Leukemia research最新文献

{"title":"Comprehensive analysis of tyrosine kinase domain mutations and imatinib resistance in chronic myeloid leukemia patients","authors":"Somprakash Dhangar ,&nbsp;Chandrakala Shanmukhaiah ,&nbsp;Jagdeeshwar Ghatanatti ,&nbsp;Leena Sawant ,&nbsp;Nehakumari Maurya ,&nbsp;Babu Rao Vundinti","doi":"10.1016/j.leukres.2025.107679","DOIUrl":"10.1016/j.leukres.2025.107679","url":null,"abstract":"<div><div>Tyrosine kinase domain mutations (TKDMs) plays an important role in prognosis of chronic myeloid leukemia (CML). The aim of the present study was to identify the TKDMs associated with imatinib mesylate (IM) drug resistant in CML, following European leukemia Net (ELN) guidelines. Direct sequencing analysis revealed point mutations in 69.44 % (50/72), compound/ polyclonal mutations in 11.11 % (8/72) and large deletions in 4.16 % (3/72) of IM non-responder CML patients. Additionally, we have identified low level mutations in 30.55 % of warning group patients through NGS analysis, that include singly occurring point mutations (5) and polyclonal (6) mutations with mutant allele frequency ranging from 1.1 % to 14.70 %. The low-level mutations detected through NGS in warning group patients; may be responsible for suboptimal response in our study. However, follow-up studies are important to understand the mechanism of clonal evolution. We also identified 5 novel mutations that had not been reported in public databases which expands the spectrum of known mutations in <em>BCR::ABL1</em> fusion gene. Our study also highlighted the impact on patient outcomes following the implementation of ELN guidelines underscores the importance of adherence to standardized protocols in clinical practice.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"152 ","pages":"Article 107679"},"PeriodicalIF":2.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670305","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":"Stratagems of HTLV-1 for persistent infection and the resultant oncogenesis: Immune evasion and clonal expansion","authors":"Takafumi Shichijo,&nbsp;Jun-ichirou Yasunaga","doi":"10.1016/j.leukres.2025.107680","DOIUrl":"10.1016/j.leukres.2025.107680","url":null,"abstract":"<div><div>Adult T-cell leukemia-lymphoma (ATL) is one of the most severe malignant T-cell leukemia/lymphomas induced by human T-cell leukemia virus type I (HTLV-1). HTLV-1 persists in the host through stratagems of proliferating infected cells and evading host immunity. HTLV-1 encodes two viral oncogenes, <em>tax</em> and <em>HTLV-1 bZIP factor (HBZ)</em>, which are related with protection from cell death and promotion of cell proliferation. In addition, <em>HBZ</em> and the somatic mutations in host genes, such as <em>C-C chemokine receptor 4</em> (<em>CCR4)</em> and <em>CIC</em>, convert HTLV-1–infected cells into regulatory T (Treg)-like cells, leading to evasion of host immunity. A recent study demonstrated the key mechanisms for clonal expansion of HTLV-1–infected cells; the activation of the transforming growth factor (TGF)-β signaling pathway by HBZ not only converts HTLV-1–infected cells into a Treg-like cells through <em>Foxp3</em> expression, but also contributes to the proliferation of HTLV-1–infected cells themselves. Due to the longevity induced by HTLV-1 infection, somatic mutations and epigenetic aberrations are accumulated in infected clones, contributing to the oncogenesis of ATL. Collectively, the long-term survival of infected cells enabled by the HTLV-1’s stratagems for persistent infection ultimately leads to ATL oncogenesis via the accumulation of genetic/epigenetic abnormalities.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"152 ","pages":"Article 107680"},"PeriodicalIF":2.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687909","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 and therapeutic significance of genetic profiling in adult T-cell leukemia/lymphoma","authors":"Yasunori Kogure ,&nbsp;Keisuke Kataoka","doi":"10.1016/j.leukres.2025.107676","DOIUrl":"10.1016/j.leukres.2025.107676","url":null,"abstract":"<div><div>Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive T-cell malignancy with a poor prognosis. Several genetic analyses using next-generation sequencing have uncovered recurrent mutations and copy number alterations involved in diverse functional pathways, including T-cell receptor/NF-κB signaling, immune surveillance, transcription factors, chemokine receptors, and CIC-ATXN1 complex. In addition to these alterations, recurrent structural variations, including <em>PD-L1</em> (<em>CD274</em>) and <em>REL</em> truncations, characterize ATLL genome. Recent clinicogenetic studies have linked several genetic alterations, such as <em>PRKCB</em> mutations, to a worse clinical outcome. Using genetic and clinical factors, novel prognostic models have been developed, which outperform previous models based on only clinical factors in prognostic prediction. Furthermore, genetic and epigenetic events influencing response to molecularly targeted therapies, such as mogamulizumab and valemetostat, have also been identified. Collectively, these insights underscore the clinical importance of assessing genetic alterations. This review highlights the latest insights into the genetic landscape of ATLL and their clinical implications, which will facilitate the development of future strategies for targeted and personalized therapy.