Leukemia research最新文献

{"title":"Retraction notice to \"Persistent Cdk2 inactivation drives growth arrest of BCR-ABL-expressing cells in response to dual inhibitor of SRC and ABL kinases SKI606\" [Leuk. Res. 31 (2007) 979-987].","authors":"Manuela Mancini, Gianluca Brusa, Elisa Zuffa, Patrizia Corrado, Giovanni Martinelli, Tiziana Grafone, Enza Barbieri, Maria Alessandra Santucci","doi":"10.1016/j.leukres.2026.108312","DOIUrl":"10.1016/j.leukres.2026.108312","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":" ","pages":"108312"},"PeriodicalIF":2.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001717","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":"Venetoclax and azacitidine versus CAG for unfit patients with newly diagnosed acute myeloid leukemia: A propensity score-matched analysis","authors":"Guanghui Chang ,&nbsp;Haitao Gao ,&nbsp;Yan Wei ,&nbsp;Qiang Fu ,&nbsp;Qian Jiang ,&nbsp;Hao Jiang ,&nbsp;Lanping Xu ,&nbsp;Xiaohui Zhang ,&nbsp;Xiaojun Huang ,&nbsp;Feifei Tang","doi":"10.1016/j.leukres.2026.108187","DOIUrl":"10.1016/j.leukres.2026.108187","url":null,"abstract":"<div><div>This study evaluated the clinical efficacy of venetoclax and azacitidine (VEN+AZA) versus CAG (cytarabine, aclarubicin, and granulocyte colony-stimulating factor) for newly diagnosed adult acute myeloid leukemia (AML) unfit patients. There were 248 patients received VEN+AZA and 104 patients received CAG. A PSM (Propensity Score-Matching) was conducted using the nearest neighbor method in a 1:2 ratio to minimize bias. As a result, 170 patients in the VEN+AZA cohort were matched with 85 patients in the CAG cohort. In propensity-matched group, VEN+AZA had higher CRc rate than the CAG (all cohort, 67.9 % vs 55.5 %, P = 0.04), especially for age ≥ 60 y (OR=1.085, P = 0.04), secondary AML(OR=1.802, P = 0.028), ELN intermediate-adverse karyotype(OR=1.33, P = 0.045), <em>DNMT3A</em> mutation (OR=1.32, P = 0.047) and <em>IDH1/2</em> mutation (OR=1.952, P = 0.049), but patients with <em>RUNX1::RUNX1T1</em> (OR=0.25, P = 0.044) favored CAG in CRc rate. The 3-year OS and EFS for VEN+AZA group and CAG group were 49.8 % VS. 49.8 % (P = 0.81) and 34.3 % VS. 31.7 % (P = 0.20). Patients with age ≥ 60 y (EFS, P = 0.032), ECOG≥ 2 (EFS, P = 0.047), secondary AML (OS, P = 0.015; EFS, P = 0.039), ELN intermediate-adverse karyotype (OS, P = 0.034; EFS, P = 0.044), <em>RUNX1</em> mutation (OS, P = 0.003; EFS, P = 0.003) and <em>IDH1/2</em> mutation (EFS, P = 0.039) showed a preference for VEN+AZA regarding OS, and patients with <em>SRSF2</em> mutation favored CAG in OS (P = 0.031).</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"163 ","pages":"Article 108187"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173004","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 trial evidence + real world data: How do we ensure equal access to optimal CLL care","authors":"Moritz Fürstenau,&nbsp;Carsten Utoft Niemann","doi":"10.1016/j.leukres.2026.108184","DOIUrl":"10.1016/j.leukres.2026.108184","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"162 ","pages":"Article 108184"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146191872","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":"Outcomes of patients with R/R FLT3mut+ AML treated with maintenance gilteritinib therapy after hematopoietic stem cell transplantation","authors":"Hsin-An Hou ,&nbsp;Bartlomiej Getta ,&nbsp;Jae-Sook Ahn ,&nbsp;Dina Elsouda ,&nbsp;Juan Ariza ,&nbsp;Cindy Thiow Koon Lim ,&nbsp;Jamie Jung-Hee An","doi":"10.1016/j.leukres.2026.108186","DOIUrl":"10.1016/j.leukres.2026.108186","url":null,"abstract":"<div><div>Patients with acute myeloid leukemia (AML) with <em>FMS</em>-like tyrosine kinase 3 (<em>FLT3</em>) mutations have a poor prognosis, even after hematopoietic stem cell transplantation (HSCT). Targeted maintenance therapy with gilteritinib is now recommended post-HSCT in de novo measurable residual disease-positive <em>FLT3</em>^mut+ AML patients. However, the benefits of post-HSCT gilteritinib maintenance in relapsed and refractory (R/R) disease are less clear. