Variants of the t( 15; I7)(q22;q I2442 I ) chromosomal rearrangement associated with acute promyelocytic leukemia (APL) have been previously described and they frequently involve either chromosome I5 and/or 17. Previously we reported a rare variant t( I I ; 17). We now describe two patients with myelodysplastic syndrome (MDS) that transformed t o APL-like leukemia Both had trisomy I I at the diagnosis of APL-like leukemia Following treatment for APL, patient I reverted to MDS and showed a normal karyotype. When leukemia recurred, his bone marrow karyotype was 47.XY,t(4; I I), + I I ,der(22)t( I ;22). Both patients were treated with all-trans retinoic acid (ATRA) for APL for 5 weeks, but failed to respond. The karyotype of patient I after ATRA treatment was 46,XY,t(4;I I); the trisomy I I had been lost and the bone marrow was replaced with immature myeloblasts without promyelocytes. In patient 2. the karyotype remained the same as at diagnosis, i.e., 47,X,-Y,dir ins(4;7),de1(5), + 6,de1(7), + 8, + I I ,-18. Molecular analysis by reverse tranxriptase PCR analysis showed the presence of wild type retinoic acid receptor alpha (RAM) and the absence of the PML-RARA chimeric gene associated with t( 15; 17). Additional analysis of PLZF, a new zinc finger gene associated with t( I I ; 17). also showed the absence of this hybrid gene. These data support the concept that APL is a heterogeneous disorder and that variants with chromosome I I rearrangement exist that do not respond to ATRA. Genes Chrorn Cancer 1O:lS-25 (1994).