Identification of a novel GOLGA4-JAK2 fusion gene in B-cell acute lymphoblastic leukaemia

Br J Haematol. 2022 Feb;196(3):700-705. doi: 10.1111/bjh.17910. Epub 2021 Oct 25.

Abstract

Rearrangements of Janus kinase 2 (JAK2r) form a subtype of acute lymphoblastic leukaemia (ALL) associated with poor patient outcomes. We present a high-risk case of B-cell ALL (B-ALL) where retrospective mRNA sequencing identified a novel GOLGA4-JAK2 fusion gene. Expression of GOLGA4-JAK2 in murine pro-B cells promoted factor-independent growth, implicating GOLGA4-JAK2 as an oncogenic driver. Cells expressing GOLGA4-JAK2 demonstrated constitutive activation of JAK/STAT signalling and were sensitive to JAK inhibitors. This study contributes to the diverse collection of JAK2 fusion genes identified in B-ALL and supports the incorporation of JAK inhibitors into treatment strategies to improve outcomes for this subtype.

Keywords: JAK2; acute leukaemia; chromosomal; gene fusion; rearrangements; targeted therapy; tyrosine kinases.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / genetics*
  • Biomarkers, Tumor*
  • Biopsy
  • Bone Marrow / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • DNA Mutational Analysis
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Rearrangement
  • Genetic Predisposition to Disease
  • Humans
  • Janus Kinase 2 / genetics*
  • Male
  • Mice
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Prognosis
  • Protein Kinase Inhibitors
  • Signal Transduction

Substances

  • Autoantigens
  • Biomarkers, Tumor
  • GOLGA4 protein, human
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • JAK2 protein, human
  • Janus Kinase 2