Pub Date : 2026-02-02DOI: 10.1038/s41375-025-02843-9
David Kealy, Ruth Ellerington, Suraj Bansal, Jessie J. F. Medeiros, Catherine A. Hawley, Andy G. X. Zeng, Jakub Lukaszonek, Katie A. West, Aparna D. Sinha, Gillian Caalim, Richard T. Gawne, Jacob Pope, Bianca Lima Ferreira, Nicole-Mae Blacknell, Bryce Drylie, Jenny Chatzigerou, Hwei Minn Khoo, Adam C. Wilkinson, Adele K. Fielding, Guanlin Wang, Bethan Psaila, David G. Kent, Ian S. Hitchcock, Andrew N. Holding, Andrew S. Mason, Vikas Gupta, John E. Dick, Katherine S. Bridge
Hypoxia-inducible factors (HIFs) are master transcriptional regulators, central to cellular survival in hypoxia and frequently activated within malignancy. Whilst malignant context directs the role of HIFs within oncogenesis, these mechanisms are not well characterised. Applying the JAK2V617F myeloproliferative neoplasms (MPNs) oncogene-driver model, in which HIF-1α is stabilised in normoxia (20% O2), we sought to determine whether the modality of HIF-1 activation directs its function. Through direct analysis of hypoxia-activated vs. JAK2V617F-activated HIF-1 at the chromatin, we define a JAK2V617F-HIF-1 regulon that diverges from canonical HIF/hypoxia targets. In a cohort of 172 JAK2V617F-MPN patients, we observe significant association of the JAK2V617F-HIF-1 regulon, but not canonical HIF-1 gene signatures, with disease severity, progression, and patient survival. We further define a subset gene signature (HIF1-MPN-BP) significantly associated with spontaneous transformation to blast phase MPNs. Finally, we identify that JAK2V617F-induced HIF-1α stabilisation is mediated via PIM1 kinase. Our findings demonstrate that HIF-1 activation by the JAK2V617F-PIM1 axis significantly alters HIF-1 transcription function, desensitising HIF-1 activity to cellular oxygen levels, and restricting the HIF-1 regulon to a set of disease-associated target genes within JAK2V617F-MPNs. These findings restore the potential for specific therapeutic targeting of HIF-1 by delineating malignant activation from the physiological hypoxic response.
{"title":"JAK2V617F reprograms Hypoxia Inducible Factor-1 to induce a non-canonical hypoxia regulon in myeloproliferative neoplasms","authors":"David Kealy, Ruth Ellerington, Suraj Bansal, Jessie J. F. Medeiros, Catherine A. Hawley, Andy G. X. Zeng, Jakub Lukaszonek, Katie A. West, Aparna D. Sinha, Gillian Caalim, Richard T. Gawne, Jacob Pope, Bianca Lima Ferreira, Nicole-Mae Blacknell, Bryce Drylie, Jenny Chatzigerou, Hwei Minn Khoo, Adam C. Wilkinson, Adele K. Fielding, Guanlin Wang, Bethan Psaila, David G. Kent, Ian S. Hitchcock, Andrew N. Holding, Andrew S. Mason, Vikas Gupta, John E. Dick, Katherine S. Bridge","doi":"10.1038/s41375-025-02843-9","DOIUrl":"https://doi.org/10.1038/s41375-025-02843-9","url":null,"abstract":"Hypoxia-inducible factors (HIFs) are master transcriptional regulators, central to cellular survival in hypoxia and frequently activated within malignancy. Whilst malignant context directs the role of HIFs within oncogenesis, these mechanisms are not well characterised. Applying the JAK2V617F myeloproliferative neoplasms (MPNs) oncogene-driver model, in which HIF-1α is stabilised in normoxia (20% O2), we sought to determine whether the modality of HIF-1 activation directs its function. Through direct analysis of hypoxia-activated vs. JAK2V617F-activated HIF-1 at the chromatin, we define a JAK2V617F-HIF-1 regulon that diverges from canonical HIF/hypoxia targets. In a cohort of 172 JAK2V617F-MPN patients, we observe significant association of the