Frontiers in Cell and Developmental Biology (Mar 2024)

Chronic myeloproliferative neoplasms with concomitant CALR mutation and BCR::ABL1 translocation: diagnostic and therapeutic implications of a rare hybrid disease

  • Magda Zanelli,
  • Valentina Fragliasso,
  • Giuseppe Gaetano Loscocco,
  • Giuseppe Gaetano Loscocco,
  • Francesca Sanguedolce,
  • Giuseppe Broggi,
  • Maurizio Zizzo,
  • Andrea Palicelli,
  • Stefano Ricci,
  • Elisa Ambrogi,
  • Giovanni Martino,
  • Giovanni Martino,
  • Sara Aversa,
  • Francesca Coppa,
  • Pietro Gentile,
  • Fabrizio Gozzi,
  • Rosario Caltabiano,
  • Nektarios Koufopoulos,
  • Aleksandra Asaturova,
  • Luca Cimino,
  • Luca Cimino,
  • Alberto Cavazza,
  • Giulio Fraternali Orcioni,
  • Stefano Ascani

DOI
https://doi.org/10.3389/fcell.2024.1391078
Journal volume & issue
Vol. 12

Abstract

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Myeloproliferative neoplasms (MPNs) are subdivided into Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) and Ph-negative MPNs. BCR::ABL1 translocation is essential for the development and diagnosis of CML; on the other hand, the majority of Ph-negative MPNs are characterized by generally mutually exclusive mutations of Janus kinase 2 (JAK2), calreticulin (CALR), or thrombopoietin receptor/myeloproliferative leukemia (MPL). CALR mutations have been described essentially in JAK2 and MPL wild-type essential thrombocythemia and primary myelofibrosis. Rarely coexisting CALR and MPL mutations have been found in Ph-negative MPNs. BCR::ABL1 translocation and JAK2 mutations were initially considered mutually exclusive genomic events, but a discrete number of cases with the combination of these genetic alterations have been reported. The presence of BCR::ABL1 translocation with a coexisting CALR mutation is even more uncommon. Herein, starting from a routinely diagnosed case of CALR-mutated primary myelofibrosis subsequently acquiring BCR::ABL1 translocation, we performed a comprehensive review of the literature, discussing the clinicopathologic and molecular features, as well as the outcome and treatment of cases with BCR::ABL1 and CALR co-occurrence.

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