RARA AND PML GENE REARRANGEMENTS IN ACUTE PROMYELOCYTIC LEUKEMIA WITHCOMPLEX TRANSLOCATIONS AND ATYPICAL FEATURES

The translocation t(15; 17) associated with acute promyelocytic leukem ia (APL) results in fusion of the retinoic acid receptor alpha (RARA) gene on chromosome 17 with the putative transcription factor gene, PML , on chromosome 15. We report three cases of APL with complex cytogene tic translocations and five cases with atypical phenotypic features wi th rearrangements within or adjacent to the second intron of the RARA gene. Two patients demonstrated three-way translocations involving chr omosomes 3, 15, and 17, but with differing breakpoints on the short ar m of chromosome 3. A third patient developed a complex karyotype at th e time of third relapse, but with no change in RARA and PML gene rearr angement pattern. Three patients had normal karyotypes; however, only small numbers of cells could be analyzed. One patient's leukemic cells expressed the T-cell-associated antigen CD2 and revealed T-cell recep tor beta and gamma gene rearrangements. The localization of breakpoint s to the second intron of the RARA gene in cytogenetically and phenoty pically atypical cases provides additional support for a requisite rol e of the PML/RARA fusion gene in the pathogenesis of APL. (C) 1994 Wil ey-Liss, Inc.