Abstract:
:Abnormalities in structure and expression of the proto-oncogene c-abl have been implicated in the genesis of chronic myelogenous leukemia (CML). We studied leukemic cell DNA from 42 CML patients for evidence of rearrangement and/or amplification of c-abl analogous to that described in the CML cell line K562. Using the enzymes Bgl II, Pst I, Xba I, seven patients demonstrated an atypical Southern blot pattern similar to that found in K562. Analysis of DNA from normal controls and skin fibroblast from one of the seven patients established that the atypical blot pattern was due to a restriction fragment length polymorphism rather than a gene rearrangement. Further analysis revealed that c-abl exists as two alleles, A and B, yielding three genotypes: AA, AB and BB. Inheritance was Mendelian. With respect to allele A, allele B contains a deletion of about 1 kb lying in a intronic region in close proximity to highly repetitive Alu sequences and the sequence coding for phosphotyrosine of the c-abl protein. K562 and the seven patients with similar Southern patterns were identified as AB heterozygotes. In K562, only the A allele was amplified. The frequencies of AA and AB genotypes in 37 Caucasian CML patients were 81.1% and 18.9% and in 57 unrelated normal Caucasian controls 87.7% and 12.3%, not significantly different. The BB genotype was identified in less than 1% of Caucasians. Of note, five AB patients who developed a terminal blast crisis demonstrated a 4:1 lymphoid:myeloid crisis ratio in contrast to a 2:7 lymphoid:myeloid crisis ration in nine AA patients and a similar ratio in mixed AA and AB historical controls. Otherwise, CML patients with AA and AB genotypes manifested similar clinical parameters. No patients demonstrated amplification of c-abl and analysis of four AB patients for loss of one c-abl allele during the course of their disease was negative. Thus, amplification of c-abl and loss of one c-abl allele are both infrequent in CML and do not play a significant role in the course of the disease.
journal_name
Oncogenejournal_title
Oncogeneauthors
Daniel L,Ahmed CM,Bloodgood RS,Kidd JR,Castiglione CM,Duttagupta S,Lebowitz Psubject
Has Abstractpub_date
1987-05-01 00:00:00pages
193-200issue
2eissn
0950-9232issn
1476-5594journal_volume
1pub_type
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