Complex 8;21 Chromosome Translocations formed by Two Step Mechanism and Simple 8;21chromosome Translocation without AML1 Gene Involvement in Acute Myelocytic Leukemia

Abstract

As a result of reciprocal translocation between chromosomes 8 and 21, acute myelocyticleukemia (AML) cells contains chimeric gene of AML1 and MTG8/ETO and express fusion proteins. The AML1-MTG8/ETO chimeric gene is considered to have an important role in the pathogenesis of AML FABM2. Among AML M2 patients, about 3 -5% of the patients show complex translocation including chromosome 8;21 and third chromosome. We analyzed metaphases from seven AML M2 patients with complex 8;21 translocation by two color FISH using WCP probes, AML1 probe and several cosmid probes locating near AML1 and MTG 8/ETO locus. All of the 7 patients could show two step translocation (chromosome8-chromosome 21-third chromosome). Seven patients including two insertion 8;21 cases represented two step translocation for formation either between chromosome [der(8); 8q-] and third chromosome or between [der(8); 8q-]and [der(21); 21q+ ] chromosomes . These results suggest that there is at least two step mechanism for the formation of complex 8;21 translocation, following formation of standard 8;21 translocation and AML1-MTG8/ETO chimeric gene. Interestingly, 3 patients diagnosed as AML FABM4, AML M2 transformed from myelodysplastic syndrome (MDS) (MDS-AMLM2) and acute lymphocytic leukemia (ALL) who had t(8;21) translocation had breakpoints proximal of AML1 gene. Other 13hematological disease such as AML or acute lymphocytic leukemia (ALL) patients who had chromosome abnormalities at band 21q22 of chromosome 21, including t(16;21)in 3 patients, had breakpoint at telomeric region of AML1 . These results indicate that 21q22 chromosomal region has higher chromosome instability and is genetically extremely unstable.