Leukemia research最新文献

{"title":"Clinicopathologic, genetic, and prognostic characteristics of single-hit versus multi-hit TP53-mutated chronic lymphocytic leukemia in the era of novel therapies","authors":"Hamza Tariq ,&nbsp;Brian Vadasz ,&nbsp;Juehua Gao,&nbsp;Yi-Hua Chen,&nbsp;Qing Ching Chen,&nbsp;Madina Sukhanova","doi":"10.1016/j.leukres.2025.107911","DOIUrl":"10.1016/j.leukres.2025.107911","url":null,"abstract":"<div><h3>Background</h3><div><em>TP53</em> alteration is the most important adverse prognostic genetic indicator in chronic lymphocytic leukemia (CLL); however, the significance of the allele status of <em>TP53</em>, i.e., single hit (SH) vs. multi hit (MH) state, is not well characterized, particularly in the context of biological targeted therapies.</div></div><div><h3>Methods</h3><div>We retrospectively studied patients diagnosed with <em>TP53</em>-mutated CLL and treated with targeted therapies at our institution between 01/2019 and 05/2024. Clinical, genetic, and survival data were compared between SH and MH <em>TP53</em>-mutated CLL groups.</div></div><div><h3>Results</h3><div>A total of 58 cases were identified, including 13 (22.5 %) with SH and 45 (77.5 %) with MH <em>TP53</em> mutations. MH <em>TP53</em>-mutated CLLs showed significantly greater anemia, neutropenia, and thrombocytopenia, more frequent complex karyotypes (82.3 % vs. 25 %; p = 0.0001), and a higher number of co-mutated genes (median: 1.68 vs. 1.23 mutations/case; p = 0.03) compared to SH cases. However, the severity of clinical symptoms, frequency of splenomegaly, serum LDH, Rai staging, need for therapeutic intervention, time to first treatment, need for &gt; 1 line of therapy, time to second treatment, incidence of Richter transformation, and overall survival (2 and 5-year survival rates for MH vs. SH: 69 % vs.75 % and 52 % vs.75 %, respectively; p = 0.48) did not differ significantly between SH and MH <em>TP53</em>-mutated CLLs.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that SH <em>TP53</em>-mutated CLLs share several of the adverse clinicopathologic attributes of their MH counterparts. Recognizing SH <em>TP53</em>-mutated CLL as a high-risk genetic subgroup is essential to ensure precise prognostication and optimal therapy for these patients.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"156 ","pages":"Article 107911"},"PeriodicalIF":2.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596597","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}

{"title":"Advancements in Autoimmune Hemolytic Anemia (AIHA) treatment: Exploring emerging therapies","authors":"Debanjan Mukherjee ,&nbsp;Prabhjot Kaur ,&nbsp;Amandeep Singh ,&nbsp;Manish Kumar ,&nbsp;Sheeba Shafi ,&nbsp;Prabhat Kumar Upadhyay ,&nbsp;Abhishek Tiwari ,&nbsp;Varsha Tiwari ,&nbsp;Naresh Kumar Rangra ,&nbsp;Vidhya Thirunavukkarasu ,&nbsp;Sheeba Kumari ,&nbsp;Nidhi Arora ,&nbsp;Yukta Garg ,&nbsp;Nandini Sharma","doi":"10.1016/j.leukres.2025.107910","DOIUrl":"10.1016/j.leukres.2025.107910","url":null,"abstract":"<div><div>In a rare condition known as AIHA (Autoimmune Hemolytic Anemia), red blood cells are destroyed by the immune system. This type of anemia is it. More creative therapeutic options have emerged as a result of AIHA therapy outcomes, and these are thought to significantly improve the patient's condition. This summary sheds light on novel therapies that target specific pathways. B-cell-directed therapies, phagocytosis inhibitors, complement inhibitors, and FcRn inhibitors are examples of patient-specific, pathway-oriented treatments. These innovative treatments, which are yet to be implemented in clinical settings, have the potential to enhance the management of AIHA and can be used in conjunction with other treatments that have fewer side effects than conventional therapies. In addition to their potential, methods in this emerging field also make clinical adoption challenging. Striking a balance between delivering cutting-edge care and protecting physicians' income is difficult due to the high costs. Because they maximize treatment outcomes and enable treatments to be precisely tailored to each patient's unique needs, individualized medicine and combined therapies are extremely advantageous. To fully realize the potential of AIHA therapies and transform the way AIHA is managed, a number of obstacles must be removed and these treatments made easily accessible to all.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"156 ","pages":"Article 107910"},"PeriodicalIF":2.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144623448","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}

