Acute myeloid leukemia with t(8;21)(q22;q22.1)/RUNX1-RUNX1T1 and KIT Exon 8 mutation is associated with characteristic mastocytosis and dismal outcomes.
The t(15;17) which generates PML-RARα, t(8;21) that produces AML1-ETO, and t(9;22) which generates BCR-ABL are the three most frequently seen chromosomal translocations in myeloid leukemia.
This mouse model may be useful for analysing the pathogenesis of myeloid leukemias with RUNX1 overdose, especially to examine whether an extra-copy of RUNX1 by trisomy 21 is causally related to Down's syndrome-related acute megakaryoblastic leukemia (DS-AMKL).
Our results provide direct evidence that AML1-ETO is critical for causing myeloid leukemia, but one or more additional mutations are required for leukemogenesis.
Constitutive expression of Evi-1 in hematopoietic cells, which is caused by retroviral insertions or chromosomal translocations and inversions, is closely associated with myelogenous leukemias and myelodysplastic syndromes in mice and humans.
AML1, a gene on chromosome 21 encoding a transcription factor, is disrupted in the (8;21)(q22;q22) and (3;21)(q26;q22) chromosomal translocations associated with myelogenous leukemias; as a result, chimeric proteins AML1/ETO(MTG8) and AML1/Evi-1 are generated, respectively.
CBFA2 forms a fusion gene with ETO and MDS1/EVI1 in translocations in myeloid leukemia and with ETV6(TEL) in the t(12;21) common in childhood pre-B acute lymphoblastic leukemia.
The AML1 gene on chromosome 21 is disrupted in the (8;21)(q22;q22) and (3;21)(q26;q22) translocations associated with myelogenous leukemias and encodes a DNA-binding protein.
This translocation results in the fusion of TEL, a recently described ETS-like gene on 12p13, and AML1, which was shown to be involved in the formation of fusion genes with ETO and EVI1 in myeloid leukemias.