Invasive fungal diseases (IFDs) are major and lethal infectious complications for patients with neutropenia after chemotherapy. Prophylaxis with intravenous and oral suspended itraconazole (200 mg Q12h intravenously × 2 days followed by 5 mg/kg·d orally in twice) or oral suspension of posaconazole (200 mg Q8h) was administered for preventing IFDs. The only 2 episodes of proven IFDs were not included after propensity-score matching (PSM), while the incidence of possible IFDs was 8.2% (9/110) in itraconazole group and 1.8% (2/110) in posaconazole group, respectively (P = .030). In clinical failure analysis, the failure rate of posaconazole group was lower as compared to the itraconazole group (2.7% vs 10.9%, P = .016). Both intravenous-oral itraconazole and posaconazole suspension are effective in preventing IFDs, while posaconazole suspension seems more tolerable.
侵袭性真菌病(IFDs)是中性粒细胞减少患者化疗后主要的致死性感染性并发症。预防方法:静脉滴注和口服伊曲康唑悬浮液(200 mg Q12h静脉滴注× 2天,随后5 mg/kg·d口服2次)或泊沙康唑口服悬浮液(200 mg Q8h)。经倾向评分匹配(PSM)后,仅有2例确诊IFDs未被纳入,而伊曲康唑组和泊沙康唑组的可能IFDs发生率分别为8.2%(9/110)和1.8% (2/110)(P = 0.030)。在临床失败分析中,泊沙康唑组的失败率低于伊曲康唑组(2.7% vs 10.9%, P = 0.016)。静脉-口服伊曲康唑和泊沙康唑混悬液均可有效预防ifd,泊沙康唑混悬液的耐受性更强。
{"title":"Intravenous-oral itraconazole versus oral posaconazole in preventing invasive fungal diseases for acute leukemia patients.","authors":"Li Liu, Xiaolei Pei, Runzhi Ma, Yi He, Rongli Zhang, Jialin Wei, Qiaoling Ma, Weihua Zhai, Aiming Pang, Erlie Jiang, Mingzhe Han, Donglin Yang, Sizhou Feng","doi":"10.1097/BS9.0000000000000155","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000155","url":null,"abstract":"<p><p>Invasive fungal diseases (IFDs) are major and lethal infectious complications for patients with neutropenia after chemotherapy. Prophylaxis with intravenous and oral suspended itraconazole (200 mg Q12h intravenously × 2 days followed by 5 mg/kg·d orally in twice) or oral suspension of posaconazole (200 mg Q8h) was administered for preventing IFDs. The only 2 episodes of proven IFDs were not included after propensity-score matching (PSM), while the incidence of possible IFDs was 8.2% (9/110) in itraconazole group and 1.8% (2/110) in posaconazole group, respectively (<i>P</i> = .030). In clinical failure analysis, the failure rate of posaconazole group was lower as compared to the itraconazole group (2.7% vs 10.9%, <i>P</i> = .016). Both intravenous-oral itraconazole and posaconazole suspension are effective in preventing IFDs, while posaconazole suspension seems more tolerable.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9525569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-01DOI: 10.1097/BS9.0000000000000145
Yong-Xin Ru, Shu-Xu Dong, Jing Liu, Brian Eyden
Giant inclusions and Auer bodies in promyeloblasts were investigated in a study which included transmission electron microscopy (TEM) for morphology and ultrastructural cytochemistry for myeloperoxidase in 10 patients with acute promyelocytic leukemia (APL). Ultrastructural cytochemistry demonstrated positive myeloperoxidase reactivity in giant inclusions, expanded rER cisternae, Auer bodies and primary granules. TEM revealed that giant inclusions were adorned by degenerated rER membrane, some of them sharing features with Auer bodies. We hypothesize a novel origin for Auer body development in promyeloblasts of APL, namely that they originate from peroxidase-positive and expanded rER cisternae, and that primary granules were directly released from these expanded rER elements, bypassing the Golgi apparatus.
