Leukemia research最新文献

{"title":"The role of morphology in diagnosing MDS with Non-clonal cytopenias","authors":"Gentiana Elena Trotta ,&nbsp;Enrico Santinelli ,&nbsp;Sabrina Mariani ,&nbsp;Katia Paciaroni ,&nbsp;Tommaso Caravita di Toritto ,&nbsp;Natalia Cenfra ,&nbsp;Susanna Fenu ,&nbsp;Paola Ricci ,&nbsp;Luca Maurillo ,&nbsp;Federico Moretti ,&nbsp;Emiliano Fabiani ,&nbsp;Carmelo Gurnari ,&nbsp;Maria Teresa Voso ,&nbsp;on behalf of Gruppo Romano Laziale Mielodisplasie (GROM-L)","doi":"10.1016/j.leukres.2025.107703","DOIUrl":"10.1016/j.leukres.2025.107703","url":null,"abstract":"<div><div>Myelodysplastic syndromes/neoplasms (MDS) are a heterogeneous group of blood disorders characterized by distinctive biological and clinical features. Diagnosis typically relies on bone marrow examination and cytogenetic/molecular analysis. However, a small subset of patients lacks detectable cytogenetic or genetic abnormalities, making diagnosis challenging and reliant solely on marrow dysplasia and cytopenia. Here, we conducted a multicenter retrospective study investigating the clinical and hematological features of patients with MDS lacking detectable cytogenetic or molecular alterations. From a cohort of 329 MDS patients who underwent genetic testing at our laboratory of “Diagnostica Avanzata Oncoematologica”, we selected 62 patients presenting with unexplained cytopenia, suspected MDS, and a non-informative cytogenomic profile. Of these, 26 were ultimately diagnosed with alternative conditions such as aplastic anemia, drug/radiation toxicity, multiple myeloma, and others. The patients with non-informative genetic profile had a median age of 60 years and a female predominance (67 %). Autoimmune diseases (AD) were the most frequently observed comorbidities (26 %), and neutropenia was the most common type of cytopenia (56 %), followed by thrombocytopenia (22 %), and anemia (19 %). Most patients had bi-lineage or tri-lineage dysplasia, and had low-risk disease according to IPSS-R and IPSS-M. Only one patient progressed to AML at a median follow-up of 12 months (IQR for the test cohort: 2–25). MDS lacking classical myeloid clonal alteration represent a unique clinical-biological subtype whereby marrow assessment along with a thorough clinical workup is crucial.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"153 ","pages":"Article 107703"},"PeriodicalIF":2.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868221","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 impact of tyrosine kinases related mutations in NPM1 mutated acute myeloid leukaemia: A report from the Northern Italy Leukaemia Group (NILG) multicentre randomized trial 02/06","authors":"Gianluca Cavallaro ,&nbsp;Silvia Salmoiraghi ,&nbsp;Roberta Cavagna ,&nbsp;Chiara Pavoni ,&nbsp;Clara Belotti ,&nbsp;Martina Milani ,&nbsp;Elena Oldani ,&nbsp;Marco Frigeni ,&nbsp;Tamara Intermesoli ,&nbsp;Anna Grassi ,&nbsp;Renato Bassan ,&nbsp;Orietta Spinelli ,&nbsp;Alessandro Rambaldi ,&nbsp;Federico Lussana","doi":"10.1016/j.leukres.2025.107702","DOIUrl":"10.1016/j.leukres.2025.107702","url":null,"abstract":"<div><div>Co-mutational patterns play a role in the clinical outcome of nucleophosmin-1 (<em>NPM1</em>) mutated acute myeloid leukaemia (AML). Tyrosine kinase (TK) related gene mutations are included in these additional mutations, but their impact on prognosis of <em>NPM1</em>-mutated AML is unknown. We analyzed the outcomes of patients with <em>NPM1</em> AML with TK related mutations treated with intensive chemotherapy in the prospective randomized trial NILG AML 02/06, with regards to <em>NPM1-FLT3-ITD</em> and <em>NPM1</em>-isolated. Data show that additional TK related mutations do not impact the favorable prognosis on <em>NPM1-</em>mutated AML, unlike <em>NPM1-FLT3-ITD</em> mutated AML, for which consolidation with allogeneic stem cell transplantation should be considered for all young and fit patients in first complete remission.