Open AccessRole of AML1/Runx1 in the pathogenesis of hematological malignancies
Author(s) -
Kurokawa Mineo,
Hirai Hisamaru
Publication year - 2003
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2003.tb01364.x
Subject(s) - runx1 , haploinsufficiency , biology , chromosomal translocation , leukemia , haematopoiesis , gene , breakpoint , point mutation , genetics , fusion protein , cancer research , transcription factor , mutation , phenotype , stem cell , recombinant dna
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.