS (<i>P</i> = 0.042; HR 1; 95%CI 0.00-0.76).</p><p><strong>Conclusion: </strong>In the treatment of adult AML patients, IA regimen is associated with a high CR rate and ORR rate and does not increase treatment-related toxicity. IA regimen prolongs OS and PFS in AML patients and reduces the likelihood of leukemia cells' subsequent infiltration into the central nervous system. There is a high correlation between the level of MRD after treatment and the patient's bone marrow recurrence. To obtain superior treatment effects for patients undergoing allo-HSCT, the MRD should be reduced to less than 0.001 before pretreatment. A negative MRD before allo-HSCT can prolong OS in patients with AML. We examined the clinical characteristics and outcomes of AML patients in China, finding novel information on prognostic factors and primary treatment of AML that may be applicable in routine clinical practice.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2310960"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-02-26DOI: 10.1080/16078454.2024.2320006
Hans Salwender, Niels Weinhold, Axel Benner, Kaya Miah, Maximilian Merz, Mathias Haenel, Christian Jehn, Elias Mai, Ekaterina Menis, Igor Blau, Christof Scheid, Dirk Hose, Anja Seckinger, Steffen Luntz, Britta Besemer, Markus Munder, Peter Brossart, Bertram Glass, Hans-Walter Lindemann, Katja Weisel, Christine Hanoun, Paul Schnitzler, Sarah Klemm, Hartmut Goldschmidt, Marc Raab, Ahmet Elmaagacli
Objectives: The seroprevalence of antibodies against Cytomegalovirus (CMV) is an established poor prognostic factor for patients receiving an allogeneic stem cell transplantation. However, the impact of CMV serology on outcome after autologous stem cell transplantation remains unknown.
Methods: Here, we analyzed the CMV immunoglobulin (Ig) serology of 446 newly-diagnosed multiple myeloma (MM) patients of the GMMG-MM5 phase III trial with a median follow-up of 58 months.
Results: CMV IgG and IgM positivity was seen in 51% and 6% of the patients, respectively. In multivariate analysis CMV IgG and CMV IgM serology show an age-depending effect for PFS. We identified positive CMV IgG/positive CMV IgM serology as an age-depending beneficial factor on PFS.
Discussion: Younger patients with a positive CMV IgG/positive CMV IgM serology experienced a favorable effect on PFS, whereas a positive CMV IgG/positive CMV IgM serology at older age has a disadvantageous effect on PFS.
{"title":"Cytomegalovirus immunoglobulin serology prevalence in patients with newly diagnosed multiple myeloma treated within the GMMG-MM5 phase III trial.","authors":"Hans Salwender, Niels Weinhold, Axel Benner, Kaya Miah, Maximilian Merz, Mathias Haenel, Christian Jehn, Elias Mai, Ekaterina Menis, Igor Blau, Christof Scheid, Dirk Hose, Anja Seckinger, Steffen Luntz, Britta Besemer, Markus Munder, Peter Brossart, Bertram Glass, Hans-Walter Lindemann, Katja Weisel, Christine Hanoun, Paul Schnitzler, Sarah Klemm, Hartmut Goldschmidt, Marc Raab, Ahmet Elmaagacli","doi":"10.1080/16078454.2024.2320006","DOIUrl":"https://doi.org/10.1080/16078454.2024.2320006","url":null,"abstract":"<p><strong>Objectives: </strong>The seroprevalence of antibodies against Cytomegalovirus (CMV) is an established poor prognostic factor for patients receiving an allogeneic stem cell transplantation. However, the impact of CMV serology on outcome after autologous stem cell transplantation remains unknown.</p><p><strong>Methods: </strong>Here, we analyzed the CMV immunoglobulin (Ig) serology of 446 newly-diagnosed multiple myeloma (MM) patients of the GMMG-MM5 phase III trial with a median follow-up of 58 months.</p><p><strong>Results: </strong>CMV IgG and IgM positivity was seen in 51% and 6% of the patients, respectively. In multivariate analysis CMV IgG and CMV IgM serology show an age-depending effect for PFS. We identified positive CMV IgG/positive CMV IgM serology as an age-depending beneficial factor on PFS.</p><p><strong>Discussion: </strong>Younger patients with a positive CMV IgG/positive CMV IgM serology experienced a favorable effect on PFS, whereas a positive CMV IgG/positive CMV IgM serology at older age has a disadvantageous effect on PFS.