The Presence of Typical and Atypical BCR-ABL Fusion Genes in Leukocytes of Normal Individuals: Biologic Significance and Implications for the Assessment of Minimal Residual Disease

摘要: The number of genetic lesions necessary to generate leukemia in humans is unknown, but it possible that certain specific abnormalities, eg, fusion genes, known be associated with acute and chronic are produced relatively frequently human cells require other events occur before the becomes manifest. We investigated this possibility by studying peripheral blood leukocytes from normal individuals various hematopoietic cell lines for presence expression p210 p190 types BCR-ABL gene myeloid (CML) lymphoblastic leukemia. used two-step reverse transcriptase-polymerase chain reaction (RT-PCR) assays which batches 108 per sample were tested 40 replicate reactions. estimate assay 1.5 logs more sensitive than RT-PCR we use routinely assess minimal residual disease. transcripts configurations found circulating 12 16 healthy adults analyzed. Transcripts an e1a2 junction (p190 BCR-ABL) present 11 p210-type b2a2 and/or b3a2 junctions detected 4 individuals. same non-CML showed classical or aberrant mRNA 3 7 p190-type all origin (HL60, KG1, U937, Kasumi, Jurkat, JVM13, JVM25), whereas NIH3T3 murine fibroblast line was reproducibly negative these genes. These findings confirm extend previous reports on detection leukemia-associated genes suggest generated cells, only infrequently do acquire additional changes produce humans. Although there a small probability such innocent BCR-ABL–carrying conventional assays, they may source some sporadically positive tests patients long-term remission. © 1998 American Society Hematology.