BCR-JAK2 fusion as a result of a translocation (9;22)(p24;q11.2) in a patient with CML-like myeloproliferative disease

Mohamed M Elnaggar,Sally Agersborg,Trilochan Sahoo,Alexis Leal,Isabel Zorrilla,Ati Girgin,Ronjay Rakkhit,Wanlong Ma

doi:10.1186/1755-8166-5-23

Abstract

Translocation (9;22)(q34;q11.2) resulting in BCR/ABL1 fusion at the molecular level is the hallmark of chronic myelogenous leukemia (CML). Variants of the Philadelphia translocation and complex translocations involving BCR have been reported in myeloproliferative disorders (MPD). A rare translocation, t(9;22)(p24;q11.2), resulting in a novel BCR-JAK2 fusion has been reported in a handful of cases of CML and acute myelogenous leukemia (AML). We present clinical-pathological and cytogenetic evaluation of a patient with Philadelphia-chromosome negative CML/MPD harboring a t(9;22)(p24;q11.2) resulting in BCR-JAK2 fusion. Fluorescence in situ hybridization and molecular characterization of the translocation confirmed a BCR-JAK2 fusion and helped delineate the breakpoints upstream of exon 1 of minor cluster region of BCR gene and likely intron 18 of the JAK2 gene, resulting in an in-frame transcript This case provides convincing support, along with two previous case-reports, for a role for activation of the Janus kinase 2 in evolution of myeloproliferative disease. The recurrent, albeit rare, nature of the breakpoints within BCR and JAK2 suggests a potential new diagnostic target that should be interrogated in Ph-negative CML/MPD patients.

Highlights

The Philadelphia translocation is one of the most well characterized cytogenetic aberrations seen in a vast majority of cases of chronic myelogenous leukemia
A presumptive diagnosis of myeloproliferative disorders (MPD) and possible BCR-Janus kinase 2 gene (JAK2) fusion was suspected from chromosome and Fluorescence in-situ hybridization (FISH) analysis revealing a translocation t(9;22)( p24;q11.2)
Though relatively rare and likely under-diagnosed, the BCR-JAK2 fusion event in this case with chronic myeloid leukemia (CML)/MPD adds to the spectrum of rare yet recurrent translocation partners for each of the genes, respectively

Summary

Introduction

The Philadelphia translocation is one of the most well characterized cytogenetic aberrations seen in a vast majority of cases of chronic myelogenous leukemia. We report a case of chronic myeloid leukemia (CML) with a translocation (9;22)(p24;q11.2), resulting in BCR-JAK2 fusion, as a sole cytogenetic abnormality. The fusion gene was confirmed at the molecular level This case report provides additional strong support for a role for JAK2 activation in chronic myeloproliferative disorders. Routine labs showed an elevated white blood cell count of 36,600, low hemoglobin of 10.32 g/dL and normal platelets of 275 k/uL. Bone marrow aspiration and biopsy showed hypercellularity with striking myeloid hyperplasia with complete granulocytic maturation to segmented neutrophils (Figure 1). A potential BCR-JAK2 fusion was suspected based on the chromosome analysis revealing a translocation t(9;22)( p24; q11.2) and clinical diagnosis of MPD. A total of six individual RT-PCR reactions were designed to determine the possible breakpoints within BCR and JAK2 resulting in a fusion transcript. We used 2 reverse primers mapping to exon 15 (5’- CCA TGC CAA CTG TTT AGC AA-3’) and exon 20 of JAK2 gene (5’- TCA TAC CGG CAC ATC TCC ACA C-3’) [NC_000009.11] [5,6]

Results

Conclusions

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