Hematology最新文献

To investigate the role of ALKBH3 in acute myeloid leukemia (AML), we constructed an animal model of xenotransplantation of AML. Our study demonstrated that ALKBH3-mediated m1A demethylation inhibits ferroptosis in KG-1 cells by increasing ATF4 expression, thus promoting the development of AML. These findings suggest that reducing ALKBH3 expression may be a potential strategy to mitigate AML progression.

Background: Acute myeloid leukemia (AML) is characterized by the unrestrained proliferation of myeloid cells. Studies have shown that ALKBH3 is upregulated in most tumors, but the role of ALKBH3 in AML remains unclear.Methods: In this study, we investigated the function of ALKBH3 in AML cells (KG-1) by immunofluorescence, ELISA, flow cytometry, HE staining, and Western blotting.Results: Our results revealed that ALKBH3 is upregulated in AML and that the downregulation of ALKBH3 inhibited KG-1 cell proliferation and promoted cell apoptosis; at the same time, ALKBH3 upregulated ATF4 expression through m1A demethylation, and the knockdown of ATF4 resulted in increased ferrous iron content; TFR1, ACSL4, and PTGS2 expression; and ROS and MDA levels, whereas SOD and GSH levels and the expression levels of ATF4, SLC7A11, GPX4, and FTH1 decreased in KG-1 cells, thereby promoting ferroptosis. Mechanistically, ALKBH3-mediated m1A demethylation suppressed ferroptosis in KG-1 cells by increasing ATF4 expression, thereby promoting the development of AML.Conclusions: Our study indicated that reducing the expression of ALKBH3 might be a potential target for improving AML symptoms.

Introduction: Cases of warm autoimmune hemolytic anemia (wAIHA) often present with life-threatening levels of hemoglobin requiring red blood cell (RBC) transfusion support.

Aim: This literature review assessed the occurrence, safety, effectiveness, and hospitalization burden of RBC transfusions in the management of patients with wAIHA.

Methods: Electronic databases (Embase, MEDLINE) were searched from inception to December 2021 along with additional searches conducted up to March 2024.

Results: Of the 1478 articles screened, 17 observational studies and reviews were included. These studies demonstrated the use of 1-50 red blood cell transfusions to reach clinically acceptable hemoglobin levels in patients with wAIHA. In general, pre-transfusion hemoglobin levels were 6 g/dL and increased by an average 1.2 g/dL following a transfusion. Approximately 50% of patients with primary or secondary wAIHA suffered relapses. No data was available to distinguish between RBC transfusions used at initial presentation versus during relapse. Five studies found no increase in hemolysis or serious adverse reactions following transfusions and two studies reported mild transfusion-related adverse effects. Limited data was available regarding the hospitalization burden of RBC transfusion. Patients with wAIHA requiring transfusions had a median hospital stay from 15 to 17 days, which is considerably higher than all causes hospitalization of 4.5 days for 2023 U.S.

Conclusion: In patients with wAIHA, data supports wide variability in occurrence, but relative safety and effectiveness of RBC transfusions as supportive therapy. Additional studies are needed to assess the occurrence, safety, and hospitalization burden of RBC transfusions relative to other therapies in chronic relapsing wAIHA.

Background: Dehydrated Hereditary Stomatocytosis (DHS), also known as Hereditary Xerocytosis (HX), is a rare genetic disorder primarily arising from gain-of-function mutations in PIEZO1, which disrupt mechanosensitive ion channels on red blood cell membranes. This dysfunction leads to cellular dehydration and chronic anemia, while DHS/HX cells exhibit increased hypotonic resistance. Interpreting PIEZO1 variants requires integrating clinical findings with specialized knowledge.

Methods: Laboratory tests, whole-genome sequencing, and Sanger sequencing were conducted for clinical phenotyping and identification of disease-causing mutations within the proband and his parents.

Results: The proband was found to have both β-thalassemia trait and Dehydrated Hereditary Stomatocytosis. The proband inherited compound heterozygous mutations in the PIEZO1 gene (c.136G > A and c.6307C > G) from his mother and father, respectively. Additionally, the proband had a heterozygous β-globin gene mutation (c.315 + 2delT) inherited from his father.

Conclusion: Compared to patients with either DHS/HX or β-thalassemia alone, this patient, as a β-thalassemia carrier with suspected Dehydrated Hereditary Stomatocytosis, exhibited highly complex laboratory findings. Genetic testing played a crucial role in diagnosing conditions with overlapping clinical features. Given the increased risk of thromboembolic complications, splenectomy is contraindicated in DHS/HX patients, highlighting the necessity for precise diagnosis of DHS/HX and molecular confirmation of suspected hereditary red blood cell disorders.

Background: The effect of methotrexate (MTX)-related toxicity on childhood acute lymphoblastic leukemia (ALL) is controversial. Hence, this meta-analysis aimed to investigate the association between ABCB1 C3435 T polymorphism- and methotrexate-related toxicity in pediatric acute lymphoblastic leukemia.

