Myeloproliferative neoplasms with concomitant chronic myeloid leukemia are associated with TKI resistance and poor outcomes

Chronic myeloid leukemia (CML) and Philadelphia (Ph)-negative myeloproliferative neoplasms (MPN) are generally distinct clonal disorders, with the co-occurrence of BCR::ABL1 rearrangement with concomitant Ph-negative MPN rarely reported. Here we describe the largest known international cohort of Ph-negative MPN and coexisting CML providing important insights into this rare clinical scenario. We performed an international, multicenter, retrospective analysis of patients with concomitant BCR::ABL1 rearrangement and Ph-negative MPN, identifying 61 cases from 30 centers in 7 countries, over a 29-year period (1996-2025). Thirty-one patients (50.8%) had Ph-negative MPN preceding CML, 18 patients (29.5%) had CML preceding Ph-negative MPN, and 12 patients (19.7%) had Ph-negative MPN and CML diagnosed simultaneously. We observed increased TKI resistance and myelofibrotic transformation, especially in patients initially diagnosed with Ph-negative MPN. In this group, 35.4% (n = 11) progressed to MF, 2 patients to blast-phase MPN, and 69.2% (n = 18) failed to achieve a complete cytogenetic response. The rare e1a2 BCR::ABL1 transcript was notably prevalent which is associated with TKI resistance and a more aggressive disease course in CML. We described superior survival in those with Ph-negative MPN preceding CML, with median OS not reached, compared with 277 months for CML preceding Ph-negative MPN and 100 months for those diagnosed simultaneously (p = 0.05).

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Journal
Leukemia
Published
2026-03-27
DOI
https://doi.org/10.1038/s41375-026-02928-z
Primary Topic
Chronic Myeloid Leukemia Treatments
Type
article
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article

Myeloproliferative neoplasms with concomitant chronic myeloid leukemia are associated with TKI resistance and poor outcomes

P. Cervi, Yasmin Reyal, Dominik Chraniuk, Tom Taylor et al.
Leukemia
Chronic Myeloid Leukemia Treatments
article

Myeloproliferative neoplasms with concomitant chronic myeloid leukemia are associated with TKI resistance and poor outcomes

P. Cervi, Yasmin Reyal, Dominik Chraniuk, Tom Taylor, Siamak Arami, Anna L. Godfrey, Srinivasan Narayanan, Marta Sobas, Helen Bentley, Mikhail Fominykh, Lyne Gagnon, Jarosław Piszcz, J Pavlu, Rebecca Frewin, Hugues de Lavallade, Jenny Byrne, Patryk Sobieralski, Annalisa Condorelli, Mansour Ceesay, Kawai Yip, Lee-Yung Shih, Franck-Emmanuel Nicolini, Andres Virchis, Thomas Cummin, Julie Hildt, Clémence Santana, A J Mead, Robert Delage, Alero Ajayi, Krzysztof Lewandowski, Guy Hannah, Weronika Lebowa, Andrea Duminuco, Ashlyn Chee, Deborah Rahman, Deepti H. Radia, Claire Harrison, Dragana Milojkovic, Fabio Stagno, Patrick Harrington
article en

Abstract

Chronic myeloid leukemia (CML) and Philadelphia (Ph)-negative myeloproliferative neoplasms (MPN) are generally distinct clonal disorders, with the co-occurrence of BCR::ABL1 rearrangement with concomitant Ph-negative MPN rarely reported. Here we describe the largest known international cohort of Ph-negative MPN and coexisting CML providing important insights into this rare clinical scenario. We performed an international, multicenter, retrospective analysis of patients with concomitant BCR::ABL1 rearrangement and Ph-negative MPN, identifying 61 cases from 30 centers in 7 countries, over a 29-year period (1996-2025). Thirty-one patients (50.8%) had Ph-negative MPN preceding CML, 18 patients (29.5%) had CML preceding Ph-negative MPN, and 12 patients (19.7%) had Ph-negative MPN and CML diagnosed simultaneously. We observed increased TKI resistance and myelofibrotic transformation, especially in patients initially diagnosed with Ph-negative MPN. In this group, 35.4% (n = 11) progressed to MF, 2 patients to blast-phase MPN, and 69.2% (n = 18) failed to achieve a complete cytogenetic response. The rare e1a2 BCR::ABL1 transcript was notably prevalent which is associated with TKI resistance and a more aggressive disease course in CML. We described superior survival in those with Ph-negative MPN preceding CML, with median OS not reached, compared with 277 months for CML preceding Ph-negative MPN and 100 months for those diagnosed simultaneously (p = 0.05).

Leukemia
University of Messina (IT), Poznan University of Medical Sciences (PL), Jagiellonian University (PL), Nottingham University Hospitals NHS Trust (GB), University College London Hospitals NHS Foundation Trust (GB), Medical University of Białystok (PL), Imperial College Healthcare NHS Trust (GB), Medical University of Silesia (PL), Royal Free London NHS Foundation Trust (GB), Chang Gung University (TW), King's College London (GB), Guy's and St Thomas' NHS Foundation Trust (GB), Southend University Hospital NHS Foundation Trust (GB), London North West Healthcare NHS Trust (GB), South Essex Partnership University Foundation NHS Trust (GB), Churchill Hospital (GB), St George’s University Hospitals NHS Foundation Trust (GB), Hammersmith Hospital (GB), Gloucestershire Hospitals NHS Foundation Trust (GB), Cambridge University Hospitals NHS Foundation Trust (GB), University Hospital Southampton NHS Foundation Trust (GB), Nicolaus Copernicus University (PL), Chang Gung Memorial Hospital (TW), South London Healthcare NHS Trust (GB), Portsmouth Hospitals NHS Trust (GB), Ospedale Papa Giovanni XXIII (IT), MRC Weatherall Institute of Molecular Medicine (GB), Mid Essex Hospital Services NHS Trust (GB), Dartford And Gravesham NHS Trust (GB), Linkou Chang Gung Memorial Hospital (TW), MRC Human Immunology Unit (GB), Centre de Recherche en Cancérologie de Lyon (FR), Policlinico Universitario di Catania (IT), Centre Hospitalier de Valence (FR), Semey Medical University (KZ), Astana Medical University (KZ), Provincial Polyclinical Hospital in Toruń (PL), King's College Hospital (GB), Université Laval (CA), University College London (GB), Gdańsk Medical University (PL)
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