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"151 ","pages":"Article 107676"},"PeriodicalIF":2.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561766","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 triple-class refractory multiple myeloma patients at a single clinic: A retrospective study","authors":"Ryan Danis ,&nbsp;Sean Bujarski ,&nbsp;David Yashar ,&nbsp;Ashley Del Dosso ,&nbsp;Jonathan Moore ,&nbsp;Sarah Mettias ,&nbsp;James R. Berenson","doi":"10.1016/j.leukres.2025.107677","DOIUrl":"10.1016/j.leukres.2025.107677","url":null,"abstract":"<div><h3>Background</h3><div>Multiple myeloma (MM) is an incurable B cell malignancy requiring complex treatments with a variety of drugs. Patients often become refractory to proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies (mAb), and termed triple class refractory (TCR), associated with a poor prognosis.</div></div><div><h3>Objective</h3><div>We performed a retrospective analysis of data regarding the outcomes of TCR MM patients at a single clinic specializing in the care of multiple myeloma patients.</div></div><div><h3>Patients and methods</h3><div>A retrospective chart review was conducted among 117 patients with TCR MM at a single clinic. Patients’ progression-free survival (PFS), overall survival (OS), cytogenetics, lines of prior therapy (LOT), and first treatment they received after the development of TCR disease were determined.</div></div><div><h3>Results</h3><div>The median time from diagnosis to development of TCR disease from diagnosis was 47 months (range: 1.5–191.0; n = 104) and the median LOT prior to TCR disease development was 5 (range: 2–13; n = 117). From the development of TCR disease, patients in our study showed a median OS of 18.9 months (range: 0.03–60.0) and a median PFS of 3.1 months (range: 0.1–55.1). The most commonly utilized first treatment regimens used after TCR disease development were mAb-containing combinations (n = 42). Venetoclax-based regimens showed the longest median PFS at 12.4 months (n = 14).</div></div><div><h3>Conclusions</h3><div>This median OS of 18.9 months recorded at a single clinic provides real-world data regarding the survival of TCR MM patients highlighting the need for improvement in prognosis for this subset of patients.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"151 ","pages":"Article 107677"},"PeriodicalIF":2.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529813","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 impact of the solute carrier gene superfamily polymorphisms on tyrosine kinase inhibitors responses among chronic myeloid leukemia: A meta-analysis","authors":"Vu Thi Thuy ,&nbsp;Nguyen Linh Viet ,&nbsp;Nguyen Trong Nghia ,&nbsp;Giovanni Cangelosi ,&nbsp;Fabio Petrelli ,&nbsp;Cuc Thi Thu Nguyen","doi":"10.1016/j.leukres.2025.107673","DOIUrl":"10.1016/j.leukres.2025.107673","url":null,"abstract":"<div><h3>Background</h3><div>Tyrosine kinase inhibitors (TKIs) are currently the first-line therapy for chronic myeloid leukemia (CML), but proportion of treatment responses may be influenced by genetic polymorphisms, especially, the solute carrier gene superfamily (SLC). This study was conducted to evaluate the relationship of polymorphisms in the SLC genes family and treatment responses to TKIs among CML patients.</div></div><div><h3>Methods</h3><div>A systematic search was conducted from four databases, including PubMed, Cochrane Library, Embase and Web of Science, up to March 2023. The relationship between SLC polymorphisms and TKI efficacy was assessed by pooled odds ratios (ORs) of the complete cytogenetic response (CCyR) and major molecular biological response (MMR) with 95 % confidence intervals (95 %CIs) across five genetic models (dominant, recessive, homozygote, heterozygote, and allele). Meta-analyses, heterogeneity between studies, publication bias, sensitivity, meta-regression and subgroup analysis were all performed.