The class II tumor-suppressor gene RARRES3 is expressed in B cell lymphocytic leukemias and down-regulated with disease progression

The molecular pathogenesis of B cell chronic lymphocytic leukemia (B-CLL), the most common form of leukemia, remains unknown. We have used the mRNA di fferential display technique to analyze genes that may be involved in the d evelopment/progression of B-CLL. We have identified the tumor suppressor re tinoic acid receptor responder 3 (RARRES3) as a B-CLL-related gene. RARRES3 maps to chromosome band 11q23, a region frequently deleted in lymphoprolif erative disorders. To assess the potential involvement of RARRES3 in leukem ogenesis, we examined 24 cases of B-CLL, 10 of acute lymphocytic leukemia ( ALL) and five related cell lines by RT-PCR and sequence analyses. We report a correlation between RARRES3 down-regulation and B-CLL progression. We al so found decreased RARRES3 gene levels in ALL cases and in the five cell li nes studied. We did not find mutations in any of the leukemia samples assay ed, including those with 11q23 deletion. These results indicate that RARRES 3 may play a role in B-CLL progression.