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"153 ","pages":"Article 107702"},"PeriodicalIF":2.1,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868329","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 I clinical trial of lenalidomide combined with bortezomib for acute myeloid leukemia or myelodysplastic syndrome relapsing after allogeneic stem cell transplantation","authors":"Brandon J. Aubrey ,&nbsp;Traci Blonquist ,&nbsp;Malgorzata McMasters ,&nbsp;Gabriela Hobbs ,&nbsp;Steven McAfee ,&nbsp;Jacalyn Rosenblatt ,&nbsp;Philip Amrein ,&nbsp;Christine Connolly ,&nbsp;Aura Ramos ,&nbsp;Emma Logan ,&nbsp;Bimalangshu Dey ,&nbsp;Thomas Spitzer ,&nbsp;David Avigan ,&nbsp;Yi-Bin Chen ,&nbsp;Karen Ballen ,&nbsp;Areej El-Jawahri ,&nbsp;Amir T. Fathi ,&nbsp;Andrew M. Brunner","doi":"10.1016/j.leukres.2025.107693","DOIUrl":"10.1016/j.leukres.2025.107693","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Allogeneic hematopoietic cell transplantation (HCT) may improve long-term survival in patients with MDS or AML but disease relapse following HCT is common, with limited subsequent treatment options and extremely poor post-relapse outcomes. Lenalidomide and bortezomib are therapies which, in this setting, may exert antiproliferative effects, enhance graft-vs-leukemia immune responses, and potentiate chemotherapeutic drugs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;We sought to evaluate the safety and preliminary efficacy of bortezomib in combination with high dose lenalidomide in patients with AML or MDS relapsing after HCT.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study design&lt;/h3&gt;&lt;div&gt;We conducted a phase I, dose-escalation, multi-center study of bortezomib added to high dose lenalidomide in patients with AML or MDS relapsing after HCT. We enrolled adult patients with recurrent or progressive AML or MDS after transplant; patients were required to be off systemic immunosuppression, with no evidence of GVHD, and with adequate organ function. Escalating doses of bortezomib were administered on days 2, 5, 9, and 12 of each cycle, while lenalidomide was given at 50 mg daily on days 1–21 of a 28-day cycle. DLTs were assessed during the first 2 cycles of induction and responses were assessed within this period. After achieving a treatment response, patients could proceed to maintenance dosing. The primary endpoint was toxicity and to establish the maximally tolerated dose (MTD) of the combination, while secondary endpoints included response rate and duration of responses.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;21 patients were enrolled, with a median age of 66 years (range 23–74). The majority of patients enrolled had AML (19/21). Three patients were enrolled at each bortezomib dose level of 0.7 mg/m&lt;sup&gt;2&lt;/sup&gt;, 1.0 mg/m&lt;sup&gt;2&lt;/sup&gt; and 1.3 mg/m&lt;sup&gt;2&lt;/sup&gt;. One patient experienced dose-limiting toxicity at 1.3 mg/m&lt;sup&gt;2&lt;/sup&gt; (received &lt;50 % doses) and the cohort was expanded to 6 total patients, establishing this as the recommended phase two dose (RP2D); a maximum tolerated dose (MTD) was not reached. An additional 9 expansion patients were treated at this dose level for a total of 15 patients treated with lenalidomide 50 mg and bortezomib 1.3 mg/m&lt;sup&gt;2&lt;/sup&gt;. During dose expansion, grade 4 toxicities attributed to study drug included grade 4 neutropenia (n = 5), thrombocytopenia (n = 3), and febrile neutropenia (n = 1). Across all cohorts (n = 21), 1 patient (4.8 %) achieved CR and 3 patients (14.3 %) achieved CRi (composite CR/CRi rate of 19 %). Of the 15 patients treated at the RP2D, 4 patients had progressive disease after the first induction cycle, and 2 patients stopped therapy during induction cycle 2. A total of 9 patients completed both induction cycles. Of the 15 patients treated at the RP2D, 1 achieved CR, 2 achieved CRi (composite CR/CRi 20 %, CI 5.7–44.0 %) and 4 patients had stable disease. Chimerism during treatment generally","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"153 ","pages":"Article 107693"},"PeriodicalIF":2.