{"title":"Development of Auer bodies from giant inclusions associated with rough endoplasmic reticulum in acute promyelocytic leukemia.","authors":"Yong-Xin Ru, Shu-Xu Dong, Jing Liu, Brian Eyden","doi":"10.1097/BS9.0000000000000145","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000145","url":null,"abstract":"<p><p>Giant inclusions and Auer bodies in promyeloblasts were investigated in a study which included transmission electron microscopy (TEM) for morphology and ultrastructural cytochemistry for myeloperoxidase in 10 patients with acute promyelocytic leukemia (APL). Ultrastructural cytochemistry demonstrated positive myeloperoxidase reactivity in giant inclusions, expanded rER cisternae, Auer bodies and primary granules. TEM revealed that giant inclusions were adorned by degenerated rER membrane, some of them sharing features with Auer bodies. We hypothesize a novel origin for Auer body development in promyeloblasts of APL, namely that they originate from peroxidase-positive and expanded rER cisternae, and that primary granules were directly released from these expanded rER elements, bypassing the Golgi apparatus.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10299795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-01DOI: 10.1097/BS9.0000000000000150
Jianmin Wang, Dan Yang
In a recent issue of Lancet Haematology , Xue et al 1 reported an adeno-associated virus (AAV)-based gene therapy in 10 patients with hemophilia B (HB) from China. BBM-H901, a novel vector comprised of an engineered liver-tropic AAV cap- sid (AAV843), synthesized liver-specific promoter and CpG reduced factor IX (FIX) Padua coding sequence, was infused in 10 patients (baseline FIX coagulation activity [FIX:C] were less than 2 IU/dL) after 1 week of prophylactic prednisone pretreat- ment (1 mg/kg per day). After a median follow-up of 58 weeks, mean FIX:C reached 36.9 ± 20·5 IU/dL. No FIX inhibitors or serious adverse events were observed. All patients developed high titer neutralizing antibodies against vector capsid. The concentrations of alanine aminotransferase and aspartate aminotransferase in plasma were below the upper limit of normal range in 8 patients. No FIX concentrate infusion was needed after gene therapy for these patients. This is a huge step forward in the treatment of HB in China.
{"title":"Big stride in gene therapy for hemophilia B in China.","authors":"Jianmin Wang, Dan Yang","doi":"10.1097/BS9.0000000000000150","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000150","url":null,"abstract":"In a recent issue of Lancet Haematology , Xue et al 1 reported an adeno-associated virus (AAV)-based gene therapy in 10 patients with hemophilia B (HB) from China. BBM-H901, a novel vector comprised of an engineered liver-tropic AAV cap- sid (AAV843), synthesized liver-specific promoter and CpG reduced factor IX (FIX) Padua coding sequence, was infused in 10 patients (baseline FIX coagulation activity [FIX:C] were less than 2 IU/dL) after 1 week of prophylactic prednisone pretreat- ment (1 mg/kg per day). After a median follow-up of 58 weeks, mean FIX:C reached 36.9 ± 20·5 IU/dL. No FIX inhibitors or serious adverse events were observed. All patients developed high titer neutralizing antibodies against vector capsid. The concentrations of alanine aminotransferase and aspartate aminotransferase in plasma were below the upper limit of normal range in 8 patients. No FIX concentrate infusion was needed after gene therapy for these patients. This is a huge step forward in the treatment of HB in China.","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9530768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-01DOI: 10.1097/BS9.0000000000000154
Tsvee Lapidot
The bone marrow (BM) contains the major reservoir of imma- ture and maturing hematopoietic and immune cells throughout adult life while also harboring most hematopoietic stem and progenitor cells (HSPCs). BM-retained hematopoietic stem cells (HSCs) are mostly maintained in a quiescent, non-motile mode. A small fraction of BM-retained HSPC daily proliferate, differ-entiate, and migrate to the circulation, to replenish the blood with new immature and maturing blood and (all) immune (both myeloid and lymphoid) cells with a finite life span. 1 The anti-co-agulation and anti-inflammatory receptor EPCR is also func- tionally expressed by primitive BM-retained HSCs which are endowed with the highest competitive long-term repopulation potential (LT-HSC). Only BM-retained, quiescent EPCR-positive LT-HSCs are protected from DNA damaging insults includ- ing clinical chemotherapy and radiation treatments. Primitive EPCR-positive LT-HSC chemotherapy resistance requires the CXCL12-CXCR4 axis that also regulates HSC quiescence, cell cycle, and directional migration as well as the aPC/EPCR/PAR1 axis. 2,3 The chemokine CXCL12 is highly expressed by many BM endothelial and stromal cells types including HSC niche supporting osteoprogenitor cells termed CXCL12 abundant reticular cells (CAR cells), while primitive EPCR-positive fetal liver and adult BM HSC functionally express its major receptor CXCR4. 4 Most functional HSC studies involve mice experimental pre- clinical models as well as results obtained from clinical BM transplantation protocols. During fetal development, HSCs migrate from the fetal liver to the fetal BM and spleen for their lodgment