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to collate and describe the body of evidence (from inception of databases to April 29, 2024) assessing the clinical outcomes of gilteritinib post-HSCT therapy in patients with R/R <em>FLT3</em>^mut+ AML. Eight studies (2 randomized controlled; 6 observational) reporting clinical outcomes in a total of 134 adult patients with <em>FLT3</em>^mut+ AML were included in the narrative synthesis. Six were single-arm studies, and 2 included a comparator group without maintenance therapy after transplantation. From time of HSCT, 1- and 2-year overall survival (OS) rates ranged from 72.3 % to 100 % (n = 55) and 55.8 % to 60.0 % (n = 41), respectively, and 1- and 2-year relapse-free survival (RFS) rates were 46.7 %-100.0 % (n = 27) and 46.7 %-80.0 % (n = 13), respectively. Comparative data suggest that gilteritinib as post-HSCT maintenance therapy may improve clinical outcomes of patients with R/R <em>FLT3</em>^mut+ AML versus no gilteritinib maintenance. However, no definite conclusions can be drawn from the limited clinical data available in this setting. Further well-designed studies with uniformity in defining OS and RFS are required to provide further insight into this strategy for the high-risk R/R <em>FLT3</em>^mut+ AML population.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"162 ","pages":"Article 108186"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776833","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":"Expression and signaling patterns of CD180/MD-1 and CD150 in Chronic Lymphocytic Leukaemia (CLL) cells","authors":"Tamar Tsertsvadze ,&nbsp;Kurtis Edwards ,&nbsp;Sarah John-Olabode ,&nbsp;Irina Datikashvili-David ,&nbsp;Ani Bilanishvili ,&nbsp;John Murphy ,&nbsp;Emanuela V. Volpi ,&nbsp;Peter M. Lydyard ,&nbsp;Nina Porakishvili","doi":"10.1016/j.leukres.2026.108169","DOIUrl":"10.1016/j.leukres.2026.108169","url":null,"abstract":"<div><div>Chronic lymphocytic Leukaemia (CLL) is a B-cell malignancy marked by biological heterogeneity, variable progression and survival outcomes. Orphan toll-like receptor CD180 (RP105) complexed with the accessory protein MD-1 and CD150, which belongs to the signalling lymphocyte activation molecule family (SLAMF1), have emerged as an important modulators of CLL cell signaling and fate. However, their functional interplay, remains insufficiently understood.</div><div>This study investigated the surface and intracellular expression of CD180, CD150, and MD-1 in primary CLL cells and the MEC-1 cell line, alongside their downstream signaling responses. Flow cytometric analyses revealed that MD-1 expression is tightly associated with CD180 and CD150 positivity, which may further indicate a role for MD-1 in stabilizing CD180 surface localization.</div><div>Stimulation of MD-1⁺CD180⁺ CLL cells revealed four distinct signaling phenotypes: AKT signalers, p38MAPK signalers, dual signalers, and non-responders. CD150^low cells preferentially activated AKT, whereas CD150^high cells favored p38MAPK signaling, indicating context-dependent modulation of downstream pathways. Notably, stimulation via CD150 alone induced phosphorylation of both AKT and p38MAPK in specific subsets, confirming its independent signaling capacity.</div><div>In synchronized MEC-1 cells, CD180 and MD-1 expression peaked at 48 h, coinciding with enhanced AKT phosphorylation upon combined CD180/CD150 stimulation. These data suggest that the temporal dynamics of CD180 expression modulate the outcome of CD150-driven signaling, indicating a tightly regulated and interdependent interaction.</div><div>Collectively, these findings define a CD180/MD-1/CD150 signaling axis that underlies the intracellular signaling heterogeneity in CLL. The relative expression balance between CD180 and CD150 may steer cells toward pro-survival or stress-associated signaling, providing novel mechanistic insight into CLL biology and identifying candidate biomarkers or therapeutic targets.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"162 ","pages":"Article 108169"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146191871","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":"CPX-351 versus venetoclax plus hypomethylating agents for newly diagnosed acute myeloid leukemia: A systematic review and meta-analysis","authors":"Akihiro Miyashita ,&nbsp;Abdulrahim Mohammed Basendwah ,&nbsp;Henri Fero ,&nbsp;Fahad Alabbas","doi":"10.1016/j.leukres.2026.108179","DOIUrl":"10.1016/j.leukres.2026.108179","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) predominantly affects older adults, with median age at diagnosis being 68–70 years. Selecting an appropriate regimen is important for older