Hematology最新文献

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.

Objective: Examine Bach1 protein expression in bone marrow biopsy specimens obtained from newly diagnosed multiple myeloma (NDMM) and iron deficiency anemia (IDA) patients. Conduct a thorough analysis to explore the potential connection between Bach1 and the onset as well as treatment response of NDMM.

Methods: This study investigated Bach1 expression in bone marrow biopsy tissues from NDMM and IDA patients. Immunohistochemical staining and Image-pro Plus software were utilized for quantitatively obtaining the expression level of Bach1 protein. Arrange Bach1 expression levels from high to low, and use its median expression level as the threshold. Samples with Bach1 expression level above the median are categorized as the high-expression group, while those below the median are categorized as the low-expression group. Under this grouping, a detailed discussion was conducted to explore relationship of the Bach1 expression level with the patients' gender, ISS stage, and survival rate based on the Bortezomib (Btz) therapy.

Results: Our experiment indicates that the expression level of Bach1 in NDMM patients is significantly higher than in IDA patients. Furthermore, we discovered that patients in the high-expression group exhibit better prognosis compared to those in the low-expression group after Btz-treatment. Bioinformatics analysis further confirms this conclusion.

Conclusion: By categorizing Bach1 expression level as high and low, our study offers a unique perspective on understanding the relationship between Bach1 and NDMM.

Background: Several non-invasive technologies are nowadays available in the market which claim to determine the hemoglobin levels instantly without the requirement of the blood sample. But no study has shown the significance of such non-invasive devices on a routine basis for determining their impact on anemia reduction programs. This study is conducted to determine the impact of regular hemoglobin screening on the women population to determine its potential in reducing anemia, using a digitalized non-invasive device.

Method: A cross-sectional study was conducted on 203 women of reproductive age group, residing in the Moradabad district. Repetitive readings were taken after a time interval of a minimum of 1 month for determining the impact of regular screening. The entire data collection process was carried out using the EzeCheck mobile app.

Results: It was observed that the prevalence of anemia was reduced upon the second time screening and was accepted by the women population. Repetitive testing has a significant impact on reducing anemia prevalence. Also, the simplified non-invasive technology for estimating the hemoglobin values, makes the user more comfortable to take the test.

Conclusion: Non-invasive devices should be used regularly to keep track of hemoglobin levels which will help in the effective treatment of anemia. The mobile app-based testing could help to easily evaluate the reports of the patients from any remote location with instant result interpretation and health assistance.

Background: Hemolytic disease of the newborn (HDN) is a common condition that can have a severe impact on the health of newborns due to the hemolytic reactions it triggers. Although numerous studies have focused on understanding the pathogenesis of HDN, there are still many unanswered questions.

Methods: In this retrospective study, serum samples were collected from 15 healthy newborns and 8 infants diagnosed with hemolytic disease. The relationship between different metabolites and various IgG subtypes in Healthy, HDN and BLI groups was studied by biochemical technique and enzyme-linked immunosorbent assay (ELISA). Metabolomics analysis was conducted to identify the differential metabolites associated with HDN. Subsequently, Pearson's correlation analysis was used to determine the relation of these differential metabolites with IgG isoforms. The relationship between the metabolites and IgG subtypes was observed after treatment.

Results: The study results revealed that infants with hemolytic disease exhibited abnormal elevations in TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4 levels when compared to healthy newborns. Additionally, differences in metabolite contents were also observed. N, N-DIMETHYLARGININE showed negative correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4, while 2-HYDROXYBUTYRATE, AMINOISOBUTANOATE, Inosine, and ALLYL ISOTHIOCYANATE exhibited positive correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4. Through metabolomics-based research, we have discovered associations between differential metabolites and different IgG isoforms during the onset of HDN.

Conclusion: These findings suggest that changes in metabolite and IgG isoform levels are linked to HDN. Understanding the involvement of IgG isoforms and metabolites can provide valuable guidance for the diagnosis and treatment of HDN.

Background: Acute myeloid leukemia (AML) with t(8;21) manifests as a diverse hematological malignancy. Although it was categorized into a favorable subtype, 30-40% of patients experience relapse. The objective of this research was to devise a nomogram for the accurate anticipation of both overall survival (OS) and cancer-specific survival (CSS) in t(8;21) AML.

Methods: From the Surveillance, Epidemiology, and End Results (SEER) database, individuals diagnosed with t(8;21) AML from 2000 to 2018 were selected. Prognostic factors for t(8;21) AML were identified using Cox regression analysis and Akaike Information Criterion (AIC), forming the basis for constructing prognostic nomograms.

