Coexistence of JAK2 or CALR mutation is a rare but clinically important event in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors

Abstract

Introduction: There are 7 designated conditions under the category of myeloproliferative neoplasms (MPN), including chronic myelogenous leukemia (CML) and classical MPN, that is, polycythemia vera (PV), essential thrombocythaemia (ET), and primary myelofibrosis (PMF). Recently, reports about Philadelphia and JAK2 V617F-positive MPN cases have been described in literature. The coexistence of different molecular defects may change the clinical and laboratory manifestation of MPN and may result in an inappropriate interpretation of the response to treatment with tyrosine kinase inhibitors in CML patients.

Methods: The morphological, cytogenetic, and molecular genetic data from a retrospective analysis of 592 adult patients aged 18-86 years diagnosed with CML were analyzed.

Results: In 5 CML patients, the presence of JAK2 V617F or CALR mutation was confirmed. Three of 4 TKI-treated patients did not reach complete hematologic response due to the persistence of thrombocytosis and/or splenomegaly. In all of them (in 3 with JAK2 V617F mutation and 1 with CALR mutation), thrombocytosis was present at the time when complete cytogenetic response was documented. In 3 out of 4 reported CML patients, thrombocytosis and/or splenomegaly were still present even at the time when deep molecular response was reached.

Conclusion: In our opinion, a detailed evaluation and appropriate interpretation of clinical and laboratory data in such a category of patients seem to be extremely important, especially when a decision about the TKI change due to therapy failure is considered.

Keywords: JAK2 and CALR gene mutations; Philadelphia-negative myeloproliferative neoplasm; chronic myeloid leukemia; response criteria.