{"title":"Exploring the pathogenesis of extranodal natural killer/T cell lymphoma complicated With EBV via microarray data analysis","authors":"Yin-yin Peng,&nbsp;Xiao-qiong Tang,&nbsp;Xin Wang","doi":"10.1016/j.leukres.2025.107909","DOIUrl":"10.1016/j.leukres.2025.107909","url":null,"abstract":"<div><h3>Objectives</h3><div>To identify the common genes playing roles in the development of both the Extranodal Natural Killer/T-cell lymphoma (ENKL) and Epstein-Barr virus (EBV), and to analyze their enrichment, protein-protein interaction (PPI) nework, and their hub genes.</div></div><div><h3>Methods</h3><div>We analyzed the differential expressed genes (DEGs) of data sets GSE85599 and GSE169644 from the Gene Expression Omnibus (GEO) database using its GEO2R tool, analyzed the PPI network of DEGs using STRING database, analyzed the hub genes using Cytoscape software, and analyzed the enrichment of DEGs using DAVID database.</div></div><div><h3>Results</h3><div>We identified 152 DEGs, and 14 hub genes among them, including TOP2A, AURKB, CDC20, MCM4, CCNB1, TYMS, FEN1, RRM2, CCNA2, MCM3, KIF11, BUB1, MCM6 and CDC6. PPI network and enrichment analysis show that DEGs are highly relavant with the process related with nucleus.</div></div><div><h3>Conclusions</h3><div>In this study we identified the common DEGs of ENKL and EBV infections, found 14 hub DEGs that may mediate between them. Hope this study could provide new insights for further study of the molecular mechanism between EBV infection and ENKL.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"156 ","pages":"Article 107909"},"PeriodicalIF":2.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518726","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}

{"title":"HDAC inhibitors repress Tek and Angpt1 expression and proliferation in RUNX1-MECOM-type leukemia cells","authors":"Fumi Nakamura ,&nbsp;Yuka Nakamura ,&nbsp;Ko Sasaki ,&nbsp;Ieharu Yamazaki ,&nbsp;Yoichi Imai ,&nbsp;Kinuko Mitani","doi":"10.1016/j.leukres.2025.107738","DOIUrl":"10.1016/j.leukres.2025.107738","url":null,"abstract":"<div><div>The <em>RUNX1-MECOM</em> fusion gene generated by the t(3;21)(q26;q22) translocation is a causative gene of acute megakaryoblastic leukemia, and the generated product performs various molecular functions by recruiting histone deacetylase (HDAC). We had previously established a mouse bone marrow transplantation model through the retroviral transduction of <em>RUNX1-MECOM</em>. This model demonstrated that <em>RUNX1-MECOM</em>-expressing cells developed acute megakaryoblastic leukemia and were serially transplantable. Gene expression analyses using quantitative RT-PCR arrays revealed that <em>Angpt1</em> (<em>Angiopoietin 1)</em> and <em>Tek</em> transcripts were elevated in the leukemic cells. In this study, we confirmed the concomitant expression of Angpt1 and Tek proteins in the <em>RUNX1-MECOM</em>-expressing cells. When the primary leukemic cells were stimulated with exogenous Angpt1, endogenous Tek was phosphorylated, followed by the phosphorylation of downstream Akt. Angpt1 and Tek may form a circuit of an autocrine loop and enhance leukemia cell survival. Interestingly, the expression of Tek and Angpt1 was downregulated by HDAC inhibitors (HDACi), trichostatin A (TSA) and valproic acid (VPA). Therefore, HDACi may block the Angpt1 and Tek autocrine loop. Both TSA and VPA inhibited the growth of <em>RUNX1-MECOM</em>-expressing cells <em>in vitro</em> by inducing cell cycle arrest and apoptosis. Electron microscopic analysis further indicated that partial megakaryocytic differentiation was induced after HDACi treatment. Furthermore, intraperitoneal injection with VPA, but not TSA, extended the survival of the secondary transplanted mice. These data demonstrate the potential of HDACi as a promising targeted treatment for <em>RUNX1-MECOM</em>-type leukemia.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"156 ","pages":"Article 107738"},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470283","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}

{"title":"Involvement of THBS1 in myeloid sarcoma of acute myeloid leukemia","authors":"Zhiyao Ren ,&nbsp;Jolien Vanhooren ,&nbsp;Barbara De Moerloose ,&nbsp;Tim Lammens","doi":"10.1016/j.leukres.2025.107737","DOIUrl":"10.1016/j.leukres.2025.107737","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"155 ","pages":"Article 107737"},"PeriodicalIF":2.1,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472371","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}