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843827","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":"Incidence and risk factors of venous thromboembolism in patients with acute Leukemia: A systematic review and meta-analysis","authors":"Wenxuan Zhang ,&nbsp;Yuanxin Cui ,&nbsp;Jiamao Wu ,&nbsp;Yuyan Chen ,&nbsp;Rui Wang ,&nbsp;Jingnan An ,&nbsp;Yujuan Zhang","doi":"10.1016/j.leukres.2025.107694","DOIUrl":"10.1016/j.leukres.2025.107694","url":null,"abstract":"<div><h3>Introduction</h3><div>Currently, no systematic review has been published regarding the incidence and risk factors of venous thromboembolism (VTE) in patients with acute leukemia. This study was implemented to identify the incidence and risk factors of VTE in patients with acute leukemia, aiming to offer guidance for corresponding clinical diagnosis and treatment.</div></div><div><h3>Materials and methods</h3><div>Studies in PubMed, Cochrane Library, Embase, and Web of Science were fully searched from database to January 2024. The risk of bias was assessed using NOS scale. Data analysis was performed with STATA 15.1.</div></div><div><h3>Results</h3><div>Twenty-two studies covering 53,433 samples were included. The overall incidence of VTE in patients with acute leukemia was 9 % (95 % CI: 0.07–0.12; <em>P</em> &lt; 0.01). Older age in children (OR=2.21; 95 % CI: 1.40–3.49; <em>P</em> &lt; 0.001), older age in adults (OR=2.05; 95 % CI: 1.02–4.10; <em>P</em> = 0.044), non-B cell subtype in acute lymphoblastic leukemia (ALL) (OR=1.85; 95 % CI: 1.43–2.39; <em>P</em> &lt; 0.001) were risk factors for VTE in patients with acute leukemia, while Hispanic ethnicity was associated with a lower risk of VTE (OR=0.81; 95 % CI: 0.67–0.99; <em>P</em> = 0.040). Subgroup analysis results revealed that, in patients with acute myeloid leukemia, male gender was associated with a lower risk of VTE (OR=0.83; 95 % CI: 0.70–0.99; <em>P</em> = 0.039); in patients with ALL, older age in adults (OR=4.41; 95 % CI: 2.25–8.66; <em>P</em> &lt; 0.001) and T-cell subtype (OR=1.82; 95 % CI: 1.39–2.37; <em>P</em> &lt; 0.001) was a risk factor, non-White was associated with a lower risk of VTE (OR=0.69; 95 % CI: 0.54–0.89; <em>P</em> = 0.004).</div></div><div><h3>Conclusion</h3><div>The overall incidence of VTE was high in patients with acute leukemia. Older age and T-cell phenotype were risk factors, while Hispanic ethnicity was associated with a lower risk of VTE. This suggests more attention should be paid to high-risk groups in clinical practice.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"153 ","pages":"Article 107694"},"PeriodicalIF":2.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843826","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":"Safety and efficacy of the combination of azacitidine with venetoclax after hypomethylating agent failure in higher-risk myelodysplastic syndrome","authors":"Julie S. Braish ,&nbsp;Guillermo Montalban-Bravo ,&nbsp;Farhad Ravandi ,&nbsp;Nicholas Short ,&nbsp;Tapan Kadia ,&nbsp;Maro Ohanian ,&nbsp;Kelly Chien ,&nbsp;Lucia Masarova ,&nbsp;Koji Sasaki ,&nbsp;Musa Yilmaz ,&nbsp;Sanam Logahvi ,&nbsp;Naval Daver ,&nbsp;Gautam Borthakur ,&nbsp;Elias Jabbour ,&nbsp;Heather Schneider ,&nbsp;Lizabeth T. Romero ,&nbsp;Hagop Kantarjian ,&nbsp;Guillermo Garcia-Manero","doi":"10.1016/j.leukres.2025.107692","DOIUrl":"10.1016/j.leukres.2025.107692","url":null,"abstract":"<div><h3>Objective</h3><div>Therapies for patients with higher-risk myelodysplastic syndromes (HR-MDS) who have failed hypomethylating agents (HMAs) are needed. This Phase I/II study evaluates the safety, tolerability, and efficacy of venetoclax, an orally bioavailable BCL-2 inhibitor, in combination with azacitidine in this population.</div></div><div><h3>Methods</h3><div>We conducted a single-center, dose-escalation, Phase I/II trial (NCT04550442) involving 33 patients with HR-MDS or CMML (IPSS ≥ 1.5) who had progressed after prior HMA therapy. Patients received intravenous or subcutaneous azacitidine (SC) (75 mg/m² for 5 days) and venetoclax (100–400 mg for 7–14 days in a 28-day cycle). The primary endpoints were safety/tolerability (Phase 1) and overall response rate (ORR) (Phase 2).