JAK2V617F-HIF-1 regulon, but not canonical HIF-1 gene signatures, with disease severity, progression, and patient survival. We further define a subset gene signature (HIF1-MPN-BP) significantly associated with spontaneous transformation to blast phase MPNs. Finally, we identify that JAK2V617F-induced HIF-1α stabilisation is mediated via PIM1 kinase. Our findings demonstrate that HIF-1 activation by the JAK2V617F-PIM1 axis significantly alters HIF-1 transcription function, desensitising HIF-1 activity to cellular oxygen levels, and restricting the HIF-1 regulon to a set of disease-associated target genes within JAK2V617F-MPNs. These findings restore the potential for specific therapeutic targeting of HIF-1 by delineating malignant activation from the physiological hypoxic response.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"14 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-29DOI: 10.1038/s41375-026-02864-y
Junren Chen,Robert Peter Gale
{"title":"Physician-complementing artificial intelligence in haematology: ushering in a new era.","authors":"Junren Chen,Robert Peter Gale","doi":"10.1038/s41375-026-02864-y","DOIUrl":"https://doi.org/10.1038/s41375-026-02864-y","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"14 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-26DOI: 10.1038/s41375-025-02849-3
Claus-Moritz Gräf, Moritz Reese, Angela Vicente-Luque, Nicolas Mönig, Charlotte Bruzeau, Ferran Nadeu, Maria Latacz, Johanna Bihler, Jörn Meinel, Maria Cartolano, Martin Peifer, Sílvia Beà, Elias Campo, Melanie Thelen, Paul J. Bröckelmann, Ron D. Jachimowicz
{"title":"Establishment and characterization of a CCND1-rearranged non-mantle cell lymphoma cell line and patient-derived xenograft model","authors":"Claus-Moritz Gräf, Moritz Reese, Angela Vicente-Luque, Nicolas Mönig, Charlotte Bruzeau, Ferran Nadeu, Maria Latacz, Johanna Bihler, Jörn Meinel, Maria Cartolano, Martin Peifer, Sílvia Beà, Elias Campo, Melanie Thelen, Paul J. Bröckelmann, Ron D. Jachimowicz","doi":"10.1038/s41375-025-02849-3","DOIUrl":"https://doi.org/10.1038/s41375-025-02849-3","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"41 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1038/s41375-025-02852-8
Vivian G Oehler,Olga Sala-Torra,Neta Gilderman,Lan Beppu,David W Woolston,Priscilla Namaganda,Jennifer Rynning,Inés García González,Andrea Towlerton,Jenna Voutsinas,Qian Wu,Cecilia C S Yeung,Jerald P Radich
The goal of the "Spot On CML" program is to provide diagnostic and monitoring tests to chronic myeloid leukemia (CML) patients in low- and middle-income countries (LMICs). Previously, we demonstrated reproducible BCR::ABL1 transcript quantification using dried blood spots (DBS). We have now optimized methods of DNA and RNA extraction from DBS, allowing the detection of myeloid gene variants, including ABL1 tyrosine kinase domain mutations. Among 177 CML patients from nine countries, ABL1 mutations were identified in 61 (34%) patients, with multiple mutations present in some cases. The most common ABL1 mutation was T315I (45.9% of patients with ABL1 mutations). Among 69 patients, 89 Tier I-II variants (pathogenic or likely pathogenic) were identified in other genes, including 52 ASXL1 variants in 49 patients. The detection of ASXL1 variants correlated strongly with the presence of ABL1 mutations (P = 3.51E-04). These methodologies are directly applicable to all assays used for the diagnosis, prognosis, and monitoring of CML and have important implications in bringing state-of-the-art genetic analysis to CML patients in LMICs.