{"title":"Timing and regulation of hematopoietic stem cell colonization of the human fetal bone marrow by endothelial and CAR stromal cells during pregnancy.","authors":"Tsvee Lapidot","doi":"10.1097/BS9.0000000000000154","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000154","url":null,"abstract":"The bone marrow (BM) contains the major reservoir of imma- ture and maturing hematopoietic and immune cells throughout adult life while also harboring most hematopoietic stem and progenitor cells (HSPCs). BM-retained hematopoietic stem cells (HSCs) are mostly maintained in a quiescent, non-motile mode. A small fraction of BM-retained HSPC daily proliferate, differ-entiate, and migrate to the circulation, to replenish the blood with new immature and maturing blood and (all) immune (both myeloid and lymphoid) cells with a finite life span. 1 The anti-co-agulation and anti-inflammatory receptor EPCR is also func- tionally expressed by primitive BM-retained HSCs which are endowed with the highest competitive long-term repopulation potential (LT-HSC). Only BM-retained, quiescent EPCR-positive LT-HSCs are protected from DNA damaging insults includ- ing clinical chemotherapy and radiation treatments. Primitive EPCR-positive LT-HSC chemotherapy resistance requires the CXCL12-CXCR4 axis that also regulates HSC quiescence, cell cycle, and directional migration as well as the aPC/EPCR/PAR1 axis. 2,3 The chemokine CXCL12 is highly expressed by many BM endothelial and stromal cells types including HSC niche supporting osteoprogenitor cells termed CXCL12 abundant reticular cells (CAR cells), while primitive EPCR-positive fetal liver and adult BM HSC functionally express its major receptor CXCR4. 4 Most functional HSC studies involve mice experimental pre- clinical models as well as results obtained from clinical BM transplantation protocols. During fetal development, HSCs migrate from the fetal liver to the fetal BM and spleen for their lodgment","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/4e/bs9-5-140.PMC10205243.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9530770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-01DOI: 10.1097/BS9.0000000000000149
Yu-Jie Zhou, Guoli Li, Jiyin Wang, Mengyuan Liu, Zihan Wang, Yu Song, Xulong Zhang, Xi Wang
Programmed death-ligand 1 (PD-L1), expressed on the surface of tumor cells, can bind to programmed cell death-1 (PD-1) on T cells. The interaction of PD-1 and PD-L1 can inhibit T-cell responses by decreasing T-cell activity and accelerating their apoptosis. Various cancers express high levels of PD-L1 and exploit PD-L1/PD-1 signaling to evade T-cell immunity, and immunotherapies targeting the PD-1/PD-L1 axis have been shown to exert remarkable anti-tumor effects; however, not all tumor patients benefit from these therapies. Therefore, study of the mechanisms regulating PD-L1 expression are imperative. In this review, we explore regulation of PD-L1 expression in the contexts of gene transcription, signaling pathways, histone modification and remodeling, microRNAs, long noncoding RNAs, and post-translational modification. Current developments in studies of agents that block PD-L1 and correlations between immunotherapies targeting PD-1/PD-L1 and PD-L1 expression are also summarized. Our review will assist in understanding of PD-L1 expression regulation and discusses the implications of reported findings in cancer diagnosis and immunotherapy.
{"title":"PD-L1: expression regulation.","authors":"Yu-Jie Zhou, Guoli Li, Jiyin Wang, Mengyuan Liu, Zihan Wang, Yu Song, Xulong Zhang, Xi Wang","doi":"10.1097/BS9.0000000000000149","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000149","url":null,"abstract":"<p><p>Programmed death-ligand 1 (PD-L1), expressed on the surface of tumor cells, can bind to programmed cell death-1 (PD-1) on T cells. The interaction of PD-1 and PD-L1 can inhibit T-cell responses by decreasing T-cell activity and accelerating their apoptosis. Various cancers express high levels of PD-L1 and exploit PD-L1/PD-1 signaling to evade T-cell immunity, and immunotherapies targeting the PD-1/PD-L1 axis have been shown to exert remarkable anti-tumor effects; however, not all tumor patients benefit from these therapies. Therefore, study of the mechanisms regulating PD-L1 expression are imperative. In this review, we explore regulation of PD-L1 expression in the contexts of gene transcription, signaling pathways, histone modification and remodeling, microRNAs, long noncoding RNAs, and post-translational modification. Current developments in studies of agents that block PD-L1 and correlations between immunotherapies targeting PD-1/PD-L1 and PD-L1 expression are also summarized. Our review will assist in understanding of PD-L1 expression regulation and discusses the implications of reported findings in cancer diagnosis and immunotherapy.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9518329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-01DOI: 10.1097/BS9.0000000000000153
Yan Hui, Shuxin Li, Junping Zhang, Bingcheng Liu, Yingchang Mi, Hui Wei, Jianxiang Wang
Patients with double-mutated CEBPA (CEBPAdm) AML were stratified into favorable risk group, however, few studies have investigated the heterogeneity of different CEBPAdm types in detail. In this study, we analyzed 2211 newly diagnosed AML and identified CEBPAdm in 10.8% of the patients. Within the CEBPAdm cohort, 225 of 239 patients (94.14%) presented with bZIP region mutations (CEBPAdmbZIP) while 14 of 239 patients (5.86%) without bZIP region mutation (CEBPAdmnonbZIP). Analysis of the accompanied molecular mutations showed statistically different incidences of GATA2 mutations between the CEBPAdmbZIP group and the CEBPAdmnonbZIP group (30.29% vs 0%). In the analysis of outcomes, patients with CEBPAdmnonbZIP were associated with shorter overall survival (OS) censored at hematopoietic stem cell transplantation (HSCT) during CR1 compared to those with CEBPAdmbZIP (hazard ratio (HR) = 3.132, 95% confidence interval (CI) = 1.229-7.979, P = .017). Refractory or relapsed AML (R/RAML) patients with CEBPAdmnonbZIP were associated with shorter OS compared to those with CEBPAdmbZIP (HR = 2.881, 95% CI = 1.021-8.131, P = .046). Taken together, AML with CEBPAdmbZIP and CEBPAdmnonbZIP showed different outcomes and might be regarded as distinctive AML entities.
