Role of AML1/Runx1 in the pathogenesis of hematological malignancies

AML1/Runx1, originally identified as a gene located at the breakpoint of the t(8;21) translocation, encodes one of the two subunits forming a heterodimeric transcription factor. AML1 contains a highly evolutionally conserved domain called the Runt domain, responsible for both DNA binding and heterod...

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Bibliographic Details
Published in:Cancer science 2003-10, Vol.94 (10), p.841-846
Main Authors: Kurokawa, Mineo, Hirai, Hisamaru
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
AML1 protein
Animal models
Animals
Biological and medical sciences
Chromosome translocations
Core Binding Factor Alpha 2 Subunit
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Haploinsufficiency
Hematopoiesis
Humans
Leukemia
Leukemia - genetics
Leukemia - metabolism
Leukemia - pathology
MDS1 and EVI1 Complex Locus Protein
Medical sciences
Proto-Oncogene Proteins - chemistry
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Proto-Oncogenes
Review
Runx1 protein
Transcription Factors - chemistry
Transcription Factors - genetics
Transcription Factors - metabolism
Translocation, Genetic
Tumors
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Summary:AML1/Runx1, originally identified as a gene located at the breakpoint of the t(8;21) translocation, encodes one of the two subunits forming a heterodimeric transcription factor. AML1 contains a highly evolutionally conserved domain called the Runt domain, responsible for both DNA binding and heterodimerization with the partner protein, CBFβ. AML1 is widely expressed in all hematopoietic lineages, and regulates the expression of a variety of hematopoietic genes. Numerous studies have shown that AML is a critical regulator of hematopoietic development. In addition, AML1 and CBFβ are frequent targets for chromosomal translocation in human leukemia. Translocations lead to the generation of fusion proteins, which play a causative role for the development of leukemia, primarily by inhibiting AML1 function. Point mutations that impair AML1 function are also associated with familial and sporadic leukemias. Loss of AML1 function is thus implicated in a number of leukemias through multiple pathogenic mechanisms. However, AML1‐related translocations or haploinsufficiency of AML1 are not immediately leukemogenic in animal models, suggesting that additional genetic events are required for the development of full‐blown leukemia.
ISSN:1347-9032
1349-7006
DOI:10.1111/j.1349-7006.2003.tb01364.x