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Leukemic evolution of polycythemia vera and essential thrombocythemia: genomic profiles predict time to transformation.

ABSTRACT: Among myeloproliferative neoplasms, polycythemia vera (PV) and essential thrombocythemia (ET) are the 2 entities associated with the most chronic disease course. Leukemic evolution occurs rarely but has a grim prognosis. The interval between diagnosis and leukemic evolution is highly variable, from a few years to >20 years. We performed a molecular evaluation of 49 leukemic transformations of PV and ET by targeted next-generation sequencing. Using a hierarchical classification, we identified 3 molecular groups associated with a distinct time to leukemic transformation. Short-term transformations were mostly characterized by a complex molecular landscape and mutations in IDH1/2, RUNX1, and U2AF1 genes, whereas long-term transformations were associated with mutations in TP53, NRAS, and BCORL1 genes. Studying paired samples from chronic phase and transformation, we detected some mutations already present during the chronic phase, either with a significant allele burden (short-term transformation) or with a very low allele burden (especially TP53 mutations). However, other mutations were not detected even 1 year before leukemic transformation. Our results suggest that the leukemic transformation of PV and ET may be driven by distinct time-dependent molecular mechanisms.

SUBMITTER: Luque Paz D

PROVIDER: S-EPMC7556129 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Leukemic evolution of polycythemia vera and essential thrombocythemia: genomic profiles predict time to transformation.

Luque Paz Damien D Jouanneau-Courville Rébecca R Riou Jérémie J Ianotto Jean-Christophe JC Boyer Françoise F Chauveau Aurélie A Renard Maxime M Chomel Jean-Claude JC Cayssials Emilie E Gallego-Hernanz Maria-Pilar MP Pastoret Cédric C Murati Anne A Courtier Frédéric F Rousselet Marie-Christine MC Quintin-Roué Isabelle I Cottin Laurane L Orvain Corentin C Thépot Sylvain S Chrétien Jean-Marie JM Delneste Yves Y Ifrah Norbert N Blanchet Odile O Hunault-Berger Mathilde M Lippert Eric E Ugo Valérie V

Blood advances 20201001 19

Among myeloproliferative neoplasms, polycythemia vera (PV) and essential thrombocythemia (ET) are the 2 entities associated with the most chronic disease course. Leukemic evolution occurs rarely but has a grim prognosis. The interval between diagnosis and leukemic evolution is highly variable, from a few years to >20 years. We performed a molecular evaluation of 49 leukemic transformations of PV and ET by targeted next-generation sequencing. Using a hierarchical classification, we identified 3 m ...[more]

PMID: 33035330

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Project description:Polycythemia vera (PV) and essential thrombocythemia (ET) are rare myeloproliferative neoplasms (MPN) in children, adolescents and young adults. No recommendations are available concerning these patients' management. Transposing to children the knowledge established in adult patients is not acceptable. For a better understanding of difficulties encountered by pediatricians and adult hematologists, we conducted a national practice analysis concerning follow-up of patients under 18 diagnosed with ET or PV, in France. Then, we present data from a multicentric, descriptive, retrospective study, including 17 patients with ET or PV, diagnosed under 18, coming from 7 hematopediatric departments in France. Interviewed physicians reported a lack of expertise and theoretical training in the hematological field to diagnose and follow children with MPNs. Data from 17 patients (15 ET, 2 PV) confirmed a high proportion of asymptomatic patients at the time of diagnosis (41%). Proportion of "triple-negative" patients (59%) was higher than in adult cohorts. 60% of patients underwent a bone marrow biopsy and 31% of cases were discussed during a multi-disciplinary staff meeting. 76.5% patients were treated, with a high frequency of antithrombotic and cytoreductive drugs. No complications were observed during the 45 months of median follow-up.ConclusionPhysicians insisted on the need for training. Only the accumulation of descriptions of MPNs in children will lead to a better management of these diseases. Considering the small proportion of pediatric patients with complications after diagnosis, rapid therapeutic de-escalation seems essential to consider during the follow-up in a close collaboration with adult hematologists.What is known• Myeloproliferativ neoplams are rare and chronic deseases, most of the time affecting adults but also found in few pediatric patients. • There are no recommendations for the diagnosis, therapeutic management or follow-up of children with polycythemia vera or essential thrombocythemia.What is new• Find out how adult haematologists and paediatricians feel about the management and follow-up of paediatric patients with myeloproliferative syndrome through a national practice analysis. • Description of the "real life" follow-up of children with polycythemia vera or essential thrombocythemia in France.

Dataset Information

Leukemic evolution of polycythemia vera and essential thrombocythemia: genomic profiles predict time to transformation.

Publications

Leukemic evolution of polycythemia vera and essential thrombocythemia: genomic profiles predict time to transformation.

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