Myeloproliferative neoplasms with concomitant chronic myeloid leukemia are associated with TKI resistance and poor outcomes
Year: 2026
Type: article
Study design: Observational Study
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).
Source: Leukemia
Authors: Laura Li Gagnon, Andrea Duminuco, Fabio Stagno, Marta Sobas, Mikhail Fominykh, Andres Virchis, Franck-Emmanuel Nicolini, Julie Hildt, Helen Bentley, Anna L. Godfrey, Lee-Yung Shih, Ashlyn Chee, Adam Mead, Krzysztof Lewandowski, Patryk Sobieralski, Guy Hannah, Yasmin Reyal, Thomas Cummin, Jaroslaw Piszcz, Kawai Yip, Rebecca Frewin, Srinivasan Narayanan, Deborah Rahman, Alero Ajayi, Paul Cervi, Jennifer Byrne, Tom Taylor, Weronika Lebowa, Jiri Pavlu, Siamak Arami, Mansour Ceesay, Dominik Chraniuk, Robert Delage, Annalisa Condorelli, Clémence Santana, Deepti H. Radia, Hugues de Lavallade, Dragana Milojkovic, Claire Harrison, Patrick Harrington
Institutions: Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, Université Laval, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco", University of Messina, University of Wrocław, Nicolaus Copernicus University, Wroclaw Medical University, Collegium Medicum in Bydgoszcz, Semey Medical University, University College London Hospitals NHS Foundation Trust, Royal Free London NHS Foundation Trust, Centre Léon Bérard, Cambridge University Hospitals NHS Foundation Trust, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan Chang Gung Memorial Hospital, Linkou Chang Gung Memorial Hospital, Churchill Hospital, University of Oxford, MRC Weatherall Institute of Molecular Medicine, Poznan University of Medical Sciences, Gdańsk Medical University, King's College Hospital, St George’s University Hospitals NHS Foundation Trust, Portsmouth Hospitals NHS Trust, Medical University of Białystok, Dartford And Gravesham NHS Trust, Gloucestershire Hospitals NHS Foundation Trust, University Hospital Southampton NHS Foundation Trust, Southend University Hospital NHS Foundation Trust, Southend Hospital, Nottingham University Hospitals NHS Trust, Jagiellonian University, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London North West Healthcare NHS Trust, Provincial Polyclinical Hospital in Toruń, Ospedale Papa Giovanni XXIII, Centre Hospitalier de Valence, King's College London
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,190
OpenAlex ID: W7141708221