</div></div><div><h3>Results</h3><div>A total of 19/983 studies meeting the criteria were included in the meta-analysis, with eight variants belonging to three genes (SLC22A1, SLCO1B3, and SLC22A4). The results showed that there was a statistically significant association between the SLC22A1 rs683369 variant and a lower rate of achieving MMR in all 05 genetic models. Similar results were also recorded in the dominant and homozygote models of the SLC22A1 rs628031 variant (OR= 0.61 (95 %CI= 0.46–0.82); OR= 0.46 (95 %CI= 0.23–0.94), respectively); particularly in Asian patients. No relationship was identified between MMR and other genes, as well as that of CCyR and all variants.</div></div><div><h3>Conclusion</h3><div>SLC variants can be predictive signals of imatinib responses among CML; Asian patients should be paid attention during the treatment.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"151 ","pages":"Article 107673"},"PeriodicalIF":2.1,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552149","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":"Complementing therapeutic strategies for acute myeloid leukemia: Signaling pathways and targets of traditional Chinese medicine","authors":"Qiaoliang Wu ,&nbsp;Lei Zhong ,&nbsp;Guibing Zhang ,&nbsp;Liying Han ,&nbsp;Jing Xie ,&nbsp;Yao Xu","doi":"10.1016/j.leukres.2025.107672","DOIUrl":"10.1016/j.leukres.2025.107672","url":null,"abstract":"<div><div>Leukemia is a heterogeneous malignant tumor of the hematopoietic system and is characterized by the blockage of differentiation and uncontrolled proliferation of myeloid or lymphoid progenitor cells in the bone marrow and peripheral blood. Currently, intensified chemotherapy regimens and hematopoietic stem cell transplantation (HSCT) are the most common treatment methods for various types of leukemia. However, they are associated with severe side effects and multidrug resistance. Therefore, developing new treatment approaches with sufficient therapeutic effects to eliminate leukemia cells and improve leukemia outcomes selectively is essential. Traditional Chinese Medicine (TCM) has received widespread attention as an alternative treatment for acute myeloid leukemia (AML) because of its multi-component and multi-target characteristics. Increasing evidence suggests that TCM blocks AML progression by regulating various biological processes. Herein, we review the effects of TCM therapies for AML and its potential mechanisms and targets. Our findings will promote further research and improve the clinical application of TCM in treating AML.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"151 ","pages":"Article 107672"},"PeriodicalIF":2.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520979","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":"Molecular genetic characterization of mixed-phenotype acute leukemia (MPAL) with BCR::ABL1 fusion","authors":"Sophia Shi ,&nbsp;Qianghua Zhou ,&nbsp;Davidson Zhao ,&nbsp;Mojgan Zarif ,&nbsp;Cuihong Wei ,&nbsp;Hassan Sibai ,&nbsp;Hong Chang","doi":"10.1016/j.leukres.2025.107665","DOIUrl":"10.1016/j.leukres.2025.107665","url":null,"abstract":"<div><h3>Background</h3><div>Mixed-phenotype acute leukemia with <em>BCR::ABL1</em> fusion (MPAL^{<em>BCR::ABL1</em>}), previously known as Philadelphia chromosome-positive mixed phenotype acute leukemia, is a heterogeneous group that is segregated into different subtypes based on WHO-HAEM5. The genetic profile of MPAL^{<em>BCR::ABL1</em>} remains poorly defined due to its rarity.</div></div><div><h3>Methods</h3><div>We conducted a retrospective study of 16 patients with MPAL^{<em>BCR::ABL1</em>} and compared their clinical and laboratory profiles to 20 patients with AML^{<em>BCR::ABL1</em>}.</div></div><div><h3>Results</h3><div>Compared to patients with AML^{<em>BCR::ABL</em>} with a median age of 64 years old<em>,</em> patients with MPAL^{<em>BCR::ABL1</em>} were significantly younger at a median of 47 years old (P = 0.031) with similar white blood cell (WBC) count, hemoglobin (Hb) count, platelet (PLT) count, lactate dehydrogenase (LDH) levels, and bone marrow blast percentage. MPAL^{<em>BCR::ABL1</em>} patients harboured a similar frequency of co-occurring additional cytogenetic abnormalities (ACA) compared to AML^{<em>BCR::ABL1</em>} with monosomy 7 (25 %) being the most common ACA in MPAL^{<em>BCR::ABL1</em>}. The most commonly mutated gene in MPAL^{<em>BCR::ABL1</em>} patients was <em>RUNX1</em> at 45 %. The overall survival (OS) and event-free survival (EFS) between MPAL^{<em>BCR::ABL1</em>} and AML^{<em>BCR::ABL1</em>} significantly differed, conferring a better prognosis for patients with MPAL^{<em>BCR::ABL1</em>}.</div></div><div><h3>Conclusion</h3><div>Our results indicate that adult patients with MPAL^{<em>BCR::ABL1</em>} present with younger age and may have better survival outcomes than patients with AML^{<em>BCR::ABL1</em>}. In addition, our next-generation sequencing (NGS) data indicates that <em>RUNX1</em> is frequently mutated in B/myeloid MPAL^{<em>BCR::ABL1</em>} compared to AML^{<em>BCR::ABL1</em>}. Future studies are warranted to further elucidate the role of <em>RUNX1</em> in this disease.