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Two faces of RUNX3 in myeloid transformation
- Source :
- Experimental Hematology. 97:14-20
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- RUNX3, a transcription factor, has been implicated as a tumor suppressor in various cancers, including hematological malignancies; however, recent studies revealed an oncogenic function of RUNX3 in the pathogenesis of myeloid malignancies, such as myelodysplastic syndrome and acute myeloid leukemia. In contrast to the high frequency of mutations in the RUNX1 gene, deletion of and loss-of-function mutations in RUNX3 are rarely detected in patients with hematopoietic malignancies. Although RUNX3 is expressed in normal hematopoietic stem and progenitor cells, its expression decreases with aging in humans. The loss of Runx3 did not result in the development of lethal hematological diseases in mice despite the expansion of myeloid cells. Therefore, RUNX3 does not appear to initiate the transformation of normal hematopoietic stem cells. However, the overexpression of RUNX3 inhibits the expression and transcriptional function of the RUNX1 gene, but activates the expression of key oncogenic pathways, such as MYC, resulting in the transformation of premalignant stem cells harboring a driver genetic mutation. We herein discuss the mechanisms by which RUNX3 is activated and how RUNX3 exerts oncogenic effects on the cellular function of and transcriptional program in premalignant stem cells to drive myeloid transformation.
- Subjects :
- 0301 basic medicine
Cancer Research
Myeloid
Biology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Genetics
medicine
Animals
Humans
Myeloid Cells
Progenitor cell
Molecular Biology
Gene
Transcription factor
Myeloid leukemia
Cell Biology
Hematology
digestive system diseases
Hematopoiesis
Gene Expression Regulation, Neoplastic
Haematopoiesis
Cell Transformation, Neoplastic
Core Binding Factor Alpha 3 Subunit
030104 developmental biology
medicine.anatomical_structure
RUNX1
chemistry
Leukemia, Myeloid
Myelodysplastic Syndromes
030220 oncology & carcinogenesis
Cancer research
Stem cell
Subjects
Details
- ISSN :
- 0301472X
- Volume :
- 97
- Database :
- OpenAIRE
- Journal :
- Experimental Hematology
- Accession number :
- edsair.doi.dedup.....dace9e6a735b260a657266214b4f55b1