</div></div><div><h3>Results</h3><div>Patients received a median of 3 cycles (range, 1–22). The maximum tolerated dose of venetoclax was 400 mg. Common grade 3–4 adverse events included neutropenia (19 %) and thrombocytopenia (10 %). The 4-week early mortality rate was 9 %. The ORR was 49 %, and the median overall survival (OS) was 7 months (95 % CI, 3.5–10.5). The median progression-free survival (PFS) was 6 months (95 % CI, 3.0–9.0). Four patients (12 %) underwent stem cell transplantation, with 3 of 4 alive at last follow-up (75 %).</div></div><div><h3>Conclusion</h3><div>Combining venetoclax with azacitidine is feasible for HR-MDS and CMML patients who failed prior HMA therapy. However, this combination did not significantly improve clinical outcomes in this patient population.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"153 ","pages":"Article 107692"},"PeriodicalIF":2.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847763","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 of ZNF384 as a regulator of epigenome in leukemia","authors":"Laura C. Zárraga Vargas ,&nbsp;Julio Ortíz-Ortíz ,&nbsp;Yamelie A. Martínez ,&nbsp;Gabriela E. Campos Viguri ,&nbsp;Francisco I. Torres Rojas ,&nbsp;Pedro A. Ávila-López","doi":"10.1016/j.leukres.2025.107691","DOIUrl":"10.1016/j.leukres.2025.107691","url":null,"abstract":"<div><div>Leukemia is a complex hematologic cancer driven by genetic and epigenetic changes that impact gene expression. Understanding these molecular mechanisms is essential for improving leukemia diagnosis and prognosis. This study examines the role of the zinc finger protein ZNF384 in the epigenome and its influence on gene regulation in leukemia. We analyzed next-generation sequencing data from The Encyclopedia of DNA Elements (ENCODE), integrating datasets such as chromatin immunoprecipitation sequencing (ChIP-seq) of ZNF384 and regulatory histone marks, RNA sequencing (RNA-seq), and Hi-C data from K562 and GM12878 cells. Additionally, we used RNA-seq from K562 ZNF384 knock-down (KD) cells generated via CRISPR interference (CRISPRi) to validate our findings. This enabled us to explore the chromatin interaction patterns of ZNF384 and its regulatory impact. Our results demonstrate that ZNF384 associates with promoters and enhancers in K562 and GM12878 cells, facilitating increased transcription levels. We also found ZNF384 enriched at topologically associating domain (TAD) boundaries and chromatin loops, suggesting a role in three-dimensional (3D) chromatin organization. Furthermore, we identified a significant binding of ZNF384 at SINE-Alu elements in both K562 and GM12878 cells. In summary, this study highlights the regulatory role of ZNF384 in the leukemia epigenome and its impact on gene expression. Understanding the oncogenic implications of ZNF384 may improve leukemia diagnosis and prognosis.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"153 ","pages":"Article 107691"},"PeriodicalIF":2.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843904","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 applicability of the ELN2020 criteria for tyrosine kinase inhibitor discontinuation in chronic myeloid leukemia: insights from a multicenter retrospective study in real-world practice","authors":"Yuto Hibino ,&nbsp;Shin Fujisawa ,&nbsp;Katsumichi Fujimaki ,&nbsp;Maki Hagihara ,&nbsp;Hiroyuki Fujita ,&nbsp;Masatsugu Tanaka ,&nbsp;Kosuke Takayama ,&nbsp;Takaaki Takeda ,&nbsp;Ayako Matsumura ,&nbsp;Taisei Suzuki ,&nbsp;Yoshimi Ishii ,&nbsp;Yuki Nakajima ,&nbsp;Takuya Miyazaki ,&nbsp;Hideaki Nakajima","doi":"10.1016/j.leukres.2025.107689","DOIUrl":"10.1016/j.leukres.2025.107689","url":null,"abstract":"<div><div>The prognosis of chronic myeloid leukemia has significantly improved with the introduction of tyrosine kinase inhibitors (TKIs). However, indefinite TKI treatment can lead to adverse