双突变CEBPA (CEBPAdm) AML患者被划分为有利风险组,但很少有研究详细探讨不同类型CEBPAdm的异质性。在这项研究中,我们分析了2211例新诊断的AML,在10.8%的患者中发现了CEBPAdm。在CEBPAdm队列中,239例患者中有225例(94.14%)出现bZIP区域突变(CEBPAdmbZIP), 239例患者中有14例(5.86%)未出现bZIP区域突变(CEBPAdmnonbZIP)。伴随分子突变分析显示,CEBPAdmbZIP组和CEBPAdmnonbZIP组的GATA2突变发生率有统计学差异(30.29% vs 0%)。在结果分析中,与CEBPAdmbZIP患者相比,CEBPAdmnonbZIP患者在CR1期间造血干细胞移植(HSCT)中总生存期(OS)更短(风险比(HR) = 3.132, 95%可信区间(CI) = 1.229-7.979, P = 0.017)。与患有CEBPAdmnonbZIP的患者相比,患有CEBPAdmbZIP的难治性或复发性AML (R/RAML)患者的生存期较短(HR = 2.881, 95% CI = 1.021-8.131, P = 0.046)。合并CEBPAdmbZIP和CEBPAdmnonbZIP的AML表现出不同的结果,可能被视为不同的AML实体。
{"title":"Heterogeneity analysis of the <i>CEBPA</i>dm AML based on bZIP region mutations.","authors":"Yan Hui, Shuxin Li, Junping Zhang, Bingcheng Liu, Yingchang Mi, Hui Wei, Jianxiang Wang","doi":"10.1097/BS9.0000000000000153","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000153","url":null,"abstract":"<p><p>Patients with double-mutated <i>CEBPA</i> (<i>CEBPA</i>dm) AML were stratified into favorable risk group, however, few studies have investigated the heterogeneity of different <i>CEBPA</i>dm types in detail. In this study, we analyzed 2211 newly diagnosed AML and identified <i>CEBPA</i>dm in 10.8% of the patients. Within the <i>CEBPA</i>dm cohort, 225 of 239 patients (94.14%) presented with bZIP region mutations (<i>CEBPA</i>dmbZIP) while 14 of 239 patients (5.86%) without bZIP region mutation (<i>CEBPA</i>dmnonbZIP). Analysis of the accompanied molecular mutations showed statistically different incidences of GATA2 mutations between the <i>CEBPA</i>dmbZIP group and the <i>CEBPA</i>dmnonbZIP group (30.29% vs 0%). In the analysis of outcomes, patients with <i>CEBPA</i>dmnonbZIP were associated with shorter overall survival (OS) censored at hematopoietic stem cell transplantation (HSCT) during CR1 compared to those with <i>CEBPA</i>dmbZIP (hazard ratio (HR) = 3.132, 95% confidence interval (CI) = 1.229-7.979, <i>P</i> = .017). Refractory or relapsed AML (R/RAML) patients with <i>CEBPA</i>dmnonbZIP were associated with shorter OS compared to those with <i>CEBPA</i>dmbZIP (HR = 2.881, 95% CI = 1.021-8.131, <i>P</i> = .046). Taken together, AML with <i>CEBPA</i>dmbZIP and <i>CEBPA</i>dmnonbZIP showed different outcomes and might be regarded as distinctive AML entities.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9896944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rothmund-Thomson syndrome (RTS) is a rare autosomal-recessive disorder with clinical features consisting of rash, poikiloderma, sparse hair, short stature, juvenile cataracts, skeletal abnormalities, and cancer predisposition. Genetic studies involving detection of pathogenic RECQL4 variants provide the diagnostic certitude. Osteosarcoma was found in two-thirds RECQL4-mutated RTS patients, while hematological malignancies were rarely reported. The variant diversity of RECQL4 gene has not been fully identified and mutations associated with hematologic malignancies are not well described. In this study, we presented a pedigree of RTS from a Chinese family, among which the proband was diagnosed with de novo myelodysplastic syndrome (MDS). Comprehensive medical examination and chromosome karyotyping were performed on the proband. Whole exome sequencing (WES) was performed on the proband, his sister and his mother. The familial cosegregation of sequence variants derived from WES was conducted by polymerase chain reaction-based Sanger sequencing. Structures of candidate RECQL4 mutants were done by in silico analysis to assess pathogenicity. Three novel RECQL4 germline variants, including c.T274C, c.G3014A, and c.G801C, were identified by WES and validated by Sanger sequencing. Prediction of conformation indicated that the structural stability of human RECQL4 protein was largely affected with these variants. The co-occurring U2AF1 p.S34F and TP53 p.Y220C mutations might contribute to the development of MDS. Our study expands the mutational spectrum of RECQL4 and provides underlying molecular mechanism for the development of MDS in RTS patients.
