Transformation of an Unclassified Myeloproliferative Neoplasm with a Rare BCR-JAK2 Fusion Transcript Resulting from the Translocation (9;22)(p24;q11).

A N Chamseddine,H Tilly,N Contentin,C Kuadjovi,V Camus,C Bastard,D Penther,F Parmentier,P Lenain,F Jardin,P Etancelin

doi:10.1155/2015/252537

A N Chamseddine, H Tilly + Show 9 more

Open Access

https://doi.org/10.1155/2015/252537

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Journal: Case reports in hematology	Publication Date: Jan 1, 2015
Citations: 20	License type: CC BY 3.0

Affiliation: Inserm

Abstract

BCR-ABL1 negative myeloproliferative neoplasms (MPNs) are known to contain alterations of the tyrosine kinase JAK2 (located on 9p24) that result in constitutive activation of the encoded protein. JAK2 fusions are reported in acute and chronic leukemias of myeloid and lymphoid phenotypes. Here, we report an unclassified case of MPN (MPN-U) showing a t(9;22)(p24;q11), which generates a BCR-JAK2 fusion gene by fusing the BCR at intron 13 to JAK2 at intron 17 on the derivative chromosome 22. Most reported JAK2 fusions cases reveal an aggressive clinical course and long-term remissions have only been achieved after allogeneic stem cell transplantation (ASCT). To the best of our knowledge, this is the thirteenth case reported worldwide to describe a BCR-JAK2 fusion transcript in MPN-U. The present report revealed a sustained complete clinical, hematologic, and cytogenetic remission 35 months after diagnosis and ~24 months after ASCT. Regarding BCR-ABL1 negative MPN patients this case report provides strong support for a role of JAK2 activation in the oncogenesis and suggests a possible diagnostic and therapeutic target that should be investigated.

Highlights

Some myeloproliferative neoplasms (MPNs) are Philadelphia- (Ph-) negative, lacking the reciprocal t(9;22)(q34;q11) and its resultant BCR-ABL1 fusion gene
We report a rare case of unclassified MPN (MPN-U) with a t(9;22)(p24;q11) leading to a 5󸀠BCR/3󸀠JAK2 fusion gene producing a fusion transcript that juxtaposed BCR exon 13 and JAK2 exon 17 and subsequently rapidly transformed into a myeloid granulocytic sarcoma
The bone marrow aspiration and biopsy associated with initial molecular blood and medullary analyses led to diagnose an MPN-U

Summary

Introduction

Some myeloproliferative neoplasms (MPNs) are Philadelphia- (Ph-) negative, lacking the reciprocal t(9;22)(q34;q11) and its resultant BCR-ABL1 fusion gene. The most frequent genomic abnormality observed in Ph-negative MPN is a dominant gain-of-function V617F mutation in the JH2 kinase-like domain of JAK2 [1]. There are rare additional mechanisms described in Ph-negative MPNs that activate JAK2, such as chromosomal translocations that cause constitutive dimerization through the replacement of amino terminal sequences with a fusion partner [2, 3]. Six different fusion partners have been associated with JAK2 (RPN1, SSBP2, PAX5, PCM1, BCR, and ETV6). We report a rare case of unclassified MPN (MPN-U) with a t(9;22)(p24;q11) leading to a 5󸀠BCR/3󸀠JAK2 fusion gene producing a fusion transcript that juxtaposed BCR exon 13 and JAK2 exon 17 and subsequently rapidly transformed into a myeloid granulocytic sarcoma. 35 months after diagnosis and ∼24 months after ASCT, a prolonged and sustained complete clinical, hematologic, and cytogenetic remission after undergoing allogeneic stem cell transplantation (ASCT)

Case Presentation

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Discussion