V617f in chronic myeloid leukemia: driving force or passive bystander?

Objectives: and 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: 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 variant and its association with the rearrangement, RQ-PCR was performed at different time points during the patient's follow-up.

Results: While negative at CML diagnosis, the mutation was first detected 9 years later (VAF: 7.2%). The mutational burden of remained stable in multiple determinations, with minor fluctuations independent of kinetics. At the last available time point, the patient was in deep molecular response (MR4), the mutational burden was 7%, and no clinical-laboratory findings of Ph-MPN were detectable.

Discussion: In the presented case, the 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.