{"title":"De novo myelodysplastic syndrome in a Rothmund-Thomson Syndrome patient with novel pathogenic <i>RECQL4</i> variants.","authors":"Chuanhe Jiang, Hao Zhang, Chuxian Zhao, Luxiang Wang, Xiaoxia Hu, Zengkai Pan","doi":"10.1097/BS9.0000000000000152","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000152","url":null,"abstract":"<p><p>Rothmund-Thomson syndrome (RTS) is a rare autosomal-recessive disorder with clinical features consisting of rash, poikiloderma, sparse hair, short stature, juvenile cataracts, skeletal abnormalities, and cancer predisposition. Genetic studies involving detection of pathogenic <i>RECQL4</i> variants provide the diagnostic certitude. Osteosarcoma was found in two-thirds <i>RECQL4</i>-mutated RTS patients, while hematological malignancies were rarely reported. The variant diversity of <i>RECQL4</i> gene has not been fully identified and mutations associated with hematologic malignancies are not well described. In this study, we presented a pedigree of RTS from a Chinese family, among which the proband was diagnosed with de novo myelodysplastic syndrome (MDS). Comprehensive medical examination and chromosome karyotyping were performed on the proband. Whole exome sequencing (WES) was performed on the proband, his sister and his mother. The familial cosegregation of sequence variants derived from WES was conducted by polymerase chain reaction-based Sanger sequencing. Structures of candidate RECQL4 mutants were done by in silico analysis to assess pathogenicity. Three novel <i>RECQL4</i> germline variants, including c.T274C, c.G3014A, and c.G801C, were identified by WES and validated by Sanger sequencing. Prediction of conformation indicated that the structural stability of human RECQL4 protein was largely affected with these variants. The co-occurring <i>U2AF1</i> p.S34F and <i>TP53</i> p.Y220C mutations might contribute to the development of MDS. Our study expands the mutational spectrum of <i>RECQL4</i> and provides underlying molecular mechanism for the development of MDS in RTS patients.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/7a/bs9-5-125.PMC10205365.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9530771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-01DOI: 10.1097/BS9.0000000000000158
Chang Xu, Ting Lu, Xue Lv, Tao Cheng, Hui Cheng
Leukemia stem cells in acute myeloid leukemia (AML) can persist within unique bone marrow niches similar to those of healthy hematopoietic stem cells and resist chemotherapy. In the context of AML, endothelial cells (ECs) are crucial components of these niches that appear to promote malignant expansion despite treatment. To better understand these interactions, we developed a real-time cell cycle-tracking mouse model of AML (Fucci-MA9) with an aim of unraveling why quiescent leukemia cells are more resistant to chemotherapy than cycling cells and proliferate during disease relapse. We found that quiescent leukemia cells were more prone to escape chemotherapy than cycling cells, leading to relapse and proliferation. Importantly, post-chemotherapy resting leukemia cells tended to localize closer to blood vessels. Mechanistically, after chemotherapy, resting leukemia cells interacted with ECs, promoting their adhesion and anti-apoptotic capacity. Further, expression analysis of ECs and leukemia cells during AML, after chemotherapy, and after relapse revealed the potential of suppressing the post-chemotherapy inflammatory response to regulate the functions of leukemia cells and ECs. These findings highlight the role of leukemia cells in evading chemotherapy by seeking refuge near blood vessels and provide important insights and directions for future AML research and treatment.