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2320006"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The involvement of N7-Methylguanine (m7G) RNA methylation regulators in the progression of different types of solid cancers in humans has been established. However, the specific impact of m7G-related genes on Acute myeloid leukemia (AML) remains uncertain. Our research aims to build a novel signature of M7Gs that could enhance our understanding of the molecular heterogeneity in leukemia.Methods: The RNA-seq and clinical data of patients with AML were acquired from the UCSC XENA website. Prognostic-related genes were selected using LASSO to construct a risk-scoring model. External datasets were utilized to validate the effectiveness of the model, and the mRNA expressions of candidate genes were measured using RT-qPCR.Results: A prognostic model was developed using a risk-scoring approach based on three candidate genes (IFIT5, EIF4E2, and LARP1) and their respective risk coefficients. Multivariate Cox regression analysis revealed a significant association between the risk score and overall survival (p<0.001). In both the experimental and validation cohorts, individuals classified as high risk exhibited a poorer prognosis. The 5-year area under the curve (AUC) was calculated as 0.715 for the TCGA-LAML cohort and 0.646 for GSE37642. Additionally, analysis using ssGSEA demonstrated that the high-risk group exhibited higher levels of immune cell infiltration compared to low-risk group. RT-qPCR results indicated that the expression levels of LARP1, EIF4E2 and IFIT5 were consistent with the results of the bioinformatic analysis.Conclusions: In summary, the m7G-related genes are potential prognostic biomarkers for patients with AML.
{"title":"A novel N7-Methylguanine-related gene signature for predicting prognosis in acute myeloid leukemia: bioinformatic analysis and experimental verification.","authors":"Ranran Zhao, Lulu Yang, Chenchen Liu, Ruoyu Jiang, Qianlei Huang, Qin Wang, Xiaojin Wu","doi":"10.1080/16078454.2024.2433905","DOIUrl":"https://doi.org/10.1080/16078454.2024.2433905","url":null,"abstract":"<p><p><b>Background:</b> The involvement of N7-Methylguanine (m7G) RNA methylation regulators in the progression of different types of solid cancers in humans has been established. However, the specific impact of m7G-related genes on Acute myeloid leukemia (AML) remains uncertain. Our research aims to build a novel signature of M7Gs that could enhance our understanding of the molecular heterogeneity in leukemia.<b>Methods:</b> The RNA-seq and clinical data of patients with AML were acquired from the UCSC XENA website. Prognostic-related genes were selected using LASSO to construct a risk-scoring model. External datasets were utilized to validate the effectiveness of the model, and the mRNA expressions of candidate genes were measured using RT-qPCR.<b>Results:</b> A prognostic model was developed using a risk-scoring approach based on three candidate genes (IFIT5, EIF4E2, and LARP1) and their respective risk coefficients. Multivariate Cox regression analysis revealed a significant association between the risk score and overall survival (<i>p</i><0.001). In both the experimental and validation cohorts, individuals classified as high risk exhibited a poorer prognosis. The 5-year area under the curve (AUC) was calculated as 0.715 for the TCGA-LAML cohort and 0.646 for GSE37642. Additionally, analysis using ssGSEA demonstrated that the high-risk group exhibited higher levels of immune cell infiltration compared to low-risk group. RT-qPCR results indicated that the expression levels of LARP1, EIF4E2 and IFIT5 were consistent with the results of the bioinformatic analysis.<b>Conclusions:</b> In summary, the m7G-related genes are potential prognostic biomarkers for patients with AML.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2433905"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-09-09DOI: 10.1080/16078454.2024.2399375
Meixiao Shen, Xiansheng Luo, Cuiyun Wu, Juan Wang, Zhiming Wang, Meiqing Lei
Background: Pernicious anemia (PA) is believed to be highly prevalent in Western countries but has rarely been reported in China. The study explores whether PA, an autoimmune disease, is an uncommon cause of cobalamin (vitamin B12) deficiency anemia in China.
Methods: Clinical and hematological data were collected from 90 cobalamin deficiency-caused megaloblastic anemia (MA) patients between July 2014 and December 2021. Through anti-intrinsic factor antibody (IFA) and anti-parietal cell antibody (PCA) testing, PA was distinguished from other causes of cobalamin deficiency leading to MA. Meanwhile, 30 healthy controls (HCs) were included to estimate the positive rates of IFA and PCA.
