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

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=12

YEAR=2024

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2024.1391078

DOI=10.3389/fcell.2024.1391078

ISSN=2296-634X

ABSTRACT=<p>Myeloproliferative neoplasms (MPNs) are subdivided into Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) and Ph-negative MPNs. <italic>BCR::ABL1</italic> 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 (<italic>JAK2</italic>), calreticulin (<italic>CALR</italic>), or thrombopoietin receptor/myeloproliferative leukemia (<italic>MPL</italic>). <italic>CALR</italic> mutations have been described essentially in <italic>JAK2</italic> and <italic>MPL</italic> wild-type essential thrombocythemia and primary myelofibrosis. Rarely coexisting <italic>CALR</italic> and <italic>MPL</italic> mutations have been found in Ph-negative MPNs. <italic>BCR::ABL1</italic> translocation and <italic>JAK2</italic> 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 <italic>BCR::ABL1</italic> translocation with a coexisting <italic>CALR</italic> mutation is even more uncommon. Herein, starting from a routinely diagnosed case of <italic>CALR</italic>-mutated primary myelofibrosis subsequently acquiring <italic>BCR::ABL1</italic> 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 <italic>BCR::ABL1</italic> and <italic>CALR</italic> co-occurrence.</p>