{"title":"Next-generation sequencing from chronic myeloid leukemia dried blood spots: insights and implications for global oncology.","authors":"Vivian G Oehler,Olga Sala-Torra,Neta Gilderman,Lan Beppu,David W Woolston,Priscilla Namaganda,Jennifer Rynning,Inés García González,Andrea Towlerton,Jenna Voutsinas,Qian Wu,Cecilia C S Yeung,Jerald P Radich","doi":"10.1038/s41375-025-02852-8","DOIUrl":"https://doi.org/10.1038/s41375-025-02852-8","url":null,"abstract":"The goal of the \"Spot On CML\" program is to provide diagnostic and monitoring tests to chronic myeloid leukemia (CML) patients in low- and middle-income countries (LMICs). Previously, we demonstrated reproducible BCR::ABL1 transcript quantification using dried blood spots (DBS). We have now optimized methods of DNA and RNA extraction from DBS, allowing the detection of myeloid gene variants, including ABL1 tyrosine kinase domain mutations. Among 177 CML patients from nine countries, ABL1 mutations were identified in 61 (34%) patients, with multiple mutations present in some cases. The most common ABL1 mutation was T315I (45.9% of patients with ABL1 mutations). Among 69 patients, 89 Tier I-II variants (pathogenic or likely pathogenic) were identified in other genes, including 52 ASXL1 variants in 49 patients. The detection of ASXL1 variants correlated strongly with the presence of ABL1 mutations (P = 3.51E-04). These methodologies are directly applicable to all assays used for the diagnosis, prognosis, and monitoring of CML and have important implications in bringing state-of-the-art genetic analysis to CML patients in LMICs.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"50 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-22DOI: 10.1038/s41375-025-02855-5
Michela Ansuinelli, Nadia Peragine, Maria Stefania De Propris, Maria Cristina Puzzolo, Mariangela Di Trani, Loredana Elia, Cristina Skert, Roberto Cairoli, Simona Sica, Alessandro Rambaldi, Alessandra Tucci, Marco Cerrano, Daniele Vallisa, Valeria Cardinali, Antonino Mulè, Sabina Chiaretti, Anna Guarini, Robin Foà
In Ph+ acute lymphoblastic leukemia, frontline dasatinib plus blinatumomab (dasa+blina) is associated with long-term survival rates of 75-80%. The phase III GIMEMA ALL2820 trial has explored ponatinib with blinatumomab (pona+blina). In the present study, the immune modulation induced by dasa+blina and pona+blina was investigated. Immune cells were analyzed at the end of induction (T0) and after 2, 4 and 5 blinatumomab cycles (T2, T4, T5). Among 153 patients (43 dasa+blina, 110 pona+blina), the dasa+blina combination induced a significantly greater lymphocyte increase at T4 and T5 compared to pona+blina. The Treg counts decreased only in the dasa+blina treated patients. NK and NK-T cells increased significantly in the dasa+blina group, at all timepoints. Complete molecular responders (CMR) after dasatinib induction had significantly higher lymphocytes, T and NK cells compared to non-CMR patients. Bone marrow analyses showed higher activation (CD25, CD69) and lower exhaustion (PD1, TIM3) markers on NK and NK-T cells in dasa+blina treated patients. Dasa+blina patients exhibited a significantly enhanced NK cell capacity compared to ponatinib treated patients. Patients remaining on dasatinib maintained elevated NK cells with a more mature phenotype, suggesting a durable effect. These results highlight the greater dasa+blina immune activation, supporting a potential synergistic effect of the drug combination.
{"title":"Immunomodulatory effect of dasatinib plus blinatumomab versus ponatinib plus blinatumomab in newly diagnosed Ph+ acute lymphoblastic leukemia.","authors":"Michela Ansuinelli, Nadia Peragine, Maria Stefania De Propris, Maria Cristina Puzzolo, Mariangela Di Trani, Loredana Elia, Cristina Skert, Roberto Cairoli, Simona Sica, Alessandro Rambaldi, Alessandra Tucci, Marco Cerrano, Daniele Vallisa, Valeria Cardinali, Antonino Mulè, Sabina Chiaretti, Anna Guarini, Robin Foà","doi":"10.1038/s41375-025-02855-5","DOIUrl":"https://doi.org/10.1038/s41375-025-02855-5","url":null,"abstract":"<p><p>In Ph+ acute lymphoblastic leukemia, frontline dasatinib plus blinatumomab (dasa+blina) is associated with long-term survival rates of 75-80%. The phase III GIMEMA ALL2820 trial has explored ponatinib with blinatumomab (pona+blina). In the present study, the immune modulation induced by dasa+blina and pona+blina was investigated. Immune cells were analyzed at the end of induction (T0) and after 2, 4 and 5 blinatumomab cycles (T2, T4, T5). Among 153 patients (43 dasa+blina, 110 pona+blina), the dasa+blina combination induced a significantly greater lymphocyte increase at T4 and T5 compared to pona+blina. The Treg counts decreased only in the dasa+blina treated patients. NK and NK-T cells increased significantly in the dasa+blina group, at all timepoints. Complete molecular responders (CMR) after dasatinib induction had significantly higher lymphocytes, T and NK cells compared to non-CMR patients. Bone marrow analyses showed higher activation (CD25, CD69) and lower exhaustion (PD1, TIM3) markers on NK and NK-T cells in dasa+blina treated patients. Dasa+blina patients exhibited a significantly enhanced NK cell capacity compared to ponatinib treated patients. Patients remaining on dasatinib maintained elevated NK cells with a more mature phenotype, suggesting a durable effect. These results highlight the greater dasa+blina immune activation, supporting a potential synergistic effect of the drug combination.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-22DOI: 10.1038/s41375-026-02860-2
Giovanni Barosi,Annalisa De Silvestri,Robert Peter Gale,Vittorio Rosti
{"title":"Prognostic value of anemia plus thrombocytopenia in primary myelofibrosis.","authors":"Giovanni Barosi,Annalisa De Silvestri,Robert Peter Gale,Vittorio Rosti","doi":"10.1038/s41375-026-02860-2","DOIUrl":"https://doi.org/10.1038/s41375-026-02860-2","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"263 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MYB is a master transcription factor for the hematopoietic system, and its dysregulation drives the development and therapy resistance of leukemia. However, the mechanisms of MYB regulation and MYB-related therapy resistance are still unclear. Here, we identified two bidirectional enhancer RNAs (eRNAs), MY34UE-AS and MY34UE-S, transcribed from the -34 kb enhancer region of MYB. Both eRNAs promote MYB transcription, proliferation, and migration in human leukemia cells, although through different MYB promoters. MY34UE-AS physically interacts with PURB that binds near MYB TSS2, promoting long-range looping between downstream -34 kb enhancer elements and TSS2, ultimately activating TSS2. While MY34UE-S facilitates DNA looping between upstream -34 kb enhancer elements and TSS1, promoting TSS1 transcription. TSS2, but not TSS1, activity increases in drug resistant leukemia cells, resulting increased expression of N-terminally truncated MYB (ΔN MYB) when total MYB remains unaltered. Compared to full-length MYB, ΔN MYB more potently promotes drug resistance through FTH1 and EZH2 pathway, and targeting MY34UE-AS more efficiently alleviates drug resistance than targeting MY34UE-S. The above relationship of MY34UE-AS/MY34UE-S, TSS2/TSS1, and prognosis was also verified in clinical leukemia samples. For the first time we provide the mechanisms underlying promoter usage of MYB and MYB TSS2 mediated drug resistance in human leukemia.
{"title":"Distal enhancer RNAs regulate alternative promoter usage of MYB and drug resistance in human leukemia cells.","authors":"Yucheng Wang,Xiang Wang,Mengjia Li,Hongkuan Song,Chao Liu,Mengjie Shi,Xiaoxiao Tao,Siyu Shen,Xinyu Li,Huiying Fang,Zhenhua Zhou,Junfang Zhang,Bingshe Han","doi":"10.1038/s41375-026-02862-0","DOIUrl":"https://doi.org/10.1038/s41375-026-02862-0","url":null,"abstract":"MYB is a master transcription factor for the hematopoietic system, and its dysregulation drives the development and therapy resistance of leukemia. However, the mechanisms of MYB regulation and MYB-related therapy resistance are still unclear. Here, we identified two bidirectional enhancer RNAs (eRNAs), MY34UE-AS and MY34UE-S, transcribed from the -34 kb enhancer region of MYB. Both eRNAs promote MYB transcription, proliferation, and migration in human leukemia cells, although through different MYB promoters. MY34UE-AS physically interacts with PURB that binds near MYB TSS2, promoting long-range looping between downstream -34 kb enhancer elements and TSS2, ultimately activating TSS2. While MY34UE-S facilitates DNA looping between