Truncated RUNX1 Generated by the Fusion of RUNX1 to Antisense GRIK2 via a Cryptic Chromosome Translocation Enhances Sensitivity to Granulocyte Colony-Stimulating Factor

Cytogenet Genome Res. 2020;160(5):255-263. doi: 10.1159/000508012. Epub 2020 Jun 16.


Fusions of the Runt-related transcription factor 1 (RUNX1) with different partner genes have been associated with various hematological disorders. Interestingly, the C-terminally truncated form of RUNX1 and RUNX1 fusion proteins are similarly considered important contributors to leukemogenesis. Here, we describe a 59-year-old male patient who was initially diagnosed with acute myeloid leukemia, inv(16)(p13;q22)/CBFB-MYH11 (FAB classification M4Eo). He achieved complete remission and negative CBFB-MYH11 status with daunorubicin/cytarabine combination chemotherapy but relapsed 3 years later. Cytogenetic analysis of relapsed leukemia cells revealed CBFB-MYH11 negativity and complex chromosomal abnormalities without inv(16)(p13;q22). RNA-seq identified the glutamate receptor, ionotropic, kinase 2 (GRIK2) gene on 6q16 as a novel fusion partner for RUNX1 in this case. Specifically, the fusion of RUNX1 to the GRIK2 antisense strand (RUNX1-GRIK2as) generated multiple missplicing transcripts. Because extremely low levels of wild-type GRIK2 were detected in leukemia cells, RUNX1-GRIK2as was thought to drive the pathogenesis associated with the RUNX1-GRIK2 fusion. The truncated RUNX1 generated from RUNX1-GRIK2as induced the expression of the granulocyte colony-stimulating factor (G-CSF) receptor on 32D myeloid leukemia cells and enhanced proliferation in response to G-CSF. In summary, the RUNX1-GRIK2as fusion emphasizes the importance of aberrantly truncated RUNX1 in leukemogenesis.

Keywords: GRIK2; RUNX1; Acute myeloid leukemia; Missplicing; Translocations.

Publication types

  • Case Reports

MeSH terms

  • Cell Proliferation / drug effects
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • DNA, Antisense / genetics*
  • Gene Fusion / genetics*
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Receptors, Granulocyte Colony-Stimulating Factor / biosynthesis
  • Receptors, Granulocyte Colony-Stimulating Factor / metabolism
  • Receptors, Kainic Acid / genetics*
  • Sequence Deletion / genetics*
  • Translocation, Genetic / genetics*


  • Core Binding Factor Alpha 2 Subunit
  • DNA, Antisense
  • Gluk2 kainate receptor
  • RNA, Messenger
  • RUNX1 protein, human
  • Receptors, Granulocyte Colony-Stimulating Factor
  • Receptors, Kainic Acid
  • Granulocyte Colony-Stimulating Factor