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HOXA9 promotes MYC-mediated leukemogenesis by maintaining gene expression for multiple anti-apoptotic pathways.
- Source :
-
ELife [Elife] 2021 Jul 26; Vol. 10. Date of Electronic Publication: 2021 Jul 26. - Publication Year :
- 2021
-
Abstract
- HOXA9 is often highly expressed in leukemias. However, its precise roles in leukemogenesis remain elusive. Here, we show that HOXA9 maintains gene expression for multiple anti-apoptotic pathways to promote leukemogenesis. In MLL fusion-mediated leukemia, MLL fusion directly activates the expression of MYC and HOXA9. Combined expression of MYC and HOXA9 induced leukemia, whereas single gene transduction of either did not, indicating a synergy between MYC and HOXA9. HOXA9 sustained expression of the genes implicated in the hematopoietic precursor identity when expressed in hematopoietic precursors, but did not reactivate it once silenced. Among the HOXA9 target genes, BCL2 and SOX4 synergistically induced leukemia with MYC . Not only BCL2, but also SOX4 suppressed apoptosis, indicating that multiple anti-apoptotic pathways underlie cooperative leukemogenesis by HOXA9 and MYC. These results demonstrate that HOXA9 is a crucial transcriptional maintenance factor that promotes MYC-mediated leukemogenesis, potentially explaining why HOXA9 is highly expressed in many leukemias.<br />Competing Interests: RM, AK, HO, YK, ST, HM, TI No competing interests declared, AY received a research grant from Dainippon Sumitomo Pharma Co. Ltd.<br /> (© 2021, Miyamoto et al.)
- Subjects :
- Animals
Carcinogenesis genetics
Female
Gene Expression Regulation, Leukemic
HEK293 Cells
Homeodomain Proteins genetics
Humans
Leukemia, Myeloid metabolism
Mice
Mice, Inbred C57BL
Myeloid-Lymphoid Leukemia Protein genetics
Proto-Oncogene Proteins c-bcl-2 genetics
Proto-Oncogene Proteins c-bcl-2 metabolism
SOXC Transcription Factors genetics
SOXC Transcription Factors metabolism
Cell Transformation, Neoplastic metabolism
Homeodomain Proteins metabolism
Neoplasm Proteins metabolism
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 34310280
- Full Text :
- https://doi.org/10.7554/eLife.64148