patients. CPX-351 demonstrated superior overall survival (OS) compared to 7 + 3 chemotherapy, while venetoclax and azacitidine significantly improved OS and composite remission rate compared to azacitidine alone. However, the optimal regimen in real-world practice remains uncertain. We performed a systematic review and meta-analysis comparing CPX-351 and the combination of venetoclax and hypomethylating agents (Ven/HMA) in newly diagnosed AML. We systematically searched PubMed, Scopus, and Cochrane Central Register of Controlled Trials from inception to January 2026. Eleven retrospective studies comprising 1852 patients comparing CPX-351 and Ven/HMA were included. The weighted mean of median age was 63.5 years in the CPX-351 cohort and 73 years in the Ven/HMA cohort. CPX-351 did not significantly improve OS (hazard ratio [HR] 0.89; 95 % CI 0.76–1.04; p = 0.1486) with median OS being 13.1 months versus 11.6 months in Ven/HMA cohort. There were no differences in the rates of composite remission rate (48.3 % vs 48.4 %; odds ratio [OR] 0.83; 95 % CI 0.58–1.18; p = 0.295), minimal residual disease negative remission (13.5 % vs 33.9 %; OR 0.61; 95 % CI 0.25–1.49; p = 0.281), 30-day mortality, and 60-day mortality. In conclusion, CPX-351 did not demonstrate superiority over Ven/HMA in composite remission rate and OS. Both regimens remain reasonable therapeutic options for older, newly diagnosed AML patients, and prospective comparative studies are needed to better guide treatment selection.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"162 ","pages":"Article 108179"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116577","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":"Favorable outcomes with fludarabine, melphalan, and total-body irradiation 8–12Gy as an intensified conditioning regimen for adult allogeneic HCT","authors":"Tomoyo Kubo ,&nbsp;Hisashi Yamamoto ,&nbsp;Otoya Watanabe ,&nbsp;Yuki Taya ,&nbsp;Aya Nishida ,&nbsp;Shinsuke Takagi ,&nbsp;Kyosuke Yamaguchi ,&nbsp;Kosei Kageyama ,&nbsp;Daisuke Kaji ,&nbsp;Kazuya Ishiwata ,&nbsp;Yuki Asano-Mori ,&nbsp;Go Yamamoto ,&nbsp;Atsushi Wake ,&nbsp;Shuichi Taniguchi ,&nbsp;Naoyuki Uchida","doi":"10.1016/j.leukres.2026.108183","DOIUrl":"10.1016/j.leukres.2026.108183","url":null,"abstract":"<div><div>High-dose total body irradiation (TBI)–containing conditioning regimens remain an important strategy in allogeneic hematopoietic cell transplantation (allo-HCT). We retrospectively analyzed outcomes of adult patients who received Flu/Mel80/TBI 8–12 Gy at a single center. A total of 83 patients underwent their first allo-HCT between 2002 and 2023. The median age was 54 years; acute lymphoblastic leukemia accounted for 53 % of cases, and 45 % proceeded to transplantation in non-remission. Cord blood was used in 90 % of patients. At a median follow-up of 664 days among survivors, the 3-year overall survival (OS) and relapse-free survival (RFS) were 66.5 % and 59.5 %, respectively. The 3-year cumulative incidence of relapse was 24.0 %, and that of non-relapse mortality (NRM) was 16.5 %. In multivariate analysis, disease status at transplantation was the only factor significantly associated with RFS; no variables were significantly associated with OS, relapse, or NRM. Neutrophil engraftment was achieved in all patients, with a median of 16 days. Acute GVHD grade II–IV and III–IV by day 100 occurred in 64.4 % and 15.7 % of patients, respectively. The 3-year incidence of chronic GVHD was 19.4 %. In the cord blood subgroup, pre-engraftment immune reaction (PIR) occurred in 76 % of patients. In this high-risk cohort with a large proportion of non-remission, the Flu/Mel80/TBI 8–12 Gy regimen resulted in favorable engraftment, low relapse, and acceptable toxicity. These findings suggest that this intensified TBI-based conditioning may represent a viable option for patients requiring strong antitumor activity.