PH-NEGATIVE CHRONIC MYELOID-LEUKEMIA - MOLECULAR ANALYSIS OF ABL INSERTION INTO M-BCR ON CHROMOSOME-22

Google Scholar
  • 1 November 1990
    • journal article
    • research article
    • Vol. 76  (9) , 1812-1818
Abstract
Leumemic cells from a patient with Ph-negative chronic myeloid leukemia (CML) had a normal karyotype. M-BCR was rearranged and chromosome in situ hybridization showed an ABL insertion between 5'' and 3'' M-BCR on an apparently normal chromosome 22. The association of 5'' BCR and 3'' ABL at the 5'' junction of the chromosome 9 insert was typical of that found for the BCR-ABL fusion gene in other patients with the standard t(9;22) and CML. With an M-bcr-3'' probe, we cloned and characterized a 3'' junction fragment. Field inversion gel electrophoresis and chromosome in situ hybridization studies using a probe isolation from genomic DNA 5'' of the junction showed that 3'' M-BCR was joined to a region of chromsome 9q34 rich in repetitive sequences and lying some distance 3'' of ABL. The chromosome 9 insert was at least 329 kilobases long and included 3'' ABL and a larger portion of chromsome 9q34. Our results allowed us to exclude transposon- or retroviral-mediated insertion of ABL into chromosome 22. Instead, we favored a two-translocation model in which a second translocation reconstituted a standard t(9;22)(q34;qII) but left the chromosome 9 insert, including 3'' ABL, in chromosome 22.