Confirmation of Rb gene defects in B-CLL clones and evidence for variable predominance of the Rb defective cells within the CLL clone.
In 70 B-CLL patients, deletion or translocation, at or near the retinoblastoma (Rb) site, was detected in 20 by cytogenetic analysis. Purified B cell clones from 13 of these B-CLL patients were isolated and studied for Rb gene status, Rb mRNA and the Rb protein product. Southern blot analysis of the Rb site detected internal deletions (N = 1) or a single allele loss (N = 2) in five patients. Northern blots detected reduced Rb mRNA in four patients. Immunoblot of whole cell lysate revealed reduced levels of unphosphorylated Rb protein in six CLL patients. No CLL B cell clone contained phosphorylated Rb species. These molecular studies have confirmed the cytogenetic alteration of 13q12-14 sites in B-CLL cells. In addition, cytogenetic and molecular biologic analysis suggest heterogeneity in the B cell clone for Rb gene abnormality. B-CLL patients with abnormalities in both cytogenetic and Rb DNA/RNA analysis will have a dominance of B cells with an Rb abnormality (N = 5). In patients whose Rb defective CLL cells constitute only a minor subpopulation of the total B cell clone, only cytogenetic defects would likely be detected (N = 7).
Kay
N E
NE
Department of Medicine, Minneapolis Veterans Affairs Medical Center, Minnesota.
Suen
R
R
Ranheim
E
E
Peterson
L C
LC
D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D002999:Clone Cells; D017353:Gene Deletion; D016161:Genes, Retinoblastoma / Q000235:genetics*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D016160:Retinoblastoma Protein / Q000032:analysis; D014178:Translocation, Genetic
D012333:RNA, Messenger; D016160:Retinoblastoma Protein