t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1.

TLDR

The t(8;21)(q22;q22) translocation is a frequent, non‑random chromosomal abnormality in acute myeloid leukemia of the M2 subtype. The study reports the cloning of a gene, AML1, on chromosome 21 that is rearranged in leukemic cells from t(8;21) AML patients. Sequencing of cDNA clones revealed a 250‑amino‑acid protein encoded by AML1. Breakpoints in AML1 were clustered in a limited region, often within the same intron, and Northern blotting showed distinct mRNA species—particularly a larger transcript overexpressed in leukemic cells—indicating AML1’s involvement in the neoplastic transformation of t(8;21) AML.

Abstract

The t(8;21)(q22;q22) translocation is a non-random chromosomal abnormality frequently found in patients with acute myeloid leukemia (AML) with maturation (M2 subtype). We report here the cloning of a gene, named AML1, on chromosome 21 that was found to be rearranged in the leukemic cell DNAs from t(8;21) AML patients. The breakpoints in 16 out of 21 patients were clustered within a limited region of AML1, and detailed analysis in 3 patients revealed that the breakpoints occurred in the same intron of the gene. Sequencing of cDNA clones identified a long open reading frame encoding a 250-amino acid protein. Northern blot analysis detected four constant mRNA species in t(8;21) leukemic and normal cells; the largest species was more abundant in the leukemic cells than in normal cells. In addition, two mRNA species limited to the leukemic cells were found. These findings indicate that the AML1 gene may be involved in neoplastic transformation of AML with the t(8;21) translocation.