Clonal megakaryocyte dysplasia with normal blood values: a covert, thrombosisprone, early myeloproliferative neoplasm

To improve our knowledge on the epidemiological, clinical and pathobiological profile of clonal megakaryocyte dysplasia with normal blood values (CMD-NBV), a BCR::ABLnegative myeloproliferative neoplasms (MPNs) clinical variant, we here report a series of 30 consecutive subjects with CMD-NBV. Sixteen subjects were men and the median age was 48 years (IQR, 39-53 years). A situation-driven diagnosis (70% of cases had the diagnosis triggered by an incidental or symptomatic venous or arterial thrombosis), high incidence of thrombotic events (6.5 events x 100 subject-years), and indolent disease (the 10-year CMD-NBV specific survival was 100%) were common. Nineteen subjects had a high BMI at diagnosis and 14 had ≥ 1 Charlson co-morbidities. In 21 the driver variant was JAK2V617F with a median variant allele frequency at diagnosis of 8.9% (IQR, 5.4- 18.4%). Six of 24 (25%) subjects with data on next generation sequencing (NGS) for myeloid neoplasm-related genes had ≥ 1 pathogenic somatic variant in ASXL1, TET2, DNMT3A or SRSF2, a frequency in the lower range of values of chronic MPNs. Twelve putative germline, non-pathogenic, missense variants in ASXL1, TET2, DNMT3A, RUNX1, CUX1, ABL1, NF1, KIT and CSF3R or 5' UTR in NF1 and 3' UTR in ASXL1 were detected in 10 of 24 (42%) subjects. These data further support identification of CMD-NBV as a distinct entity.

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Publication Details

Journal
Haematologica
Published
2025-11-20
DOI
https://doi.org/10.3324/haematol.2025.288681
Primary Topic
Myeloproliferative Neoplasms: Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
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article

Clonal megakaryocyte dysplasia with normal blood values: a covert, thrombosisprone, early myeloproliferative neoplasm

Carlotta Abbà, Vittorio Rosti, Maria Chiara Finazzi, Margherita Massa et al.
Haematologica
Myeloproliferative Neoplasms: Diagnosis and Treatment
article

Clonal megakaryocyte dysplasia with normal blood values: a covert, thrombosisprone, early myeloproliferative neoplasm

Carlotta Abbà, Vittorio Rosti, Maria Chiara Finazzi, Margherita Massa, Lorena Pergola, Caterina Tatarelli, Anna Gallì, Valerio De Stefano, Alessandro Rambaldi, Andrea Gianatti, Adriana Carolei, Paolo Catarsi, Tiziano Barbui, Luca Malcovati, Rita Campanelli, Alessandro Inzoli, Michela Bardelli, Robert Peter Gale, Giovanni Barosi, Annalisa Condorelli, Silvia Salmoiraghi, Martina Gandossini
article en

Abstract

To improve our knowledge on the epidemiological, clinical and pathobiological profile of clonal megakaryocyte dysplasia with normal blood values (CMD-NBV), a BCR::ABLnegative myeloproliferative neoplasms (MPNs) clinical variant, we here report a series of 30 consecutive subjects with CMD-NBV. Sixteen subjects were men and the median age was 48 years (IQR, 39-53 years). A situation-driven diagnosis (70% of cases had the diagnosis triggered by an incidental or symptomatic venous or arterial thrombosis), high incidence of thrombotic events (6.5 events x 100 subject-years), and indolent disease (the 10-year CMD-NBV specific survival was 100%) were common. Nineteen subjects had a high BMI at diagnosis and 14 had ≥ 1 Charlson co-morbidities. In 21 the driver variant was JAK2V617F with a median variant allele frequency at diagnosis of 8.9% (IQR, 5.4- 18.4%). Six of 24 (25%) subjects with data on next generation sequencing (NGS) for myeloid neoplasm-related genes had ≥ 1 pathogenic somatic variant in ASXL1, TET2, DNMT3A or SRSF2, a frequency in the lower range of values of chronic MPNs. Twelve putative germline, non-pathogenic, missense variants in ASXL1, TET2, DNMT3A, RUNX1, CUX1, ABL1, NF1, KIT and CSF3R or 5' UTR in NF1 and 3' UTR in ASXL1 were detected in 10 of 24 (42%) subjects. These data further support identification of CMD-NBV as a distinct entity.

Haematologica
University of Bergamo (IT), Centro Studi GISED (IT), University of Milan (IT), University of Pavia (IT), Agostino Gemelli University Polyclinic (IT), Ospedale Papa Giovanni XXIII (IT), CTO Andrea Alesini (IT), Azienda Ospedaliera Ospedale Maggiore (IT), Policlinico San Matteo Fondazione (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Imperial College London (GB)
Associazione Italiana per la Ricerca sul Cancro
Openalex Percentile: Top 49%
Myeloproliferative Neoplasms: Diagnosis and Treatment
DOIOpen Access PDFOpenAlex
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