upstream -34 kb enhancer elements and TSS1, promoting TSS1 transcription. TSS2, but not TSS1, activity increases in drug resistant leukemia cells, resulting increased expression of N-terminally truncated MYB (ΔN MYB) when total MYB remains unaltered. Compared to full-length MYB, ΔN MYB more potently promotes drug resistance through FTH1 and EZH2 pathway, and targeting MY34UE-AS more efficiently alleviates drug resistance than targeting MY34UE-S. The above relationship of MY34UE-AS/MY34UE-S, TSS2/TSS1, and prognosis was also verified in clinical leukemia samples. For the first time we provide the mechanisms underlying promoter usage of MYB and MYB TSS2 mediated drug resistance in human leukemia.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"95 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-19DOI: 10.1038/s41375-025-02847-5
Delphine Rea, Slawomira Kyrcz-Krzemien, Paolo Sportoletti, Jiří Mayer, Arpad Illes, Anna Angona Figueras, Alexander Kiani, Aude Charbonnier, Theodoros Marinakis, Leif Stenke, Juan Luis Steegmann, Giuseppe Saglio, Andrzej Hellmann, Dietger Niederwieser, Peter Schuld, Gianantonio Rosti
The phase 3 ENESTPath study investigated treatment-free remission (TFR) rates in patients with chronic Philadelphia chromosome-positive (Ph+) and/or BCR::ABL1+ chronic myeloid leukemia who had not achieved deep molecular response (DMR) after >2 years of imatinib treatment and were switched to nilotinib 300 mg twice daily (BID). After 24 months of treatment, patients with a stable DMR were randomized to either enter the TFR phase (Arm 1) or continue nilotinib consolidation for an additional 12 months and then enter the TFR phase if in stable DMR (Arm 2). The primary endpoint was the proportion of patients who remained in TFR (≥MR4.0 [BCR::ABL1IS ≤ 0.01%]) without molecular relapse at the end of 12 months. Of the 620 patients enrolled, 239 (38.5%) achieved stable MR4.0 and were randomized to Arm 1 (n = 120) or Arm 2 (n = 119). In the TFR phase, MR4.0 rates at 12 months (Arm 1: 31.9%, Arm 2: 37.5%; p = 0.383) and 24 months (Arm 1: 29.4%, Arm 2: 30.8%) revealed no differences in TFR success between 2 and 3 years of nilotinib. Irrespective of the consolidation duration, switching to nilotinib 300 mg BID provided the opportunity to achieve TFR if patients were unable to reach stable DMR with first-line imatinib.
{"title":"Treatment-free remission after two nilotinib consolidation durations in chronic myeloid leukemia treated with imatinib: Phase 3 ENESTPath results.","authors":"Delphine Rea, Slawomira Kyrcz-Krzemien, Paolo Sportoletti, Jiří Mayer, Arpad Illes, Anna Angona Figueras, Alexander Kiani, Aude Charbonnier, Theodoros Marinakis, Leif Stenke, Juan Luis Steegmann, Giuseppe Saglio, Andrzej Hellmann, Dietger Niederwieser, Peter Schuld, Gianantonio Rosti","doi":"10.1038/s41375-025-02847-5","DOIUrl":"https://doi.org/10.1038/s41375-025-02847-5","url":null,"abstract":"<p><p>The phase 3 ENESTPath study investigated treatment-free remission (TFR) rates in patients with chronic Philadelphia chromosome-positive (Ph+) and/or BCR::ABL1<sup>+</sup> chronic myeloid leukemia who had not achieved deep molecular response (DMR) after >2 years of imatinib treatment and were switched to nilotinib 300 mg twice daily (BID). After 24 months of treatment, patients with a stable DMR were randomized to either enter the TFR phase (Arm 1) or continue nilotinib consolidation for an additional 12 months and then enter the TFR phase if in stable DMR (Arm 2). The primary endpoint was the proportion of patients who remained in TFR (≥MR<sup>4.0</sup> [BCR::ABL1<sup>IS</sup> ≤ 0.01%]) without molecular relapse at the end of 12 months. Of the 620 patients enrolled, 239 (38.5%) achieved stable MR<sup>4.0</sup> and were randomized to Arm 1 (n = 120) or Arm 2 (n = 119). In the TFR phase, MR<sup>4.0</sup> rates at 12 months (Arm 1: 31.9%, Arm 2: 37.5%; p = 0.383) and 24 months (Arm 1: 29.4%, Arm 2: 30.8%) revealed no differences in TFR success between 2 and 3 years of nilotinib. Irrespective of the consolidation duration, switching to nilotinib 300 mg BID provided the opportunity to achieve TFR if patients were unable to reach stable DMR with first-line imatinib.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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