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"162 ","pages":"Article 108183"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116578","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":"Clonal hematopoiesis and age-associated degenerative disorders","authors":"Ioannis Chanias ,&nbsp;Michael Doulberis ,&nbsp;Nicolas Bonadies","doi":"10.1016/j.leukres.2026.108180","DOIUrl":"10.1016/j.leukres.2026.108180","url":null,"abstract":"<div><div>Clonal hematopoiesis (CH) is increasingly recognized not only as a predisposing factor for overt hematologic malignancies but also as a contributor to cardiovascular, metabolic, and other age-associated degenerative and inflammatory disorders. These associations likely arise from complex heterotypic interactions between clonally affected and non-clonal immune cells, leading to systemic immune dysregulation and chronic inflammation that affects multiple organ systems, most prominently the cardiovascular system. Somatic mutations typically linked to myeloid neoplasms disturb the inflammatory homeostasis of hematopoietic and immune compartments, resulting in a persistently heightened inflammatory state and exaggerated responses under stress conditions. Pattern-recognition receptors (PRRs) of the innate immune system detect pathogen- or damage-associated molecular patterns and activate supramolecular organizing centers (SMOCs) and downstream signaling cascades—including the inflammasome, myddosome, trifosome, necroptosome, and the TGF-β pathway—that drive the production of pro-inflammatory cytokines such as IL-1β, TNF-α, IFN-I, and IL-6. Recent studies have begun to elucidate the mechanisms by which CH-associated mutations confer clonal advantage and dysregulate inflammatory signaling, bridging hematologic and degenerative diseases. A better understanding of these mechanistic links may facilitate the development of targeted therapies aimed at curbing clonal evolution and mitigating inflammation-driven comorbidities. In this review, we summarize the current knowledge on CH, its impact on immune dysregulation, and emerging therapeutic opportunities.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"162 ","pages":"Article 108180"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132082","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":"T-cell mixed chimerism after allogeneic hematopoietic stem cell transplantation does not correlate with relapse in patients with acute myeloid leukemia","authors":"Wei J. Wang,&nbsp;Sa A. Wang,&nbsp;Gheath Al-Atrash,&nbsp;Hong Fang,&nbsp;Shimin Hu,&nbsp;Shaoying Li,&nbsp;Jie Xu,&nbsp;Qing Wei,&nbsp;L. Jeffrey Medeiros,&nbsp;Wei Wang","doi":"10.1016/j.leukres.2026.108185","DOIUrl":"10.1016/j.leukres.2026.108185","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"162 ","pages":"Article 108185"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146191448","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":"The effect of IL-4 on CD180 expression and signalling in Chronic lymphocytic leukaemia (CLL)","authors":"Ani Bilanishvili ,&nbsp;Tamar Tsertsvadze ,&nbsp;Kurtis Edwards ,&nbsp;Sarah John-Olabode ,&nbsp;Uzma Syed ,&nbsp;Irina Datikashvili-David ,&nbsp;Emanuela V. Volpi ,&nbsp;John Murphy ,&nbsp;Peter M. Lydyard ,&nbsp;Nina Porakishvili","doi":"10.1016/j.leukres.2026.108166","DOIUrl":"10.1016/j.leukres.2026.108166","url":null,"abstract":"<div><div>Chronic lymphocytic leukaemia (CLL) progression is critically dependent on tumour microenvironment (TME) signals, including those regulated via toll-like receptors (TLRs) that drive CLL cell survival and proliferation. We have previously shown that CD180, an orphan TLR is expressed on the surface in approximately 60 % of CLL samples, and that heterogeneity of CD180 cell surface expression and signalling impacts CLL cell survival, proliferation, and apoptosis. Interleukin-4 (IL-4), a cytokine abundantly present in the CLL microenvironment, is a well-documented pro-survival factor for CLL cells. IL-4 has also been shown to enhance sIgM expression and function by subsequent downstream signalling in a JAK3/STAT6 dependent manner within CLL samples. In this study, we investigated the impact of IL-4 on CD180 expression, CD180-mediated signalling and apoptosis of CLL cells and cell lines MEC-1 and RAMOS. Our results demonstrate that IL-4 enhances CD180 surface expression in CLL cells and RAMOS cell line, affecting downstream signalling pathways that alter CLL cell survival through the activation of AKT and p38MAPK. MEC-1 cells exhibited a less pronounced and variable response. These findings highlight the IL-4/CD180 axis as an important modulator of CLL, altering cell signalling dynamics.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"161 ","pages":"Article 108166"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981906","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}