Identification of RNPC3 as a novel JAK2 fusion partner gene in B-acute lymphoblastic leukemia refractory to combination therapy including ruxolitinib

Mol Genet Genomic Med. 2020 Mar;8(3):e1110. doi: 10.1002/mgg3.1110. Epub 2019 Dec 30.

Abstract

Background: Hematopoietic neoplasms with chromosomal translocations involving JAK2 are rare, and most of them show myeloproliferative neoplasm-associated features, followed by B-acute lymphoblastic leukemia (B-ALL). De novo B-ALL cases with JAK2 rearrangements are suggested to be appropriately considered as BCR-ABL1-like B-ALL, but its partners varied.

Methods: Fluorescence in situ hybridization (FISH), RNA sequencing (RNA-Seq), whole-genome sequencing, and reverse transcription polymerase chain reaction (RT-PCR) were performed to identify the pathogenic fusion gene in a 29-year-old woman with relapsed B-ALL and rare t(1;9)(p13;p22) translocation.

Results: We identified RNPC3 as a new JAK2 fusion partner in the patient. She was treated with a combination of chemotherapy and targeted drug ruxolitinib and chimeric antigen receptor T-cell therapy, but failed to achieve complete remission. She had no chance to undergo allogeneic hematopoietic stem cell transplantation and died of disease progression 7 months after the initial diagnosis. Her clinical course demonstrated that this novel RNPC3-JAK2 fusion might portend an unfavorable prognosis.

Conclusion: This finding adds to the expanding compendium of JAK2 fusions found in B-ALL and suggests the potential need for a diagnostic FISH analysis as well as RNA-Seq in the appropriate clinical setting.

Keywords: JAK2; RNPC3; RNPC3-JAK2; B-acute lymphoblastic leukemia.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols
  • Female
  • Humans
  • Janus Kinase 2 / genetics*
  • Leukemia, B-Cell / drug therapy
  • Leukemia, B-Cell / genetics*
  • Leukemia, B-Cell / pathology
  • Nitriles
  • Nuclear Proteins / genetics*
  • Oncogene Fusion*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Pyrazoles / administration & dosage
  • Pyrazoles / therapeutic use
  • Pyrimidines
  • RNA-Binding Proteins / genetics*

Substances

  • Nitriles
  • Nuclear Proteins
  • Pyrazoles
  • Pyrimidines
  • RNA-Binding Proteins
  • RNPC3 protein, human
  • ruxolitinib
  • JAK2 protein, human
  • Janus Kinase 2