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CM Morris, N Heisterkamp, MA Kennedy, PH Fitzgerald and J Groffen
Department of Pathology, Children's Hospital of Los Angeles, CA.
Leukemic 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 isolated from genomic DNA 5' of the
junction showed that 3' M-BCR was joined to a region of chromosome 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 chromosome 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;q11) but left the
chromosome 9 insert, including 3' ABL, in chromosome 22.
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