Rearrangements in the second intron of the RARA gene are present in a large majority of patients with acute promyelocytic leukemia and are used as molecular marker for retinoic acid-induced leukemic cell differentiation

Chromosome 17 breakpoints in translocation t(15;17), a hallmark for acute promyelocytic leukemia (APL), have been shown to disrupt the retinoic acid receptor-alpha (RARA) gene. In this study, DNA probes around the second exon of the RARA gene showed rearrangements not previously detected. Analysis of 25 Chinese APL cases showed that RARA gene rearrangements were present in 23 cases (92%). The breakpoints were mapped unequivocally in 22 cases within the second intron of the gene. Therefore, the RARA gene rearrangement provides us with a specific marker of the disease. Simultaneous molecular and cytologic studies showed that the RARA gene rearrangements persisted during the first 2 to 3 weeks of all-trans retinoic acid (ATRA) therapy when differentiated granulocytes predominated in bone marrow, while these rearrangements disappeared after achieving complete remission. These data indicate that ATRA induces differentiation of APL cells.