JAK2 V617f in chronic myeloid leukemia: driving force or passive bystander?. Issue 1 (31st December 2022)

• Record Type: Journal Article
• Authors: Tarantini, Francesco; Cumbo, Cosimo; Zagaria, Antonella; Parciante, Elisa; Anelli, Luisa; Coccaro, Nicoletta; Tota, Giuseppina; Minervini, Crescenzio Francesco; Redavid, Immacolata; Rossi, Antonella Russo; Conserva, Maria Rosa; Specchia, Giorgina; Musto, Pellegrino; Albano, Francesco
• Is Part Of: Hematology. Volume 27:Issue 1(2022)
• Page Start: 842
• Page End: 846
• Publication Date: 2022-12-31
• Subjects: Chronic myeloid leukemia -- JAK2 -- CHIP -- BCR-ABL1 -- TFR -- biological age -- CML -- MPNs; Blood -- Diseases -- Periodicals; Hematology -- Periodicals; Blood -- Transfusion -- Periodicals; 616.15005
• DOI: 10.1080/16078454.2022.2108902
• Languages: English
• ISSNs: 1024-5332

Abstract

ABSTRACT: Objectives: BCR-ABL1 and JAK2 V617F coexistence in myeloproliferative neoplasms has been described as concomitant or sequential events. Despite this, we present a unique case of chronic myeloid leukemia (CML) not referable to either of the known scenarios. Methods: BCR-ABL1 molecular monitoring was performed by real-time quantitative PCR (RQ-PCR). At the time of molecular relapse, a targeted next-generation sequencing analysis with a customized panel of 26 genes commonly mutated in myeloid diseases was performed. To investigate the kinetics of the JAK2 variant and its association with the BCR-ABL1 rearrangement, RQ-PCR was performed at different time points during the patient's follow-up. Results: While negative at CML diagnosis, the JAK2 mutation was first detected 9 years later (VAF: 7.2%). The mutational burden of JAK2 remained stable in multiple determinations, with minor fluctuations independent of BCR-ABL1 kinetics. At the last available time point, the patient was in deep molecular response (MR4), the JAK2 mutational burden was 7%, and no clinical-laboratory findings of Ph-MPN were detectable. Discussion: In the presented case, the JAK2 variantoccurring during the course of the disease seems to stay in the shadows of CML, just as a bystander. The impact of this event (that may be considered suggestive of clonal hematopoiesis of indeterminate potential) on the disease outcome, even if seemingly irrelevant, has still to be explored.