AUTHOR=Zanelli Magda , Bisagni Alessandra , Sanguedolce Francesca , Broggi Giuseppe , Fragliasso Valentina , Zizzo Maurizio , Palicelli Andrea , Martino Giovanni , Cresta Camilla , Caprera Cecilia , Corsi Matteo , Gentile Pietro , Gozzi Fabrizio , Trombetta Domenico , Parente Paola , Caltabiano Rosario , Koufopoulos Nektarios , Cimino Luca , Cavazza Alberto , Fraternali Orcioni Giulio , Ascani Stefano 

TITLE=Co-occurrence of JAK2-V617 F mutation and BCR::ABL1 translocation in chronic myeloproliferative neoplasms: a potentially confounding genetic combination

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2024

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1329298

DOI=10.3389/fonc.2023.1329298

ISSN=2234-943X

ABSTRACT=<p>Myeloproliferative neoplasms (MPNs) are classified into Philadelphia (Ph) chromosome–positive chronic myeloid leukemia (CML) and Ph-negative MPNs. <italic>BCR::ABL1</italic> translocation is the key genetic event of CML, whereas <italic>JAK2/MPL/CALR</italic> mutations are molecular aberrations of Ph-negative MPNs. Despite initially considered mutually exclusive genetic aberrations, the co-occurrence of <italic>BCR::ABL1</italic> and <italic>JAK2</italic> has been reported in a limited number of cases. The two genetic alterations may be identified either at the same time or <italic>JAK2</italic> aberration may be detected in patients with a previous CML treated with tyrosine kinase inhibitors or, finally, <italic>BCR::ABL1</italic> translocation occurs in patients with a history of <italic>JAK2</italic>-positive MPN. This combination of genomic alterations is potentially confounding with clinical manifestations often misinterpreted either as disease progression or drug resistance, therefore leading to inappropriate patient’s treatment. Our systematic review aims to improve hematologist and pathologist knowledge on this rare subset of patients. Starting from the presentation of two additional cases from our routine daily practice, we focus mainly on clinical, laboratory, and bone marrow histological findings, which may represent useful clues of <italic>BCR::ABL1</italic> and <italic>JAK2</italic> co-occurrence. The interaction between <italic>JAK2</italic> and <italic>BCR::ABL1</italic> clones during the disease course as well as therapy and outcome are presented.</p>