Frequent Homozygous Deletions of D13S218 on 13q14 in B-Cell Chronic Lymphocytic Leukemia Independent of Disease Stage and Retinoblastoma Gene Inactivation

A correlative study has been performed to delineate further the role of the Rb gene in the disease B-cell chronic lymphocytic leukemia (B-CLL). First, we examined DNAs from B cells from 140 B-CLL patients representing all Rai stages of disease for the loss of 13q14 using two microsatellite markers mapping distal to the Rb locus. Loss of heterozygosity (LOH) of D13S133 was infrequent, occurring in 5 of 140 (4%) patients. The frequency for LOH of D13S218 was 33 of 140 (24%) samples and was independent of Rai stage of disease. Rb protein was detected in 19 of 23 (83%) samples. Of 4 patients lacking detectable Rb gene expression, only one showed LOH of D13S218 . Rb protein levels varied from undetectable to high in samples with or without LOH for D13S218 , and the levels were also independent of Rai stage of disease. Our findings support the role of DBM on 13q14, rather than Rb , as the candidate tumor suppressor gene that is frequently targeted for deletion in B-CLL. In addition, the data suggest that other mechanism(s) contribute to altered Rb expression detected in one-fourth of B-CLL B-cells.