{"title":"Role of the bone marrow vascular niche in chemotherapy for MLL-AF9-induced acute myeloid leukemia.","authors":"Chang Xu, Ting Lu, Xue Lv, Tao Cheng, Hui Cheng","doi":"10.1097/BS9.0000000000000158","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000158","url":null,"abstract":"<p><p>Leukemia stem cells in acute myeloid leukemia (AML) can persist within unique bone marrow niches similar to those of healthy hematopoietic stem cells and resist chemotherapy. In the context of AML, endothelial cells (ECs) are crucial components of these niches that appear to promote malignant expansion despite treatment. To better understand these interactions, we developed a real-time cell cycle-tracking mouse model of AML (Fucci-MA9) with an aim of unraveling why quiescent leukemia cells are more resistant to chemotherapy than cycling cells and proliferate during disease relapse. We found that quiescent leukemia cells were more prone to escape chemotherapy than cycling cells, leading to relapse and proliferation. Importantly, post-chemotherapy resting leukemia cells tended to localize closer to blood vessels. Mechanistically, after chemotherapy, resting leukemia cells interacted with ECs, promoting their adhesion and anti-apoptotic capacity. Further, expression analysis of ECs and leukemia cells during AML, after chemotherapy, and after relapse revealed the potential of suppressing the post-chemotherapy inflammatory response to regulate the functions of leukemia cells and ECs. These findings highlight the role of leukemia cells in evading chemotherapy by seeking refuge near blood vessels and provide important insights and directions for future AML research and treatment.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/97/e9/bs9-5-092.PMC10205361.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9518328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-01DOI: 10.1097/BS9.0000000000000144
Ru Li, Tingyu Wang, Rui Lyv, Yi Wang, Ying Yu, Yuting Yan, Qi Sun, Wenjie Xiong, Wei Liu, Weiwei Sui, Wenyang Huang, Huijun Wang, Chengwen Li, Jun Wang, Dehui Zou, Gang An, Jianxiang Wang, Lugui Qiu, Shuhua Yi
Rituximab maintenance (RM) prolongs the progression-free survival (PFS) of responding patients with follicular lymphoma (FL), but the maintenance efficacy in different Follicular Lymphoma International Prognostic Index (FLIPI) risk group is still confusing. We performed a retrospective analysis of the effect of RM treatments in patients with FL responding to induction therapy based on their FLIPI risk assessment carried out prior to treatment. We identified 93 patients between 2013 and 2019 who received RM every 3 months for ≥4 doses (RM group), and 60 patients who did not accept RM or received rituximab less than 4 doses (control group). After a median follow-up of 39 months, neither median overall survival (OS) nor PFS was reached for the entire population. The PFS was significantly prolonged in the RM group compared to the control group (median PFS NA vs 83.1 months, P = .00027). When the population was divided into the 3 FLIPI risk groups, the PFS differed significantly (4-year PFS rates, 97.5% vs 88.8% vs 72.3%, P = .01) according to group. There was no significant difference in PFS for FLIPI low-risk patients with RM compared to the control group (4-year PFS rates, 100% vs 93.8%, P = .23). However, the PFS of the RM group was significantly prolonged for FLIPI intermediate-risk (4-year PFS rates, 100% vs 70.3%, P = .00077) and high-risk patients (4-year PFS rates, 86.7% vs 57.1%, P = .023). These data suggest that standard RM significantly prolongs the PFS of patients assigned to intermediate- and high-risk FLIPI groups but not to low-risk FLIPI group, and pending larger-scale studies to validate.
利妥昔单抗维持治疗(RM)可延长滤泡性淋巴瘤(FL)患者的无进展生存期(PFS),但不同滤泡性淋巴瘤国际预后指数(FLIPI)风险组的维持疗效尚不明确。我们基于治疗前对FL患者进行的FLIPI风险评估,对RM治疗对诱导治疗的疗效进行了回顾性分析。我们在2013年至2019年期间确定了93例每3个月接受RM≥4次剂量的患者(RM组),以及60例未接受RM或接受利妥昔单抗少于4次剂量的患者(对照组)。中位随访39个月后,整个人群的中位总生存期(OS)和PFS均未达到。与对照组相比,RM组的PFS显著延长(中位PFS NA vs 83.1个月,P = 0.00027)。将人群分为3个FLIPI风险组时,各组PFS差异显著(4年PFS率,97.5% vs 88.8% vs 72.3%, P = 0.01)。与对照组相比,FLIPI低危RM患者的PFS无显著差异(4年PFS率,100% vs 93.8%, P = 0.23)。然而,RM组的FLIPI中危患者(4年PFS率,100% vs 70.3%, P = 0.00077)和高危患者(4年PFS率,86.7% vs 57.1%, P = 0.023)的PFS明显延长。这些数据表明,标准RM可显著延长中高风险FLIPI组患者的PFS,但不能延长低风险FLIPI组患者的PFS,有待更大规模的研究来验证。