Results: Of the 30 HCs, only one tested positive for IFA, and all 30 tested negative for PCA. Among the 90 patients with cobalamin deficiency-caused MA, 76.7% were positive for IFA, and 47.8% were positive for PCA; a total of 76 patients (84.4%) were diagnosed with PA. The mean follow-up time was 41.0 ± 16.3 months. During the follow-up period, no case relapsed among the continuous cobalamin-supply treatment patients, while 24.4% of patients relapsed due to the interruption of maintenance cobalamin-supplement therapy (the median recurrence time was 54.0 ± 17.7 months).
Conclusions: The proportion of PA in cobalamin deficiency-caused MA patients in Hainan province was higher than 80%, which was more common than expected. Therefore, screening for IFA, PCA, endoscopic biopsy, and thyroid-related parameters are recommended for all cobalamin deficiency-caused MA patients. Furthermore, maintenance cobalamin-supplement therapy is important for PA patients.
背景:恶性贫血(PA)被认为在西方国家非常普遍,但在中国却鲜有报道。本研究探讨了恶性贫血这种自身免疫性疾病是否是中国钴胺素(维生素 B12)缺乏性贫血的一个不常见病因:方法:研究收集了2014年7月至2021年12月期间90例由钴胺素缺乏引起的巨幼细胞性贫血(MA)患者的临床和血液学数据。通过抗内因子抗体(IFA)和抗顶叶细胞抗体(PCA)检测,将PA与其他原因导致的钴胺素缺乏性巨幼红细胞性贫血区分开来。同时,还纳入了30名健康对照者(HCs),以估算IFA和PCA的阳性率:结果:在 30 名健康对照者中,只有一人的 IFA 检测呈阳性,30 人的 PCA 检测均呈阴性。在 90 名钴胺素缺乏导致的 MA 患者中,76.7% 的患者 IFA 阳性,47.8% 的患者 PCA 阳性;共有 76 名患者(84.4%)被诊断为 PA。平均随访时间为(41.0 ± 16.3)个月。在随访期间,持续服用钴胺素治疗的患者无一例复发,而24.4%的患者因中断钴胺素维持治疗而复发(中位复发时间为(54.0 ± 17.7)个月):结论:海南省钴胺素缺乏导致的MA患者中PA的比例高于80%,比预期的更为常见。因此,建议对所有钴胺素缺乏引起的 MA 患者进行 IFA、PCA、内镜活检和甲状腺相关指标筛查。此外,钴胺素补充剂的维持治疗对PA患者也很重要。
{"title":"Pernicious anemia is a common cause of cobalamin deficiency-caused megaloblastic anemia in Hainan, China.","authors":"Meixiao Shen, Xiansheng Luo, Cuiyun Wu, Juan Wang, Zhiming Wang, Meiqing Lei","doi":"10.1080/16078454.2024.2399375","DOIUrl":"https://doi.org/10.1080/16078454.2024.2399375","url":null,"abstract":"<p><strong>Background: </strong>Pernicious anemia (PA) is believed to be highly prevalent in Western countries but has rarely been reported in China. The study explores whether PA, an autoimmune disease, is an uncommon cause of cobalamin (vitamin B12) deficiency anemia in China.</p><p><strong>Methods: </strong>Clinical and hematological data were collected from 90 cobalamin deficiency-caused megaloblastic anemia (MA) patients between July 2014 and December 2021. Through anti-intrinsic factor antibody (IFA) and anti-parietal cell antibody (PCA) testing, PA was distinguished from other causes of cobalamin deficiency leading to MA. Meanwhile, 30 healthy controls (HCs) were included to estimate the positive rates of IFA and PCA.</p><p><strong>Results: </strong>Of the 30 HCs, only one tested positive for IFA, and all 30 tested negative for PCA. Among the 90 patients with cobalamin deficiency-caused MA, 76.7% were positive for IFA, and 47.8% were positive for PCA; a total of 76 patients (84.4%) were diagnosed with PA. The mean follow-up time was 41.0 ± 16.3 months. During the follow-up period, no case relapsed among the continuous cobalamin-supply treatment patients, while 24.4% of patients relapsed due to the interruption of maintenance cobalamin-supplement therapy (the median recurrence time was 54.0 ± 17.7 months).</p><p><strong>Conclusions: </strong>The proportion of PA in cobalamin deficiency-caused MA patients in Hainan province was higher than 80%, which was more common than expected. Therefore, screening for IFA, PCA, endoscopic biopsy, and thyroid-related parameters are recommended for all cobalamin deficiency-caused MA patients. Furthermore, maintenance cobalamin-supplement therapy is important for PA patients.