Results: Key variables, including first primary tumor, age group, race, and chemotherapy, were identified and integrated into the nomogram. The C-index values for the nomograms predicting OS and CSS were 0.753 (validation: 0.765) and 0.764 (validation: 0.757), respectively. Ultimately, based on nomogram scores, patients were stratified into high-risk and low-risk groups, revealing significant disparities in both OS and CSS between these groups (P < 0.001).

Conclusion: This study innovatively crafted nomograms, incorporating clinical and therapeutic variables, to forecast the 1-, 3-, and 5-year survival rates for individuals with t(8;21) AML.

Background: Observational studies have found a link between lipid metabolism disorders and aplastic anemia (AA). However, due to confounding variables and reverse causation, it is difficult to conclude such a causal link. The precise mechanism and potential implications of lipid metabolism disorder in AA remain unclear, necessitating further studies in this area.

Method: This study aimed to examine the causal relationship between 38 different subtypes of triacylglycerols and AA using two-sample Mendelian randomization (MR). Additionally, two-step MR analyses were conducted to investigate the mediating effects of vitamin A to oleoyl-linoleoyl-glycerol (18:1-18:2) ratio.

Results: MR analysis showed that triacylglycerol (53:3) levels were positively associated with the risk of AA [inverse variance weighting (IVW): odds ratio (OR) = 1.131,95% confidence interval (CI):1.029-1.243, P = 0.011; Bayesian weighted MR (BWMR): OR = 1.137,95% CI:1.031-1.254, P = 0.010]. Triacylglycerol (53:3) level showed no inverse causality with AA (IVW:P = 0.834; BWMR:P = 0.349). Mediation analyses showed that increasing the vitamin A to oleoyl-linoleoyl-glycerol (18:1-18:2) ratio can decrease the risk of AA.

Conclusion: This study revealed the association between vitamin A to oleoyl-linoleoyl-glycerol (18:1-18:2) ratio, triacylglycerol (53:3) levels and AA, and indicated that lowering triacylglycerol (53:3) levels can reduce the risk of AA.

ABSTRACTImmune thrombocytopenia (ITP), an autoimmune disease characterized by low platelet counts and increased bleeding risk, can impair health-related quality of life (HRQoL), impacting patients' daily lives and mental health. A number of patient-reported outcome (PRO) measures (both generic and specific to ITP) can be used to understand the impact of ITP on HRQoL and generate evidence to guide disease management. As well-developed PRO tools could help in HRQoL assessment, their optimization could help to solidify a patient-centric approach to ITP management. Shared decision-making is a collaborative process between a patient and their healthcare professional in making decisions about care. Treatment decisions based on this shared process between physician and patient are recommended by clinical guidelines. The goal of this narrative review is to discuss treatment decisions with regards to patient-centric ITP management, with a focus on the impact of PRO measures and the process of shared decision-making in practice.

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.

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.

Background: Hemoglobin (Hb), a red pigment of red blood cells (RBCs), carries oxygen from the lungs to different organs of the body and transports carbon dioxide back to the lungs. Any fault present in the Hb structure leads to undesirable functional effects of the RBCs, such as sickle cell anemia (SCA), thalassemia, etc. Hemoglobinopathies affect around 7% of people in both developed and developing countries globally. The aim of the present study was to determine the prevalence and carrier frequencies of hemoglobinopathies including SCA, thalassemia, and other abnormal Hb variants among Malayali tribes in the Jawadhu hills of Tiruvannamalai district, Tamil Nadu, India.

Methods: A community-based cross-sectional study was carried out among 443 Malayali tribes inhabiting the Jawadhu hills of Tiruvannamalai district from July 2022 to September 2022. The RBC indices were analyzed using an automated 5-part hematology analyzer (Mindray, BC-5150) and hemoglobin fractions were done using the HPLC system (Bio-Rad, D-10) following standard protocols.

Findings: A total of 443 participants were screened, out of whom 14.67% had an abnormal Hb fraction, 83.30% were identified as normal, and 2.03% were borderline. Notably, the study revealed a prevalence of 0.68% for the α-thalassemia trait and 13.99% for the β-thalassemia trait.

Interpretation: Haemoglobinopathies, specifically the β-thalassemia trait, were most prevalent among the Malayali tribal population of Tamil Nadu residing in the Jawadhu hills of Tiruvannamalai district. Hence, we need special attention for creating awareness, increasing hemoglobinopathies screening programs, and improving the importance of tribal health conditions by the government and non-governmental organizations (NGOs) for the betterment of the ethnic tribes.