effects and high costs. Recent studies have suggested that treatment-free remission (TFR) is achievable in patients with a deep molecular response (DMR). The present multicenter, retrospective observational study conducted in Japan evaluated the applicability of the European LeukemiaNet (ELN) 2020 TKI discontinuation criteria, which recommend TKI therapy of ≥ 5 years with sustained MR⁴ for ≥ 3 years or MR^4.5 for ≥ 2 years. A total of 100 patients who discontinued TKI therapy were analyzed, with 70 meeting the ELN2020 criteria. The overall 12-month TFR rate was 71.9 %. Univariate analysis showed that both the duration of DMR and TKI therapy were significantly associated with TFR, with hazard ratios (HR) of 0.305 and 0.450, respectively. Only DMR duration remained significant (HR 0.362) in multivariate analysis. Patients who lost MMR after TKI discontinuation rapidly re-achieved molecular response upon TKI resumption. The most common reason for TKI discontinuation was elective cessation, followed by adverse events, among which pleural effusion due to dasatinib was the most frequent. The results of this study, the first to assess the ELN2020 criteria in a Japanese cohort, suggest that the criteria are applicable in real-world clinical practice.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"152 ","pages":"Article 107689"},"PeriodicalIF":2.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799877","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":"Safety, tolerability, and pharmacokinetics of ASP1235 in relapsed or refractory acute myeloid leukemia: A phase 1 study","authors":"Monzr M. Al Malki ,&nbsp;Mark D. Minden ,&nbsp;Elizabeth Shima Rich ,&nbsp;Jason E. Hill ,&nbsp;Stanley C. Gill ,&nbsp;Alan Fan ,&nbsp;Christine E. Fredericks ,&nbsp;Amir T. Fathi ,&nbsp;Maher Abdul-Hay","doi":"10.1016/j.leukres.2025.107690","DOIUrl":"10.1016/j.leukres.2025.107690","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is an aggressive hematologic malignancy. Although new agents including targeted therapies for relapsed or refractory (R/R) AML have been introduced, poor outcomes remain, requiring the need for novel approaches. One novel approach is the use of antibody-drug conjugates (ADCs). We conducted an early phase clinical trial with ASP1235, an ADC targeting FMS-like tyrosine kinase 3. In total, 43 patients with R/R AML were treated with ASP1235. The most common adverse events (AEs) included elevated liver transaminase levels, ocular toxicity, and muscular weakness. Ocular treatment-emergent AEs (TEAEs) were observed in 53 % of patients; most were mild or moderate in severity. The most common ocular TEAEs were blurred vision, dry eye, keratitis, photophobia, and reduced visual acuity. Serious (grade ≥3) ocular TEAEs occurred in 16.3 % of patients, with only 1 patient experiencing grade 4 keratitis. Six patients achieved composite complete remission (complete remission [CR] + CR with incomplete hematologic recovery + CR with incomplete platelet recovery), 2 of whom proceeded to hematopoietic cell transplantation with long-term leukemia-free survival. This trial was registered at <span><span>www.clinicaltrials.gov</span><svg><path></path></svg></span> as #NCT02864290.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"152 ","pages":"Article 107690"},"PeriodicalIF":2.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to venetoclax in patients with blastic plasmacytoid dendritic cell neoplasm","authors":"Kirsty M Sharplin,&nbsp;Catherine Vassiliou,&nbsp;James Nguyen,&nbsp;Bryone J. Kuss,&nbsp;Stephen B Ting,&nbsp;Hilda Mangos,&nbsp;Hamish Scott,&nbsp;Anna Brown,&nbsp;Piers Blombery,&nbsp;Andrew Wei,&nbsp;David M. Ross","doi":"10.1016/j.leukres.2025.107678","DOIUrl":"10.1016/j.leukres.2025.107678","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"152 ","pages":"Article 107678"},"PeriodicalIF":2.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784013","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":"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}