Leukemia research最新文献

{"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}

{"title":"Calcium channel blocker use is associated with longer time to first post transfusion cardiac event in lower risk MDS","authors":"Carissa S.Y. Chan ,&nbsp;Heather A. Leitch","doi":"10.1016/j.leukres.2026.108171","DOIUrl":"10.1016/j.leukres.2026.108171","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"161 ","pages":"Article 108171"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024968","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":"Juggling two worlds: Exploring the experiences of caregivers of patients with acute leukemia","authors":"Maya A. Stern ,&nbsp;Elizaveta Klekovkina ,&nbsp;Stephanie M. Nanos ,&nbsp;Esme Fuller-Thomson ,&nbsp;Carmine Malfitano","doi":"10.1016/j.leukres.2025.108154","DOIUrl":"10.1016/j.leukres.2025.108154","url":null,"abstract":"<div><h3>Purpose</h3><div>Caregiver burden is an often reported consequence of caring for patients with acute leukemia (AL). The current literature extensively describes caregiving tasks for patients with AL but provides limited information about the challenge of balancing these new obligations with previous and concurrent personal and family responsibilities. The goal of this qualitative study was to understand the multifaceted responsibilities of caregivers of patients with AL, their perceived impact, and the available resources that these caregivers found to be supportive in their caregiving role.</div></div><div><h3>Methods</h3><div>A secondary analysis, using qualitative description, was conducted on data obtained from interviews with 21 caregivers of children and adults with AL.</div></div><div><h3>Results</h3><div>Caregivers described balancing many responsibilities related to the patient, other relationships, work, and home. Coordinating and multitasking responsibilities were perceived to have an adverse effect on the emotional, physical, and financial well-being of participants. Social support was identified as a resource that supported the ability to manage the diverse responsibilities, and caregivers provided emotional and practical suggestions for care.</div></div><div><h3>Conclusions</h3><div>Upon becoming a caregiver for a patient with AL, individuals are faced with new responsibilities that compound their existing obligations, often resulting in the de-prioritization of the caregiver’s needs and other responsibilities. The development and implementation of caregiver support as a standard of care is necessary to mitigate the negative consequences of caregiving.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"161 ","pages":"Article 108154"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145944894","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":"Impact of autoimmune diseases or inflammatory manifestations on response and outcome in high-risk myelodysplastic syndromes and chronic myelomonocytic leukemia","authors":"Rinzine Sammut,&nbsp;Antoine Benichou,&nbsp;Chen Wang,&nbsp;Michael Loschi,&nbsp;Sami Benachour,&nbsp;Valentine Richez-Olivier,&nbsp;Edmond Chiche,&nbsp;Rami Komrokji,&nbsp;Corinne Ferrero-Vacher,&nbsp;Neila De Pooter,&nbsp;Joy Mouanes-Abelin,&nbsp;Bérengere Dadone-Montaudie,&nbsp;David A. Sallman ,&nbsp;Thomas Cluzeau","doi":"10.1016/j.leukres.2026.108168","DOIUrl":"10.1016/j.leukres.2026.108168","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"161 ","pages":"Article 108168"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011081","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":"Single cell transcriptomics derived combinatorial markers distinguished leukemic stem cells from hematopoietic stem cells in acute myeloid leukemia","authors":"Aafreen Khan ,&nbsp;Smeeta Gajendra ,&nbsp;Vivek Kumar Singh ,&nbsp;Deepshi Thakral ,&nbsp;Sameer Bakhshi ,&nbsp;Ranjit Kumar Sahoo ,&nbsp;Rachna Seth ,&nbsp;Sandeep Rai ,&nbsp;Ritu Gupta","doi":"10.1016/j.leukres.2026.108170","DOIUrl":"10.1016/j.leukres.2026.108170","url":null,"abstract":"<div><div>Leukemic stem cells (LSCs) play a critical role in relapse and chemoresistance in acute myeloid leukemia (AML). These LSCs originate from Hematopoietic stem cells (HSCs) after acquiring genetic and molecular aberrations. Both HSCs and LSCs predominantly reside in CD34 +CD38- fraction of the bone marrow and their phenotypic similarities poses a challenge in distinguishing between them. In addition, the phenotypic heterogeneity of LSCs limits the precise quantitation of this population in clinical studies. Delineation of LSCs from HSCs and quantification of LSC burden is crucial as it is correlated with survival rates and treatment outcomes in AML. In this study, we employed single cell transcriptomic analysis to