{"title":"Phase 1 first-in-human dose-expansion study of the oral SF3B1 modulator H3B‑8800 in lower-risk myelodysplastic syndrome","authors":"James M. Foran ,&nbsp;Guillermo F. Sanz ,&nbsp;Justin M. Watts ,&nbsp;Andrew M. Brunner ,&nbsp;Gaelle Fossard ,&nbsp;Matteo Giovanni Della Porta ,&nbsp;Xavier Cheng-Hong Tsai ,&nbsp;Guillermo Garcia-Manero ,&nbsp;Sophie Dimicoli-Salazar ,&nbsp;Luke Fletcher ,&nbsp;Yoo Jin Kim ,&nbsp;Patricia Font ,&nbsp;Ana Alfonso-Piérola ,&nbsp;Juan Manuel Alonso-Dominguez ,&nbsp;Christopher Benton ,&nbsp;Junshik Hong ,&nbsp;Luca Malcovati ,&nbsp;Dominiek Mazure ,&nbsp;Je-Hwan Lee ,&nbsp;Su-Peng Yeh ,&nbsp;Richard M. Stone","doi":"10.1016/j.leukres.2025.107735","DOIUrl":"10.1016/j.leukres.2025.107735","url":null,"abstract":"<div><h3>Objective</h3><div>To assess the efficacy and safety of H3B-8800 at two dose regimens in patients with transfusion-dependent lower-risk myelodysplastic neoplasms (LR-MDS) with somatic <em>SF3B1</em> mutations.</div></div><div><h3>Methods</h3><div>In this Phase 1 multicenter study, adults with LR-MDS with <em>SF3B1</em> mutations were enrolled in two expansion cohorts: 10 mg and 5 mg twice a day (BID). Patients were red blood cell (RBC) transfusion-dependent, defined as ≥ 4 RBC units in 8 weeks in cohort 1 and ≥ 3 RBC units in ≥ 2 transfusions in 16 weeks in cohort 2 (patients naïve to hypomethylating agents and lenalidomide). The primary endpoint was RBC transfusion independence (TI) ≥ 8 weeks. Adverse events (AEs) during treatment were assessed in each dose cohort.</div></div><div><h3>Results</h3><div>In cohort 1 (n = 7), the H3B-8800 starting dose was reduced to 5 mg BID in the last two patients due to thrombocytopenia; this dose was selected for cohort 2 (n = 36). The median number of 28-day cycles on therapy was 2.7 and 4.8, with dose adjustments due to AEs in five (71.4 %) and 25 (69.4 %) patients in cohorts 1 and 2, respectively. The most frequently experienced AE was diarrhea. Two (28.6 %) patients in cohort 1 and seven (19.4 %) in cohort 2 developed atrial fibrillation. Two patients in each cohort achieved one interval of RBC-TI ≥ 8 weeks.</div></div><div><h3>Conclusion</h3><div>The AE profile was similar to that reported previously, with a slightly higher incidence of atrial fibrillation. However, the low RBC-TI rate suggests insufficient efficacy of H3B-8800 at the dose levels tested. Further exploration of dosing schedules is warranted.</div></div><div><h3>Trial Registration Number and Date</h3><div>NCT02841540. 22 July 2016</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"156 ","pages":"Article 107735"},"PeriodicalIF":2.1,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596596","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}