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2399375"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The relationship between different types of autoimmune diseases and myelodysplastic syndrome (MDS) is inconclusive. Therefore, we employed Mendelian randomization (MR) to examine whether genetically predicted susceptibility to ten autoimmune diseases is associated with the risk of MDS.Methods: Single nucleotide polymorphisms (SNPs) significantly associated with 10 autoimmune diseases were extracted from the summary statistics of European genome-wide association studies (GWAS). A two-sample MR analysis was performed using summary-level statistics sourced from GWAS datasets. Inverse-variance weighting (IVW), MR-Egger, and weighted median (WM) were further supported by several sensitivity analyses.Results: Four autoimmune diseases showed genetical predisposition to MDS: rheumatoid arthritis (OR = 1.186,95% CI = 1.028-1.367, P = 0.019), multiple sclerosis (OR = 1.247, 95% CI = 1.013-1.534, P = 0.037), myasthenia gravis (OR = 1.326,95% CI = 1.010-1.742, P = 0.042), and Hashimoto thyroiditis(OR = 1.519,95% CI = 1.008-2.290, P = 0.046). Nevertheless, no similar causal relationship was found between the remaining seven autoimmune diseases and MDS. The accuracy and robustness of these findings were confirmed by sensitivity tests.Conclusions: We are the first to use MR analysis to explore the relationship between autoimmune diseases and MDS. The mechanism needs to be further explored.
背景:不同类型的自身免疫性疾病与骨髓增生异常综合征(MDS)之间的关系尚无定论。因此,我们采用孟德尔随机化法(MR)研究了遗传学预测的十种自身免疫性疾病的易感性是否与 MDS 风险相关:从欧洲全基因组关联研究(GWAS)的汇总统计中提取了与10种自身免疫性疾病显著相关的单核苷酸多态性(SNPs)。使用来自 GWAS 数据集的摘要级统计数据进行了双样本 MR 分析。反方差加权(IVW)、MR-Egger 和加权中位数(WM)通过几种敏感性分析得到了进一步支持:结果:四种自身免疫性疾病显示出对 MDS 的遗传易感性:类风湿性关节炎(OR = 1.186,95% CI = 1.028-1.367,P = 0.019)、多发性硬化症(OR = 1.247, 95% CI = 1.013-1.534, P = 0.037)、重症肌无力(OR = 1.326,95% CI = 1.010-1.742, P = 0.042)和桥本氏甲状腺炎(OR = 1.519,95% CI = 1.008-2.290, P = 0.046)。然而,在其余七种自身免疫性疾病与 MDS 之间并没有发现类似的因果关系。这些发现的准确性和稳健性已通过敏感性测试得到证实:我们首次使用磁共振分析来探讨自身免疫性疾病与 MDS 之间的关系。其机制有待进一步探讨。
{"title":"Association between autoimmune diseases and myelodysplastic syndrome:a Mendelian randomization study.","authors":"Zhengyang Miao, Wenwei Zhu, Yongming Zhou, Hailin Chen","doi":"10.1080/16078454.2024.2433799","DOIUrl":"10.1080/16078454.2024.2433799","url":null,"abstract":"<p><p><b>Background</b>: The relationship between different types of autoimmune diseases and myelodysplastic syndrome (MDS) is inconclusive. Therefore, we employed Mendelian randomization (MR) to examine whether genetically predicted susceptibility to ten autoimmune diseases is associated with the risk of MDS.<b>Methods:</b> Single nucleotide polymorphisms (SNPs) significantly associated with 10 autoimmune diseases were extracted from the summary statistics of European genome-wide association studies (GWAS). A two-sample MR analysis was performed using summary-level statistics sourced from GWAS datasets. Inverse-variance weighting (IVW), MR-Egger, and weighted median (WM) were further supported by several sensitivity analyses.<b>Results:</b> Four autoimmune diseases showed genetical predisposition to MDS: rheumatoid arthritis (OR = 1.186,95% CI = 1.028-1.367, <i>P</i> = 0.019), multiple sclerosis (OR = 1.247, 95% CI = 1.013-1.534, <i>P</i> = 0.037), myasthenia gravis (OR = 1.326,95% CI = 1.010-1.742, <i>P</i> = 0.042), and Hashimoto thyroiditis(OR = 1.519,95% CI = 1.008-2.290, <i>P</i> = 0.046). Nevertheless, no similar causal relationship was found between the remaining seven autoimmune diseases and MDS. The accuracy and robustness of these findings were confirmed by sensitivity tests.<b>Conclusions:</b> We are the first to use MR analysis to explore the relationship between autoimmune diseases and MDS. The mechanism needs to be further explored.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2433799"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142728074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: This study analyzed the relationship between bone marrow microvessel density (MVD) and the expression of four miRNAs with chronic myelogenous leukemia (CML) resistance after tyrosine kinase inhibitor (TKI) treatment.
