RARA and PML gene rearrangements in acute promyelocytic leukemia with complex translocations and atypical features.

The translocation t(15;17) associated with acute promyelocytic leukemia (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 cytogenetic translocations and five cases with atypical phenotypic features with rearrangements within or adjacent to the second intron of the RARA gene. Two patients demonstrated three-way translocations involving chromosomes 3, 15, and 17, but with differing breakpoints on the short arm of chromosome 3. A third patient developed a complex karyotype at the time of third relapse, but with no change in RARA and PML gene rearrangement 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 receptor beta and gamma gene rearrangements. The localization of breakpoints to the second intron of the RARA gene in cytogenetically and phenotypically atypical cases provides additional support for a requisite role of the PML/RARA fusion gene in the pathogenesis of APL.