{"title":"Clinical characteristics and prognostic significance of co-mutated SETBP1/GATA2 myeloid neoplasms","authors":"Yazan Jabban ,&nbsp;Rong He ,&nbsp;Kurt Bessonen ,&nbsp;Patricia Greipp ,&nbsp;Dragan Jevremovic ,&nbsp;James Foran ,&nbsp;Cecilia Arana Yi ,&nbsp;Antoine N. Saliba ,&nbsp;Mehrdad Hefazi Torghabeh ,&nbsp;Aasiya Matin ,&nbsp;William Hogan ,&nbsp;Abhishek Mangaonkar ,&nbsp;Mrinal Patnaik ,&nbsp;Mithun Shah ,&nbsp;Hassan Alkhateeb ,&nbsp;Aref Al-Kali","doi":"10.1016/j.leukres.2025.107734","DOIUrl":"10.1016/j.leukres.2025.107734","url":null,"abstract":"<div><div><em>SETBP1</em> gene, located on 18q12.3, is a major oncogene in myeloid neoplasms. <em>GATA2</em> gene, located on 3q21, is one of the six <em>GATA</em> transcription factors regulating gene expression via two conserved zinc finger domains (ZF). Previous data suggested that in patients with germline <em>GATA2</em> mutation (m), acquisition of a somatic <em>SETBP1</em> mutation (m) was associated with leukemic transformation among patients with AML, excess blast MDS and CMML. We hypothesize that the co-occurrence of <em>SETBP1m</em> and <em>GATA2m</em> have a unique impact on the clinical and molecular characteristics of myeloid neoplasms. After IRB approval, we retrospectively reviewed the charts of patients who had myeloid NGS panel results between 2016 and 2023. All patients with myeloid neoplasms who had either <em>SETBP1m</em> or <em>GATA2</em>m were included. One hundred sixty-eight patients had either <em>SETBP1m</em> and/or <em>GATA2m</em>; 105 patients had <em>SETBP1m</em>, 54 had <em>GATA2m</em> and 9 had both <em>SETBP1m</em> and <em>GATA2m.</em> Majority (66.1 %) were males with a median age of 71.3 years. At time of NGS, MDS/MPN was the most common diagnosis (32.1 %), followed by MDS (30 %) and AML (20.2 %). In <em>SETBP1m</em>/<em>GATA2m</em> patients, 7 <em>GATA2m</em> clustered in zinc finger 2 (ZF2) (77.8 %); higher than the ZF2 mutated cases among <em>SETBP1wt</em>/<em>GATA2m</em> (46.3 %, p = 0.1). Among <em>SETBP1m</em>/<em>GATA2m</em>, 77.8 % of patients had <em>SRSF2</em> co-mutation, compared to 44.8 % among <em>SETBP1m</em>/<em>GATA2wt</em> (p = 0.08), and 27.8 % among <em>SETBP1wt</em>/<em>GATA2m</em> (p = 0.006). AML progression frequency for non-AML cases did not significantly differ between the 3 groups. Survival of <em>SETBP1m/GATA2m</em> patients was not worse compared to <em>SETBP1wt</em>/<em>GATA2m</em> or <em>SETBP1m/GATA2wt</em>.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"155 ","pages":"Article 107734"},"PeriodicalIF":2.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230127","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}

{"title":"Clinical features and treatment response to TKIs in chronic myeloid leukemia patients with atypical BCR::ABL1 transcripts","authors":"Haoren Wang ,&nbsp;Cong Han ,&nbsp;Benfa Gong ,&nbsp;Yuntao Liu ,&nbsp;Kaiqi Liu ,&nbsp;Runxia Gu ,&nbsp;Ying Wang ,&nbsp;Hui Wei ,&nbsp;Yingchang Mi ,&nbsp;Bingcheng Liu ,&nbsp;Jianxiang Wang","doi":"10.1016/j.leukres.2025.107733","DOIUrl":"10.1016/j.leukres.2025.107733","url":null,"abstract":"<div><div>A small percentage (0.3 %-4.6 %) of chronic myeloid leukemia (CML) patients exhibit atypical transcripts with poorly defined clinical implications. To explore the clinical features and treatment response in those patients, this study retrospectively analyzed 52 CML patients with eight types of atypical transcripts. The three most common types were e19a2, e1a2, and e13a3/e14a3. Compared to patients with typical transcripts, those with e19a2 (n = 17) were older, more frequently female, and had elevated platelet levels. Similarly, patients with e1a2 (n = 6) were predominantly female. Regarding treatment response, the lower cumulative rates of complete cytogenetic response (CCyR) by 1 year were seen in patients with e19a2 (41.2 % vs 85.3 %) and e1a2 (16.7 % vs 87.5 %). The probabilities of failure-free survival (FFS) were lower in patients with e19a2 and e1a2. Additionally, the probabilities of progression-free survival (PFS) were lower in patients with e19a2. However, overall survival (OS) was comparable between atypical and typical cohorts, likely attributable to salvage therapy with second-generation TKIs. No differences were found in clinical features, treatment response, and outcomes among patients with e13a3/e14a3 (n = 11). Notably, rare subtypes exhibited diverse disease manifestations, with e8a2 (n = 3) linked to indolent course and e6a2 (n = 2) associated with rapid progression. In general, atypical transcript subtypes define a clinically heterogeneous CML subgroup with differential TKI sensitivity. Patients with e19a2 and e1a2 transcripts exhibit potential resistance to imatinib but achieve similar outcomes to patients with typical transcripts under second-generation TKI therapy.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"155 ","pages":"Article 107733"},"PeriodicalIF":2.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223437","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}

