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Molecular studies of chronic myelogenous leukemia using the polymerase chain reaction
Author(s) -
Nakamura Kozue,
Miyashita Toshiyuki,
Ozaki Miwako,
Iwaya Makoto,
Nakazawa Shinpei,
Okamura Jun,
Kamada Nanao,
Tanaka Kimio,
Kobayashi Noboru,
Mizutani Shuki
Publication year - 1991
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19911201)68:11<2426::aid-cncr2820681117>3.0.co;2-c
Subject(s) - breakpoint cluster region , chronic myelogenous leukemia , breakpoint , philadelphia chromosome , exon , abl , microbiology and biotechnology , biology , messenger rna , chromosome , leukemia , chromosomal translocation , genetics , gene , receptor , tyrosine kinase
Thirty‐two cases of chronic myelogenous leukemia (CML) were studied to determine whether there was a correlation between the position of the chromosome breakpoint within the breakpoint cluster region (bcr) on chromosome 22 and the type of chimeric mRNA expression. One case with the chromosome breakpoint in zone 2 of the major bcr (Mbcr) and six cases with breakpoints in zone 3 expressed Mbcr exon 2‐abl (b2‐a) mRNA, and they were in distinguishable at the level of mRNA expression. The remaining ten cases with breakpoints in zone 3 and all ten cases with breakpoints in zone 4 expressed Mbcr exon 3‐abl (b3‐a) mRNA with or without b2‐a mRNA. Three cases with breakpoints in zone 5 expressed b3‐a mRNA, and none of these expressed Mbcr exon 4‐abl(b4‐a) mRNA. The cases with breakpoints in zones 4 or 5 had b3‐a mRNA expression indistinguishable from those with breakpoints in zone 3. In two patients, the breakpoint in the bcr could not be determined by Southern hybridization using the 3 bcr probe or the large bcr probe. However, when analyzed for chimeric mRNA expression, both of them exhibited b3‐a chimeric mRNA, suggesting the possibility that the entire Mbcr is deleted in the majority of leukemic cells in these patients. These studies indicate that Southern hybridization analysis combined with the polymerase chain reaction assay is a useful approach to understanding the pathologic role of bcr‐abl gene recombination and expression in the development of CML. 68:2426‐2430, 1991.