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=Volume 12 - 2024

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=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 side 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 this genetic alterations has 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 clinicopathological and molecular features as well as outcome and treatment of cases with BCR::ABL1 and CALR co-occurrence. Eliminato: Interestingly in both the group of CML preceding Ph-336 negative MPN and the group with concomitant CML and Ph-negative 337 MPN, no cases of CALR type 2 were found; whereas in the group of 338 Ph-negative MPN preceding CML, CALR type 1 and CALR type 2 339 were equally represented.