{"title":"A phase 2 study of itacitinib alone or in combination with low-dose ruxolitinib in patients with myelofibrosis","authors":"Moshe Talpaz ,&nbsp;Aaron T. Gerds ,&nbsp;Roger Lyons ,&nbsp;Peter Langmuir ,&nbsp;Deborah Hunter ,&nbsp;Betty Lamothe ,&nbsp;Kevin Hou ,&nbsp;Brandon McMahon","doi":"10.1016/j.leukres.2025.107732","DOIUrl":"10.1016/j.leukres.2025.107732","url":null,"abstract":"<div><h3>Background</h3><div>The Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib has demonstrated efficacy/safety in patients with myelofibrosis; however, not all patients experience optimal and/or stable response, in part owing to dose-limiting toxicities. This phase 2 study evaluated itacitinib (JAK1-selective inhibitor) efficacy/safety alone or combined with low-dose ruxolitinib.</div></div><div><h3>Methods</h3><div>Cohort A received itacitinib 200 mg once daily (QD) plus ruxolitinib at a previous stable dose (≤15 mg total daily dose). Cohort B (previously ruxolitinib-treated) received itacitinib 600 mg QD alone. The primary endpoint was baseline-to-week 24 spleen volume reduction (SVR).</div></div><div><h3>Results</h3><div>Twenty-three patients were enrolled (median age, 71.0 years; intermediate-1/-2 risk, 73.9 %; Cohort A, n = 13; Cohort B, n = 10). Mean (standard deviation) percentage SVR from baseline was +6.9 % (27.5 %) and −3.0 % (34.7 %) in Cohorts A and B at week 24 (primary endpoint), and −1.6 % (14.7 %) and −24.6 % (21.7 %) in Cohorts A and B at week 12. SVR from baseline was achieved by 5 and 3 patients in Cohorts A and B at week 24, and by 9 and 7 patients in Cohorts A and B at week 12. Most common treatment-emergent adverse events (TEAEs) were anemia, diarrhea, and fatigue (each n = 8); most common grade ≥ 3 TEAEs were anemia (n = 6), thrombocytopenia (n = 5), fatigue (n = 3), and diarrhea (n = 2).</div></div><div><h3>Conclusions</h3><div>Overall, 8 of 23 patients enrolled achieved SVR at week 24; larger average changes in SVR at week 12 were observed for itacitinib monotherapy vs. the combination. No unexpected safety signals were observed.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"155 ","pages":"Article 107732"},"PeriodicalIF":2.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281100","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}

{"title":"Assessing the associations of blood metabolites with myelodysplastic syndrome: A bidirectional mendelian randomization study","authors":"Keyue Hu,&nbsp;Yiquan Cheng,&nbsp;Gangfeng Xiao,&nbsp;Xiu Shen,&nbsp;Suying Qian","doi":"10.1016/j.leukres.2025.107723","DOIUrl":"10.1016/j.leukres.2025.107723","url":null,"abstract":"<div><h3>Background</h3><div>Metabolic disorders are a hallmark feature of cancer. However, evidence regarding the causality of circulating metabolites in promoting or preventing myelodysplastic syndrome (MDS) is currently insufficient. We conducted a bidirectional Mendelian randomization analysis (MR) to assess the causal relationship between genetically proxied 1400 blood metabolites and MDS.</div></div><div><h3>Methods</h3><div>In this study, we employed a bidirectional MR framework to explore the potential causal links between blood metabolites and the risk of MDS. Data on blood metabolites were derived from a comprehensive genome-wide association study (GWAS) dataset of European origin. Initial analyses used MDS GWAS data from the GWAS catalog. The pleiotropy, and heterogeneity analysis were applied to confirm the stability of the MR estimates.</div></div><div><h3>Results</h3><div>In a survey of 1400 metabolites, four exhibited statistical significance (P &lt; 0.05) in an inverse variance weighted (IVW) model. Levels of Alpha-hydroxyisovalerate [odds ratio (OR) = 3.157, p &lt; 0.001], Pregnenediol disulfate (C21H34O8S2) [OR = 2.805, p &lt; 0.001] and 1-linoleoyl-GPG (18:2) [OR = 2.756, p &lt; 0.001] were positively causally associated with MDS, while X-18345 [OR = 0.360, p &lt; 0.001] was negatively associated with MDS. On the contrary, MDS did not lead to significant alterations in the levels of the aforementioned four blood metabolites.</div></div><div><h3>Conclusion</h3><div>In this study, a possible causal relationship was established between four blood metabolites and MDS. Among these, three specific blood metabolites were identified as causal factors in the development of MDS and were confirmed as risk factors. Interestingly, an unknown blood metabolite emerged as a protective factor.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"155 ","pages":"Article 107723"},"PeriodicalIF":2.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306817","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}