Concomitant BCR-ABL1 Translocation and JAK2V617F Mutation in Three Patients with Myeloproliferative Neoplasms

Abstract

Chronic myeloproliferative neoplasms (MPN) are clonal disorders of hematopoietic stem cells, which fall into distinct categories based on a number of characteristics including the presence of the BCR-ABL1 gene fusion (chronic myelogenous leukemia) or the JAK2(V617F) mutation (polycythemia vera, primary myelofibrosis, and essential thrombocythemia). One of the criteria in the 2008 World Health Organization Classification divides MPN into different categories based on the presence of an underlying genetic abnormality, however the WHO does not currently address the classification of myeloproliferative neoplasms that have more than one genetic abnormality. The coexistence of a JAK2(V617F) mutation and BCR-ABL1 is rare, and to our knowledge, less than 25 cases have been reported in the literature. Our case series examines the clinical, histopathologic, and genetic features of 3 patients with myeloproliferative neoplasms characterized by concomitant BCR-ABL1 and JAK2(V617F). The implications for diagnosis and treatment of patients with concomitant BCR-ABL1 and JAK2(V617F) are discussed as well as how the BCR-ABL1 and JAK2(V617F)-positive clones may be related to one another.

Myelofibrosis-associated complications: pathogenesis, clinical manifestations, and effects on outcomes

“…An increasing number of mutations that directly or indirectly affect JAK-STAT signaling are being implicated in the pathobiology of MPNs, including PMF,33–35 revealing an unexpected genetic and epigenetic complexity of these neoplasms 29,36. Notably, findings of multiple mutations in the same patient33 are consistent with the notion that MPNs are multiclonal diseases with as yet poorly understood clonal hierarchies 37–39…”

Two Cases of Myeloproliferative Neoplasm with a ConcurrentJAK2V617FMutation andBCR/ABLTranslocation without Chronic Myelogenous Leukemia Phenotype Acquisition during Hydroxyurea Treatment

“…Although the 2008 WHO classification does not include MPNs with more than 1 genetic aberration as a distinct disease entity, some cases with coexistence of JAK2 V617F mutation and BCR/ABL translocation have been recently reported and up to 28 cases have been previously reported [3-20]. Among these reports, the majority of the patients either had pre-existing BCR/ABL -positive CML and developed JAK2 V617F mutation while undergoing tyrosine kinase inhibitor treatment [4-7] or developed BCR/ABL -positive CML with a pre-existing JAK2 V617F mutation-positive MPN [8-12].…”

“…Among these reports, the majority of the patients either had pre-existing BCR/ABL -positive CML and developed JAK2 V617F mutation while undergoing tyrosine kinase inhibitor treatment [4-7] or developed BCR/ABL -positive CML with a pre-existing JAK2 V617F mutation-positive MPN [8-12]. In contrast, a small number of patients showed simultaneous occurrence of both JAK2 V617F mutation and BCR/ABL translocation, with a CML phenotype in the bone marrow (BM) with development of symptoms or morphology associated with JAK2 V617F mutation, and with MPN only after imatinib treatment [3, 6, 13-15]. We report 2 MPN cases that were simultaneously positive for both JAK2 V617F mutation and BCR/ABL translocation and that did not acquire the CML phenotype during hydroxyurea (Korea United Pharm, Seoul, Korea) treatment.…”

“…In contrast, 9 of the 28 patients showed JAK2 V617F mutation-positive MPN phenotype at initial diagnosis and developed BCR/ABL -positive CML during hydroxyurea treatment. Finally, at initial diagnosis, 4 patients showed mixed phenotype associated with both BCR/ABL -positive CML and JAK2 V617F mutation-positive MPN [3]. …”

“…JAK2 V617F mutation positive) [4-12]. The second hypothesis proposes that a single clone concurrently possesses both the BCR/ABL translocation and JAK2 V617F mutation [3, 13-15]. This hypothesis was supported by a recent study, which reported that the BCR/ABL translocation occurred in a pre-existing JAK2 V617F mutation-positive clone [18].…”