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TLE3 Is a Novel Fusion Partner of JAK2 in Myeloid/Lymphoid Neoplasm With Eosinophilia Responding to JAK2 Inhibition

Lazarevic, Vladimir LU orcid ; Lilljebjörn, Henrik LU orcid ; Olsson-Arvidsson, Linda LU ; Orsmark-Pietras, Christina LU and Ågerstam, Helena LU (2024) In Genes Chromosomes and Cancer 63(8). p.1-8
Abstract

Chromosomal rearrangements involving Janus kinase 2 (JAK2) are rare but recurrent findings in lymphoid or myeloid neoplasia. Detection of JAK2 fusion genes is important as patients with aberrantly activated JAK2 may benefit from treatment with tyrosine kinase inhibitors such as ruxolitinib. Here, we report a novel fusion gene between the transcriptional co-repressor-encoding gene transducin-like enhancer of split 3 (TLE3) and JAK2 in a patient initially diagnosed with chronic eosinophilic leukemia with additional mutations in PTPN11 and NRAS. The patient was successfully treated with the JAK2 inhibitor ruxolitinib for 8 months before additional somatic mutations were acquired and the disease progressed into an acute lymphoblastic T-cell... (More)

Chromosomal rearrangements involving Janus kinase 2 (JAK2) are rare but recurrent findings in lymphoid or myeloid neoplasia. Detection of JAK2 fusion genes is important as patients with aberrantly activated JAK2 may benefit from treatment with tyrosine kinase inhibitors such as ruxolitinib. Here, we report a novel fusion gene between the transcriptional co-repressor-encoding gene transducin-like enhancer of split 3 (TLE3) and JAK2 in a patient initially diagnosed with chronic eosinophilic leukemia with additional mutations in PTPN11 and NRAS. The patient was successfully treated with the JAK2 inhibitor ruxolitinib for 8 months before additional somatic mutations were acquired and the disease progressed into an acute lymphoblastic T-cell leukemia/lymphoma. The present case shows similarities to previously reported cases with PCM1::JAK2 and BCR::JAK2 with regard to disease phenotype and response to ruxolitinib, and importantly, provides an example that also patients harboring other JAK2 fusion genes may benefit from treatment with JAK2 inhibitors.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
eosinophilia, JAK2, MPN, ruxolitinib, TLE3
in
Genes Chromosomes and Cancer
volume
63
issue
8
article number
e23261
pages
1 - 8
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:39105620
  • scopus:85200657533
ISSN
1045-2257
DOI
10.1002/gcc.23261
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2024 The Author(s). Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.
id
e6289ff9-ca79-4c80-a07a-59dfa78238f5
date added to LUP
2024-08-14 16:43:30
date last changed
2024-08-16 02:21:42
@article{e6289ff9-ca79-4c80-a07a-59dfa78238f5,
  abstract     = {{<p>Chromosomal rearrangements involving Janus kinase 2 (JAK2) are rare but recurrent findings in lymphoid or myeloid neoplasia. Detection of JAK2 fusion genes is important as patients with aberrantly activated JAK2 may benefit from treatment with tyrosine kinase inhibitors such as ruxolitinib. Here, we report a novel fusion gene between the transcriptional co-repressor-encoding gene transducin-like enhancer of split 3 (TLE3) and JAK2 in a patient initially diagnosed with chronic eosinophilic leukemia with additional mutations in PTPN11 and NRAS. The patient was successfully treated with the JAK2 inhibitor ruxolitinib for 8 months before additional somatic mutations were acquired and the disease progressed into an acute lymphoblastic T-cell leukemia/lymphoma. The present case shows similarities to previously reported cases with PCM1::JAK2 and BCR::JAK2 with regard to disease phenotype and response to ruxolitinib, and importantly, provides an example that also patients harboring other JAK2 fusion genes may benefit from treatment with JAK2 inhibitors.</p>}},
  author       = {{Lazarevic, Vladimir and Lilljebjörn, Henrik and Olsson-Arvidsson, Linda and Orsmark-Pietras, Christina and Ågerstam, Helena}},
  issn         = {{1045-2257}},
  keywords     = {{eosinophilia; JAK2; MPN; ruxolitinib; TLE3}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1--8}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Genes Chromosomes and Cancer}},
  title        = {{TLE3 Is a Novel Fusion Partner of JAK2 in Myeloid/Lymphoid Neoplasm With Eosinophilia Responding to JAK2 Inhibition}},
  url          = {{http://dx.doi.org/10.1002/gcc.23261}},
  doi          = {{10.1002/gcc.23261}},
  volume       = {{63}},
  year         = {{2024}},
}