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"151 ","pages":"Article 107665"},"PeriodicalIF":2.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510317","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":"Myelodysplastic neoplasm with del(11q). Rara Avis.","authors":"Robert Peter Gale","doi":"10.1016/j.leukres.2025.107664","DOIUrl":"10.1016/j.leukres.2025.107664","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"150 ","pages":"Article 107664"},"PeriodicalIF":2.1,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454543","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":"Sparsity regularization enhances gene selection and leukemia subtype classification via logistic regression","authors":"Nozad Hussein Mahmood ,&nbsp;Dler Hussein Kadir","doi":"10.1016/j.leukres.2025.107663","DOIUrl":"10.1016/j.leukres.2025.107663","url":null,"abstract":"<div><div>This study investigated the application of sparsity regularization methods to improve the classification of leukemia subtypes using high-dimensional gene expression data. Multinomial logistic regression models with the sparsity methods of Ridge, Lasso, and Elastic Net regularizations were employed to address overfitting and dimensionality issues while enhancing model interpretability. The study used a leukemia cancer dataset from the Curated Microarray Database (CuMiDa), which included gene expression data for 16,383 genes across 281 samples representing seven different types of leukemia. The statistical metrics of Accuracy, Kappa statistics, AUC, and F1-score were used to measure the models' implementation. Besides, the effectiveness and ability of each method in gene selection and dimensional reduction of the models were discussed. Elastic Net regularization was a better technique than the Ridge and Lasso based on overall classification performance; it also reached the highest accuracy along with Kappa values. On the other hand, both Lasso and Elastic Net were making more effective feature selections, creating sparse models that could efficiently discriminate leukemia subtypes. In this way, the results highlighted that the inclusion of sparsity regularization could enhance knowledge and accuracy in such a challenging task of subclass leukemia classification, enabling much more tailored treatments.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"150 ","pages":"Article 107663"},"PeriodicalIF":2.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420941","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":"Characteristics and survival outcomes of patients with myelodysplastic syndromes with isolated 11q deletion","authors":"Kensuke Takaoka ,&nbsp;Rami Komrokji ,&nbsp;Kelly Chien ,&nbsp;Guillermo Montalban-Bravo ,&nbsp;Julie Braish Salman ,&nbsp;Samuel Urrutia ,&nbsp;Alex Bataller ,&nbsp;Alexandre Bazinet ,&nbsp;Jeannot Kekedjian ,&nbsp;Najla H. Al Ali ,&nbsp;David Sallman ,&nbsp;Eric Padron ,&nbsp;Zhuoer Xie ,&nbsp;Rashmi Kanagal-Shamanna ,&nbsp;Guilin Tang ,&nbsp;Hui Yang ,&nbsp;Juan Jose Rodriguez-Sevilla ,&nbsp;Guillermo Garcia-Manero ,&nbsp;Koji Sasaki","doi":"10.1016/j.leukres.2025.107661","DOIUrl":"10.1016/j.leukres.2025.107661","url":null,"abstract":"<div><div>Myelodysplastic syndrome (MDS) with isolated deletion 11q is a rare favorable cytogenetic abnormality with a low risk of progression to acute myeloid leukemia (AML). The aim of this study is to describe the clinical characteristics and long-term outcomes of patients with isolated del(11q) MDS. Between August 1997 and January 2024, 52 patients with MDS and isolated del(11q) were diagnosed, representing 0.4 % of the cohort. The median age was 69 years, with a mild male predominance (62 %). By the World Health Organization (WHO) 2022, 42 % of patients had MDS with low blasts. With a median follow-up of 96 months, the median survival was 71 months with a 5-year survival rate of 53 %. The 5-year survival rates were 45 % and 68 % in the hypomethylating agents and best supportive care group, respectively (P = 0.63). Multivariate Cox regression analyses identified age, absolute neutrophil count, hemoglobin, and blast percentages as significant prognostic factors. Despite isolated del(11q) MDS being classified as a very-good-risk cytogenetic abnormality, long-term survival is poor with the risk of progression to AML and complications from cytopenias. The poor long-term survival indicates the need for the investigation of effective supportive care and early intervention to benefit patients with lower-risk MDS and high-risk features.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"150 ","pages":"Article 107661"},"PeriodicalIF":2.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387024","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}