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
; 160(5): 255-263, 2020.
Article
in En
| MEDLINE
| ID: mdl-32544910
ABSTRACT
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Translocation, Genetic
/
Leukemia, Myeloid, Acute
/
DNA, Antisense
/
Granulocyte Colony-Stimulating Factor
/
Sequence Deletion
/
Receptors, Kainic Acid
/
Core Binding Factor Alpha 2 Subunit
/
Gene Fusion
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Cytogenet Genome Res
Journal subject:
GENETICA
Year:
2020
Type:
Article