MYELODYSPLASTIC SYNDROME TRANSFORMING TO ACUTE PROMYELOCYTIC-LIKE LEUKEMIA WITH TRISOMY AND REARRANGEMENT OF CHROMOSOME-II

Variants of the t(15;17)(q22;q12-q21) chromosomal rearrangement associ ated with acute promyelocytic leukemia (APL) have been previously desc ribed and they frequently involve either chromosome 15 and/or 17. Prev iously we reported a rare variant t(11;17). We now describe two patien ts with myelodysplastic syndrome (MDS) that transformed to APL-like le ukemia. Both had trisomy 11 at the diagnosis of APL-like leukemia. Fol lowing treatment for APL, patient 1 reverted to MDS and showed a norma l karyotype. When leukemia recurred, his bone marrow karyotype was 47, XY,t(4;11),+11,der(22)t(1;22). Both patients were treated with all-tra ns retinoic acid (ATRA) for APL for 5 weeks, but failed to respond. Th e karyotype of patient 1 after ATRA treatment was 46,XY,t(4;11); the t risomy 11 had been lost and the bone marrow was replaced with immature myeloblasts without promyelocytes. In patient 2, the karyotype remain ed the same as at diagnosis, i.e., 47,X,-Y,dir ins(4;7),de1(5),+ 6,de1 (7),+ 8,+ 11,-18. Molecular analysis by reverse transcriptase PCR anal ysis showed the presence of wild type retinoic acid receptor alpha (RA RA) and the absence of the PML-RARA chimeric gene associated with t(15 ;17). Additional analysis of PLZF, a new zinc finger gene associated w ith t(11;17), also showed the absence of this hybrid gene. These data support the concept that APL is a heterogeneous disorder and that vari ants with chromosome 11 rearrangement exist that do not respond to ATR A. (C) 1994 Wiley-Liss, Inc.