TY - JOUR
T1 - Truncated runx1 generated by the fusion of runx1 to antisense grik2 via a cryptic chromosome translocation enhances sensitivity to granulocyte colony-stimulating factor
AU - Abe, Akihiro
AU - Yamamoto, Yukiya
AU - Katsumi, Akira
AU - Yamamoto, Hideyuki
AU - Okamoto, Akinao
AU - Inaguma, Yoko
AU - Iriyama, Chisako
AU - Tokuda, Masutaka
AU - Okamoto, Masataka
AU - Emi, Nobuhiko
AU - Tomita, Akihiro
N1 - Funding Information:
This work was supported by JSPS KAKENHI Grant Number 16K09860 to A.A., a Grant-in-Aid from Fujita Health University to N.E., and the Program for the Strategic Research Foundation at Private Universities supported by the Ministry of Education, Culture, Sports, Science, and Technology (MEXT).
Publisher Copyright:
© 2020
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
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U2 - 10.1159/000508012
DO - 10.1159/000508012
M3 - Article
C2 - 32544910
AN - SCOPUS:85087341891
VL - 160
SP - 255
EP - 263
JO - Cytogenetic and Genome Research
JF - Cytogenetic and Genome Research
SN - 1424-8581
IS - 5
ER -