Different Molecular Consequences of the 1;19 Chromosomal Translocation in Childhood B - Cell Precursor Acute Lymphoblastic Leukemia

摘要: The prognostically important 1;19 chromosomal translocation can alter the E2A gene on chromosome 19p13 in childhood B-cell precursor acute lymphoblastic leukemia (ALL), leading to formation of a fusion (E2A-PBX1) that encodes hybrid transcription factor with oncogenic potential. It is not known whether this molecular alteration uniform consequence t(1;19) or restricted events within specific immunologic subtypes disease. Therefore, we studied leukemic cells from 25 cases ALL, without evidence cytoplasmic Ig mu heavy chains (cIg); 17 had by cytogenetic analysis. Leukemic cell DNA samples were analyzed Southern blotting detect alterations genomic locus; polymerase chain reaction assay was used identify expression chimeric E2A-pbx1 transcripts RNA; and immunoblotting anti-Pbx1 antibodies E2A- Pbx1 proteins. Of 11 cIg+ ALL t(1;19), 10 pbx1 identical junctions characteristic set E2A-Pbx1 Each these rearrangements, including one which detected. By contrast, none six t(1;19)-positive, cIg- rearranged restriction fragments, detectable transcripts, Typical proteins detected eight leukemias identified analysis, emphasizing increased sensitivity analysis for detection abnormality. We conclude breakpoints differ those translocation. Leukemias express oncoproteins such as Bcr-Abl have poor prognosis most studies. Thus, techniques genes their aberrant products should allow more timely appropriate treatment aggressive