Methods: Relevant studies were systematically searched and extracted from multiple databases including PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases up to 1 June, 2024.

Results: A total of 13 articles met the criteria, including 1506 patients. The results showed that ABCB1 C3435 T polymorphism was significantly associated with MTX-induced hepatotoxicity (CT/TT vs. CC: OR: 2.15, 95% CI: 1.40-3.32). There was no significant difference between ABCB1 C3435 T polymorphism and mucositis, myelosuppression, nephrotoxicity, gastrointestinal toxicity in pediatric ALL treated with MTX.

Conclusions: Our meta-analysis suggests that the ABCB1 C3435 T mutation may enhance the MTX-induced hepatotoxicity in childhood acute lymphoblastic leukemia.

Background: The present study systematically explores the correlation between the Prognostic Nutritional Index (PNI) and anemia, and further analysis of its association with all-cause mortality among populations affected by anemia.

Methods: Data were taken from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. We utilized multiple logistic regression models, Cox proportional hazards models, restricted cubic spline (RCS) analysis, and time-dependent receiver operating characteristic (ROC) analysis. As for the verification of the result robustness, subgroup and sensitivity analyses were implemented.

Results: A cohort of 28,511 participants was examined, of whom 2647 (9.28%) had anemia. An inverse relationship of PNI with anemia was detected in the fully adjusted model (OR = 0.82, 95%CI: 0.80-0.84). Cox regression showed that lower PNI levels were linked to higher all-cause mortality in people with anemia (HR = 0.91, 95%CI: 0.88-0.95). A non-linear correlation between PNI and mortality was detected through RCS analysis (P < 0.001). Significant interaction effects of PNI with mortality were observed across diabetes and BMI subgroups (P < 0.05). The predictive power of PNI for all-cause mortality among anemia individuals showed areas under the curve (AUC) values of 0.702, 0.806, and 0.813 for 3-, 5-, and 10-year predictions, respectively.

Conclusion: PNI demonstrates a negative association with anemia and a similar negative relationship with all-cause mortality in individuals with anemia. Future studies are warranted to substantiate these findings.

Background: Although a substantial body of research has underscored the pivotal role of inflammatory proteins in hematologic malignancies, precise understanding of the underlying mechanisms is limited. Therefore, it's necessary to explore the possible causal relationships between specific circulating inflammatory proteins and these malignancies by using a genome-wide association approach.

Methods: To evaluate the possible causal effects, we performed a two-sample Mendelian randomization (MR) study. Summary statistics for 91 proteins, sourced from large-scale genome-wide association studies, were integrated with data on 11 hematologic malignancies from the FinnGen consortium. Inverse variance weighting was applied as the primary method for MR analysis, with detailed sensitivity analyses conducted to ensure robustness. Furthermore, protein-protein interaction analysis and cross-cancer effect assessments were performed to identify potential common drug targets.

Results: Our analysis demonstrated both positive and negative associations of circulating inflammatory proteins on the development of 11 hematologic malignancies. Nine proteins exhibited cross-cancer effects. MCP-1, CXCL8, IL-1α, and SCF were associated with an increased risk of hematologic malignancies, while IFN-γ, IL-10, CD40, SULT1A1, and CXCL5 were associated with a reduced risk.

Conclusions: The results of the study provided possible causal evidence for the involvement of circulating inflammatory proteins in the pathogenesis of eleven hematologic malignancies. Nine proteins with cross-cancer effects were of special interest, and their potential as targets in the therapeutic intervention of blood malignancies was highlighted.

Objectives: To establish a novel Inflammation Prognostic Score Index (IPSI) and evaluate its prognostic value and complementary role to the International Staging System (ISS) in newly diagnosed multiple myeloma (MM).

Methods: This retrospective study analyzed 98 newly diagnosed MM patients. ROC-derived cutoffs stratified patients by RDW, PLT, NMLR, SII, and SIRI. The IPSI was constructed by assigning 1 point each to elevated RDW, low PLT, and high NMLR, defining three risk groups: 0-1, 2, and 3 risk factor groups. Survival and ISS correlations were evaluated using Kaplan-Meier, Cox, and Spearman's tests.

Results: Multivariate analysis confirmed RDW, PLT, and NMLR as independent predictors of overall survival (OS) (all P < 0.05). Based on these, IPSI stratified patients into three risk groups: 0-1, 2, and 3 risk factor groups, with median OS of 24, 21.5, and 14 months, respectively (log-rank P < 0.001). IPSI was an independent prognostic factor (2-risk-factors group: HR = 8.74; 3-risk-factors group: HR = 18.98 vs 0-1-risk-factors group; both P < 0.001) and correlated with ISS stage (r_s = 0.35, P < 0.001). Critically, IPSI refined risk stratification within all ISS subgroups (P < 0.001). SII and SIRI correlated with ISS but were not independent prognostic factors.

