BCR-JAK2 fusion in a myeloproliferative neoplasm with associated eosinophilia

Rong He, Patricia T Greipp, Aruna Rangan, Ming Mai, Dong Chen, Kaaren K. Reichard, Laura L. Nelsen, Animesh D Pardanani, Curtis A. Hanson, David S. Viswanatha

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
JournalCancer genetics
DOIs
StateAccepted/In press - Feb 24 2016

Fingerprint

Janus Kinase 2
Eosinophilia
Neoplasms
Exons
Platelet-Derived Growth Factor beta Receptor
Philadelphia Chromosome
Chromosomes, Human, Pair 9
Gene Rearrangement
Multiplex Polymerase Chain Reaction
Interphase
Hematologic Neoplasms
Reverse Transcriptase Polymerase Chain Reaction
Fluorescence In Situ Hybridization

Keywords

  • B-lymphoblastic leukemia/lymphoma
  • BCR-JAK2 fusion
  • Eosinophilia
  • JAK2
  • Myeloproliferative neoplasm

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

He, R., Greipp, P. T., Rangan, A., Mai, M., Chen, D., Reichard, K. K., ... Viswanatha, D. S. (Accepted/In press). BCR-JAK2 fusion in a myeloproliferative neoplasm with associated eosinophilia. Cancer genetics. https://doi.org/10.1016/j.cancergen.2016.03.002

BCR-JAK2 fusion in a myeloproliferative neoplasm with associated eosinophilia. / He, Rong; Greipp, Patricia T; Rangan, Aruna; Mai, Ming; Chen, Dong; Reichard, Kaaren K.; Nelsen, Laura L.; Pardanani, Animesh D; Hanson, Curtis A.; Viswanatha, David S.

In: Cancer genetics, 24.02.2016.

Research output: Contribution to journalArticle

He, Rong ; Greipp, Patricia T ; Rangan, Aruna ; Mai, Ming ; Chen, Dong ; Reichard, Kaaren K. ; Nelsen, Laura L. ; Pardanani, Animesh D ; Hanson, Curtis A. ; Viswanatha, David S. / BCR-JAK2 fusion in a myeloproliferative neoplasm with associated eosinophilia. In: Cancer genetics. 2016.
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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.",
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AU - He, Rong

AU - Greipp, Patricia T

AU - Rangan, Aruna

AU - Mai, Ming

AU - Chen, Dong

AU - Reichard, Kaaren K.

AU - Nelsen, Laura L.

AU - Pardanani, Animesh D

AU - Hanson, Curtis A.

AU - Viswanatha, David S.

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N2 - 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.

AB - 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.

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