identify differentially expressed cell surface markers that can discriminate LSCs from HSCs. Our data revealed several candidate markers, including CD48, CD52, CD96 and CD88 with distinct expression patterns in LSCs compared to HSCs. We further validated the expression levels of these markers as potential biomarkers for the identification of LSCs in both CD34 + and CD34- AML. Among these cell surface markers, CD52, CD96 and CD48 were significantly over-expressed in LSCs relative to HSCs. Incorporating these markers in combination with established aberrant markers can enhance the identification of LSCs and help distinguish them from HSCs in both CD34 + and CD34- AML. Our findings support the use of an expanded combinatorial marker panel and warrants its further evaluation in a larger AML cohort, particularly in the context of measurable residual disease (MRD) assessment, prognostication and correlation with treatment response and survival outcomes.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"161 ","pages":"Article 108170"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024967","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 utility of interim bone marrow biopsies in FLT3 mutant acute myeloid leukemia","authors":"Vincent Lok,&nbsp;Katie Moffitt,&nbsp;Dahniel Sastow,&nbsp;Georgio Medawar,&nbsp;Su Bin Hahn,&nbsp;Preston Perez,&nbsp;Abigail Demers,&nbsp;Alexander Coltoff,&nbsp;Douglas Tremblay,&nbsp;Joshua Zeidner,&nbsp;David M. Swoboda","doi":"10.1016/j.leukres.2025.108147","DOIUrl":"10.1016/j.leukres.2025.108147","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"161 ","pages":"Article 108147"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024969","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, treatment pathway and resource utilisation for patients with chronic lymphocytic leukaemia: A multicentre retrospective study","authors":"Ahmad Alhuraiji ,&nbsp;Ayman Alhejazi ,&nbsp;Bhausaheb Bagal ,&nbsp;Chee Yen Lin ,&nbsp;Efreen Montaño ,&nbsp;Macarena Roa ,&nbsp;Miguel Pavlovsky ,&nbsp;Mohamed Samra ,&nbsp;Shang-Ju Wu ,&nbsp;Veena Selvaratnam ,&nbsp;Ayman Elsayes ,&nbsp;Mohamed Elsayed ,&nbsp;Amgad Kamal ,&nbsp;K. Pushpalata ,&nbsp;Akemi Ishikawa ,&nbsp;Francisco Gonzalez","doi":"10.1016/j.leukres.2025.108152","DOIUrl":"10.1016/j.leukres.2025.108152","url":null,"abstract":"<div><h3>Introduction</h3><div>This study describes the clinical characteristics, treatment pathways, and resource utilisation of patients with chronic lymphocytic leukaemia (CLL) across multiple regions.</div></div><div><h3>Methods</h3><div>This retrospective, observational, registry-based study included patients diagnosed with CLL who started treatment for at least 12 months before data collection (November 2021 to March 2023). Patients were recruited from multiple centres across Asia, Australia, Latin America, and the Middle East and North Africa. A pilot cohort was included to describe the clinical characteristics of treatment-naïve CLL patients.</div></div><div><h3>Results</h3><div>The study included 886 patients in the CLL-treated and 123 in the treatment-naïve cohorts. The mean age was nearly 63 years in both cohorts, with a majority being male. There was low utilisation of risk scores (74–76.9 % of the patients had no available scores). The Rai staging showed that the majority of the treatment-naïve cohort was in stage 0 (60.6 %), while the CLL-treated cohort had a more even distribution across all stages. The Cumulative Illness Rating Scale score showed that 60.9 % of the CLL-treated cohort had a score of ≥ 6, compared to 58.5 % in the treatment-naïve cohort. The Fluorescence in situ hybridisation (FISH)-based prognosis was available for 41.2 % of the CLL-treated cohort and 56.9 % of the treatment-naïve cohort. The cytogenetic testing was available for only 18.7 % of the CLL-treated cohort. The chemoimmunotherapy (CIT) regimens were the most commonly prescribed regimen, with a median first-line progression-free survival (PFS) of 26.1 months (95 % CI: 13.8, 42.8). Targeted therapies in the first-line setting were used by 20.2 % of patients. For first-line therapy, the objective response rate for CIT was 53.2 % (95 % CI: 49.5 %, 57 %), compared to 56.4 % (95 % CI: 49.2 %, 63.7 %) for targeted therapies. Patients receiving CIT had significantly higher rates of adverse events, inpatient hospitalisations, longer hospital stays, and a greater need for blood transfusions.</div></div><div><h3>Conclusion</h3><div>The present global study demonstrates the regional variations in the presentation and outcomes of CLL. A considerable number of patients with CLL present with advanced disease staging at diagnosis; still, the utilisation of genetic testing is low despite the plethora of approved targeted therapy.