Conclusions: As an independent prognostic index that integrates RDW, PLT, and NMLR, IPSI optimizes ISS staging and provides a cost-effective risk stratification tool. It may be a good measure indice of identifying high-risk MM patients in resource constraint setting where access to molecular testing is not available.

Objectives: HLA Class I, HPA (Human platelet antigen), CD36 allo/isoantibodies, and platelet glycoprotein autoantibodies are the primary causes of immune-mediated platelet transfusion refractoriness (iPTR). Detecting these antibodies and selecting antigen-negative platelets for transfusion effectively manages iPTR, but large-scale data on platelet antibody distribution in the Chinese population are scarce.

Methods: From Jan 2021 to Dec 2023, 2073 patients with suspected iPTR underwent platelet cross-matching via solid-phase red blood cell adherence. Sera from those with positive cross-matching (≥1 donor) were analyzed for platelet antibodies using Luminex. Correlations between antibody prevalence, age, gender, and diseases were statistically analyzed.

Results: 621 patients, 30.0% (621/2073) had positive cross-matching with ≥1 donor. Furthermore, 374 (60.2%) patients had platelet antibodies. Moreover, 429 antibodies were detected in these patients, and the constituent ratios of HLA Class I alloantibodies, HPA alloantibodies, autoantibodies (GPIIb/IIIa, etc), and CD36 isoantibodies were 78.09%, 4.65%, 17.01%, and 0.23%, respectively. Abs ranked as follows: HLA Class I > GPIIb/IIIa > GPIa/IIa > HPA-5b, GPIb/IX > HPA-3a > HPA-1b, 2b > HPA-3b, 4b, CD36. Lastly, positive platelet antibodies prevalence correlated with age and sex in leukemia and solid tumor patient groups.

Discussion: This study clarified platelet antibody distribution in Chinese iPTR patients. Besides HLA Class I antibodies, autoantibodies against platelet glycoproteins play a key role. Among HPA antibodies, HPA-5b may predominate in the Chinese population instead of HPA-1a.

The present study aimed to compare the efficacy and safety of hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) for hepatitis-associated aplastic anemia (HAAA). Studies comparing HSCT with IST in HAAA were retrieved from inception to July 22, 2024, including 12 studies with a total of 544 cases for meta-analysis. Meta-analysis demonstrated significantly superior outcomes in the HSCT group versus IST, which was manifested as lower overall mortality (P < 0.01), higher overall response rate (P < 0.001), and improved five-year overall survival (P < 0.05), yielding a pooled RR of 1.67 (95% CI: 1.15-2.44), 0.75 (95% CI: 0.66-0.86) and 0.88 (95% CI: 0.78-0.99), respectively. However, no benefit was observed in one-year survival (P = 0.08). Further subgroup analysis indicated that the advantage of mortality (P < 0.05, RR = 1.67, 95% CI: 1.10-2.55) and five-year overall survival (P = 0.05, RR = 0.84, 95% CI: 0.71-1.00) only achieved in patients under 20 years old. There was no significant difference in the overall response and one-year overall survival for each age group. Additionally, for the IST selection, a combination of cyclosporine (CSA) and antithymocyte globulin/antilymphocyte globulin (ATG/ALG) was preferred over the CSA-only regimen (effectiveness of 78.57% vs. 50.00%), although the difference was not statistically significant (P = 0.10, RR = 1.56, 95% CI: 0.92-2.66). This study showed that HSCT had a higher effective rate, greater long-term survival and lower mortality compared to IST, especially for patients under 20 years old, who should receive HSCT treatment as possible.

Background: Luspatercept, approved by the FDA and EMA for patients with transfusion-dependent lower-risk myelodysplastic syndrome (LR-MDS) unresponsive to erythropoiesis-stimulating agents (ESAs), lacks extensive real-world data, particularly in China.

Methods: We retrospectively analyzed 14 LR-MDS-SF3B1 patients treated with luspatercept for ≥12 weeks.

Results: Median age was 60 years (range 47-72); 42.9% were male. Before treatment, 78.6% were transfusion-dependent, and 42.9% had prior ESA therapy. At median 24-week follow-up (range 12-44), erythroid response rates were 71.43% (week 12), 75.00% (week 16), and 62.50% (week 24). Hemoglobin levels significantly improved at weeks 12 and 24 (P = 0.013, P = 0.005). No grade 3-4 adverse events occurred. Hematologic improvement-erythroid (HI-E) patients exhibited higher white blood cells, neutrophils, and reticulocytes at week 12 versus non-HI-E patients. Bone marrow analysis revealed erythroid hyperplasia in HI-E patients, with higher erythrocyte percentage (56.00% vs. 34.00%, P = 0.023), lower myeloid-to-erythroid ratio (0.60 vs. 1.59, P = 0.024), and increased polychromatic erythroblasts (19.50% vs. 10.00%, P = 0.034).

Conclusions: Luspatercept demonstrated efficacy and safety in Chinese LR-MDSSF3B1 patients. Greater erythroid hyperplasia correlated with better clinical response.