{"title":"Benefit of rituximab maintenance is associated with Follicular Lymphoma International Prognostic Index in patients with follicular lymphoma.","authors":"Ru Li, Tingyu Wang, Rui Lyv, Yi Wang, Ying Yu, Yuting Yan, Qi Sun, Wenjie Xiong, Wei Liu, Weiwei Sui, Wenyang Huang, Huijun Wang, Chengwen Li, Jun Wang, Dehui Zou, Gang An, Jianxiang Wang, Lugui Qiu, Shuhua Yi","doi":"10.1097/BS9.0000000000000144","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000144","url":null,"abstract":"<p><p>Rituximab maintenance (RM) prolongs the progression-free survival (PFS) of responding patients with follicular lymphoma (FL), but the maintenance efficacy in different Follicular Lymphoma International Prognostic Index (FLIPI) risk group is still confusing. We performed a retrospective analysis of the effect of RM treatments in patients with FL responding to induction therapy based on their FLIPI risk assessment carried out prior to treatment. We identified 93 patients between 2013 and 2019 who received RM every 3 months for ≥4 doses (RM group), and 60 patients who did not accept RM or received rituximab less than 4 doses (control group). After a median follow-up of 39 months, neither median overall survival (OS) nor PFS was reached for the entire population. The PFS was significantly prolonged in the RM group compared to the control group (median PFS NA vs 83.1 months, <i>P</i> = .00027). When the population was divided into the 3 FLIPI risk groups, the PFS differed significantly (4-year PFS rates, 97.5% vs 88.8% vs 72.3%, <i>P</i> = .01) according to group. There was no significant difference in PFS for FLIPI low-risk patients with RM compared to the control group (4-year PFS rates, 100% vs 93.8%, <i>P</i> = .23). However, the PFS of the RM group was significantly prolonged for FLIPI intermediate-risk (4-year PFS rates, 100% vs 70.3%, <i>P</i> = .00077) and high-risk patients (4-year PFS rates, 86.7% vs 57.1%, <i>P</i> = .023). These data suggest that standard RM significantly prolongs the PFS of patients assigned to intermediate- and high-risk FLIPI groups but not to low-risk FLIPI group, and pending larger-scale studies to validate.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9997475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-01DOI: 10.1097/BS9.0000000000000151
Ahmad Abou Yassine, Kira MacDougall, Roula Sasso, Youssef Shammaa, Mira Alsheikh, Mohammad Abureesh, Loai Dahabra, Mohammad Alshami, Stephen Mulrooney
Hemochromatosis, either hereditary hemochromatosis (HH) or secondary hemochromatosis, consists of the accumulation of iron in the liver, heart, and other organs. It leads to end-organ damage in a proportion of affected subjects. Although liver-related morbidity (cirrhosis and hepatocellular carcinoma [HCC]) and mortality are well established, the frequency of these complications remains controversial. The aim of this study is to examine the rate of hospitalization and the incidence of iron overload-related comorbidities in patients with hemochromatosis between the years of 2002 and 2010. We queried the Nationwide Inpatient Sample (NIS) database from the year 2002 to 2010. We included adults (age ≥18 years) and used the ICD-CM 9 code 275.0x to identify hospitalized patients with a diagnosis of hemochromatosis. Data analysis for this study was generated using SAS software version 9.4. A total of 168,614 hospitalized patients between 2002 and 2010 had a diagnosis of hemochromatosis. The majority were males (57%) with a median age of 54 years (37-68), with a predominance of white patients (63.3%) followed by black (26.8%). The rate of hospitalization among patients with hemochromatosis increased by 79% between the years 2002 and 2010 (34.5/100,000 in 2002 vs 61.4/100,000 in 2010). The main associated diagnoses were diabetes mellitus (20.2%), cardiac disease, including arrhythmias (14%) and cardiomyopathy (dilated 3.8%; peri-, endo-, myocarditis 1.3%), liver cirrhosis (8.6%), HCC (1.6%), and acute liver failure (0.81%). Of note, HCC was associated with cirrhosis in 1188 patients (43% of HCC patients) and male sex (87%). Diagnostic biopsies were performed in 6023 (3.6%) of those patients and liver transplant was performed in 881 (0.5%). In-hospital mortality occurred in 3638 (2.16%) patients. In this large database study, we found a rising trend in hospitalization for hemochromatosis, possibly due to the increased recognition of this entity and billing for the condition. The incidence of cirrhosis in hemochromatosis was found to be similar to other studies (8.6% vs 9%). However, the rate of HCC was lower than previous reports (1.6% vs 2.2%-14.9%), and only 43% of HCC was associated with cirrhosis. This raises important pathophysiologic questions regarding the impact of iron overload in HCC. There has been an increase in the rate of hospitalization for patients with a diagnosis of hemochromatosis. This may be related to an increased recognition of hemochromatosis as the underlying etiology for conditions such as diabetes, cardiomyopathy, cirrhosis, and HCC. Further prospective studies are needed to clarify the burden of liver disease in HH and secondary iron overload.