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"160 ","pages":"Article 108152"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839659","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":"Frequency and prognostic significance of RAS pathway alterations in adult acute lymphoblastic leukemia","authors":"Jiawang Ou ,&nbsp;Jia Li ,&nbsp;Qifa Liu ,&nbsp;Hongsheng Zhou","doi":"10.1016/j.leukres.2025.108155","DOIUrl":"10.1016/j.leukres.2025.108155","url":null,"abstract":"<div><h3>Summary</h3><div><em>RAS</em> pathway alterations play an important role in the development and progression of hematological malignancies. However, their frequency and clinical significance in adult ALL remain poorly investigated and not well defined. In this study, we analyzed the frequency and prognostic significance of <em>RAS</em> pathway alterations in newly diagnosed adult ALL patients. Among the 387 patients, <em>RAS</em> pathway alterations were detected in 52 (13.4 %). Multivariate analysis identified these alterations as independent predictors of poor overall survival (OS) and event-free survival (EFS) (OS, <em>P</em> = 0.046; EFS, <em>P</em> = 0.004). Kaplan-Meier survival analysis revealed that patients with <em>PTPN11</em> mutations had poorer OS (<em>P</em> = 0.029) than those without <em>PTPN11</em> mutations. Patients with <em>KRAS</em> mutations had inferior OS and EFS compared to those without <em>KRAS</em> mutations (<em>P</em> = 0.021; 0.0017). These findings suggest that analysis of <em>RAS</em> pathway alterations may enable more accurate prognostic stratification of adult ALL patients.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"160 ","pages":"Article 108155"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827965","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":"Frequency and clinical impact of acute kidney injury in haploidentical hematopoietic cell transplantation with post-transplantation cyclophosphamide","authors":"Toshihide Endo ,&nbsp;Hiromichi Takahashi ,&nbsp;Takahiro Namiki,&nbsp;Yoshiyuki Hayashi,&nbsp;Shun Ito,&nbsp;Hironao Nukariya,&nbsp;Kazuya Kurihara,&nbsp;Takashi Koike,&nbsp;Yuuichi Takeuchi,&nbsp;Takashi Hamada,&nbsp;Kazuhide Iizuka,&nbsp;Shimon Otake,&nbsp;Masaru Nakagawa,&nbsp;Hideki Nakamura,&nbsp;Katsuhiro Miura","doi":"10.1016/j.leukres.2025.108143","DOIUrl":"10.1016/j.leukres.2025.108143","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"160 ","pages":"Article 108143"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621992","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":"Identification and characterization of peptidyl-prolyl isomerase Pin1 as a new regulatory component of BCR::ABL1 degradation","authors":"Fujiko Tsukahara ,&nbsp;Kenjiro Kaji,&nbsp;Yoshiro Maru","doi":"10.1016/j.leukres.2025.108146","DOIUrl":"10.1016/j.leukres.2025.108146","url":null,"abstract":"<div><div>While tyrosine kinase inhibitors (TKIs) can effectively counteract BCR::ABL1 activity, resistance by BCR::ABL1 overexpression is a significant challenge in combating chronic myeloid leukemia, making down-regulation of BCR::ABL1 a promising anti-cancer strategy. We previously reported that the ubiquitin ligases c-Cbl and CHIP mediate BCR::ABL1 protein degradation. Bag1, a nucleotide exchange factor for Hsc70, senses immature structures of Hsp90-unchaperoned BCR::ABL1 protein and stimulates CHIP-induced BCR::ABL1 degradation. Peptidyl-prolyl cis/trans isomerases (PPIases) have been shown to regulate protein conformations for stability and degradation, while nothing is known about the PPIases for BCR::ABL1. Here we identified the parvulin-type Pin1 as a new regulatory component of BCR::ABL1 degradation system. Among several PPIases tested, we found that Pin1 specifically binds to BCR::ABL1 protein for degradation. Using a series of BCR::ABL1 mutants, we identified the SH2-binding domain of BCR portion as the Pin1 binding region. The Pin1 WW domain appears to associate with the one or more S/T-Pro motif(s) in the SH2 binding region of BCR::ABL1. Pin1 stimulates not only Hsp90 inhibitor- but also PP2A-induced protein degradation. We also found that Pin1 effectively inhibited TKI-induced BCR::ABL1 stabilization. Pin1 may convert the mature form BCR::ABL1 to an immature form for Bag1 recognition leading to CHIP-mediated ubiquitination and degradation. These findings may lead to provide a molecular basis for the development of new Pin1 related therapeutic strategies against TKI resistance.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"160 ","pages":"Article 108146"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145724317","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}