Methods: 234 CML patients were divided into resistance and non-resistance groups in terms of the results of the 5-year follow-up. Patients were divided into the Optimum response group and the Warning/Failure group based on TKI response. MVD was determined by immunohistochemistry, and the expression levels of four miRNAs (miR-106a, miR-155, miR-146a, and miR-340) in bone marrow biopsy specimens were examined by qPCR. We evaluated the association of MVD with four miRNAs and them predictive value for CML resistance after TKI treatment.
Results: The MVD and the levels of miR-106a, miR-155, and miR-146a were significantly higher while the miR-340 level was lower in the resistance group than the non-resistance group. Besides, MVD had a significant correlation with the levels of miR-340 and miR-155. According to the results of survival analysis, MVD as well as miR-340 and miR-155 levels were observably correlated with 5-year survival of patients without TKI resistance. The results of the ROC curve indicated that the MVD, miR-106a, miR-340, and miR-155 had good predictive accuracy for CML resistance after TKI treatment. As for the results of multivariate analysis, disease stage, risk level (high risk), high MVD, low miR-340 expression, and high miR-155 expression were all independent risk factors for CML resistance.
Conclusion: MVD and the expression of miR-340 and miR-155 are closely associated with CML resistance after TKI treatment.
{"title":"Correlation analysis of bone marrow microvessel density and miRNA expression on drug resistance in patients with chronic myelogenous leukemia after tyrosine kinase inhibitor treatment.","authors":"Yi-Gang Guo, Lu-Lu Zhang, Ping Hu, Zhang-Zhi Li, Rui-Bo Zhang, Xi Lv, Qiong Yi, Ling-Bo Zhan, Xue-Lian Feng","doi":"10.1080/16078454.2024.2304488","DOIUrl":"10.1080/16078454.2024.2304488","url":null,"abstract":"<p><strong>Objective: </strong>This study analyzed the relationship between bone marrow microvessel density (MVD) and the expression of four miRNAs with chronic myelogenous leukemia (CML) resistance after tyrosine kinase inhibitor (TKI) treatment.</p><p><strong>Methods: </strong>234 CML patients were divided into resistance and non-resistance groups in terms of the results of the 5-year follow-up. Patients were divided into the Optimum response group and the Warning/Failure group based on TKI response. MVD was determined by immunohistochemistry, and the expression levels of four miRNAs (miR-106a, miR-155, miR-146a, and miR-340) in bone marrow biopsy specimens were examined by qPCR. We evaluated the association of MVD with four miRNAs and them predictive value for CML resistance after TKI treatment.</p><p><strong>Results: </strong>The MVD and the levels of miR-106a, miR-155, and miR-146a were significantly higher while the miR-340 level was lower in the resistance group than the non-resistance group. Besides, MVD had a significant correlation with the levels of miR-340 and miR-155. According to the results of survival analysis, MVD as well as miR-340 and miR-155 levels were observably correlated with 5-year survival of patients without TKI resistance. The results of the ROC curve indicated that the MVD, miR-106a, miR-340, and miR-155 had good predictive accuracy for CML resistance after TKI treatment. As for the results of multivariate analysis, disease stage, risk level (high risk), high MVD, low miR-340 expression, and high miR-155 expression were all independent risk factors for CML resistance.</p><p><strong>Conclusion: </strong>MVD and the expression of miR-340 and miR-155 are closely associated with CML resistance after TKI treatment.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2304488"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}