血色素沉着症,无论是遗传性血色素沉着症(HH)还是继发性血色素沉着症,都是由铁在肝脏、心脏和其他器官中的积累引起的。在一部分受影响的受试者中,它会导致终末器官损伤。虽然肝脏相关的发病率(肝硬化和肝细胞癌[HCC])和死亡率已经确定,但这些并发症的频率仍然存在争议。本研究的目的是检查2002年至2010年间血色素沉着症患者的住院率和铁负荷相关合并症的发生率。我们查询了2002年至2010年全国住院病人样本(NIS)数据库。我们纳入成人(年龄≥18岁),并使用ICD-CM 9代码275.0x识别诊断为血色素沉着症的住院患者。本研究的数据分析使用SAS软件9.4版本。2002年至2010年间,共有168,614名住院患者被诊断为血色素沉着症。多数为男性(57%),中位年龄为54岁(37-68岁),白人患者居多(63.3%),其次为黑人(26.8%)。2002年至2010年间,血色素沉着症患者的住院率增加了79%(2002年为34.5/10万,2010年为61.4/10万)。主要相关诊断为糖尿病(20.2%)、心脏病(包括心律失常)(14%)和心肌病(扩张型3.8%;心肌炎、心肌炎、心肌炎1.3%)、肝硬化(8.6%)、HCC(1.6%)和急性肝衰竭(0.81%)。值得注意的是,在1188例HCC患者(43%)和男性(87%)中,HCC与肝硬化相关。其中6023例(3.6%)接受了诊断性活检,881例(0.5%)接受了肝移植。住院死亡3638例(2.16%)。在这项大型数据库研究中,我们发现血色素沉着症住院率呈上升趋势,这可能是由于对该疾病的认识和治疗费用的增加。血色素沉着症患者肝硬化的发生率与其他研究相似(8.6% vs 9%)。然而,HCC的发生率低于之前的报道(1.6% vs 2.2%-14.9%),并且只有43%的HCC与肝硬化相关。这就提出了关于铁超载在HCC中的影响的重要病理生理学问题。诊断为血色素沉着症的病人的住院率有所增加。这可能与人们越来越认识到血色素沉着症是糖尿病、心肌病、肝硬化和HCC等疾病的潜在病因有关。需要进一步的前瞻性研究来阐明HH和继发性铁超载对肝脏疾病的影响。
{"title":"The Evolution of Iron-Related Comorbidities and Hospitalization in Patients with Hemochromatosis: An Analysis of the Nationwide Inpatient Sample.","authors":"Ahmad Abou Yassine, Kira MacDougall, Roula Sasso, Youssef Shammaa, Mira Alsheikh, Mohammad Abureesh, Loai Dahabra, Mohammad Alshami, Stephen Mulrooney","doi":"10.1097/BS9.0000000000000151","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000151","url":null,"abstract":"<p><p>Hemochromatosis, either hereditary hemochromatosis (HH) or secondary hemochromatosis, consists of the accumulation of iron in the liver, heart, and other organs. It leads to end-organ damage in a proportion of affected subjects. Although liver-related morbidity (cirrhosis and hepatocellular carcinoma [HCC]) and mortality are well established, the frequency of these complications remains controversial. The aim of this study is to examine the rate of hospitalization and the incidence of iron overload-related comorbidities in patients with hemochromatosis between the years of 2002 and 2010. We queried the Nationwide Inpatient Sample (NIS) database from the year 2002 to 2010. We included adults (age ≥18 years) and used the ICD-CM 9 code 275.0x to identify hospitalized patients with a diagnosis of hemochromatosis. Data analysis for this study was generated using SAS software version 9.4. A total of 168,614 hospitalized patients between 2002 and 2010 had a diagnosis of hemochromatosis. The majority were males (57%) with a median age of 54 years (37-68), with a predominance of white patients (63.3%) followed by black (26.8%). The rate of hospitalization among patients with hemochromatosis increased by 79% between the years 2002 and 2010 (34.5/100,000 in 2002 vs 61.4/100,000 in 2010). The main associated diagnoses were diabetes mellitus (20.2%), cardiac disease, including arrhythmias (14%) and cardiomyopathy (dilated 3.8%; peri-, endo-, myocarditis 1.3%), liver cirrhosis (8.6%), HCC (1.6%), and acute liver failure (0.81%). Of note, HCC was associated with cirrhosis in 1188 patients (43% of HCC patients) and male sex (87%). Diagnostic biopsies were performed in 6023 (3.6%) of those patients and liver transplant was performed in 881 (0.5%). In-hospital mortality occurred in 3638 (2.16%) patients. In this large database study, we found a rising trend in hospitalization for hemochromatosis, possibly due to the increased recognition of this entity and billing for the condition. The incidence of cirrhosis in hemochromatosis was found to be similar to other studies (8.6% vs 9%). However, the rate of HCC was lower than previous reports (1.6% vs 2.2%-14.9%), and only 43% of HCC was associated with cirrhosis. This raises important pathophysiologic questions regarding the impact of iron overload in HCC. There has been an increase in the rate of hospitalization for patients with a diagnosis of hemochromatosis. This may be related to an increased recognition of hemochromatosis as the underlying etiology for conditions such as diabetes, cardiomyopathy, cirrhosis, and HCC. Further prospective studies are needed to clarify the burden of liver disease in HH and secondary iron overload.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9530767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}