BCR-JAK2 fusion in a myeloproliferative neoplasm with associated eosinophilia

Abstract

Janus kinase 2 (JAK2) is located on chromosome 9 at band p24 and JAK2V617F is the most common mutation in Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPN). However, rearrangement of JAK2 is a rare event. We report a case of myeloproliferative neoplasm, unclassifiable (MPN-U) with BCR-JAK2 fusion confirmed by molecular studies. Conventional chromosome analysis (CC) revealed t(9;22)(p24;q11.2) and fluorescence in situ hybridization (FISH) showed a JAK2 gene rearrangement in 88% of interphase nuclei. The BCR-JAK2 fusion was confirmed by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) and demonstrated two in-frame 5'BCR/3'JAK2 transcripts with BCR exon 1 juxtaposed to JAK2 exon 15 and exon 17, respectively. Our results, together with literature review, reveal BCR-JAK2 fusions as oncogenic genetic alterations that are associated with myeloid or lymphoid neoplasms and are frequently characterized by eosinophilia. Further, patients with BCR-JAK2 are candidates for JAK2 inhibitor therapy. Given the distinct clinical and pathological characteristics, we believe that hematological neoplasms harboring BCR-JAK2 should be included as an additional distinct entity to the current WHO category of "myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR", and testing for a JAK2 fusion should be pursued in neoplasms with a karyotypic 9p24 abnormality.

Keywords: B-lymphoblastic leukemia/lymphoma; BCR–JAK2 fusion; JAK2; eosinophilia; myeloproliferative neoplasm.