title: Myelodysplastic syndrome transforming to acute promyelocytic-like leukemia with trisomy and rearrangement of chromosome 11.
abstract: Variants of the t(15;17)(q22;q12-q21) chromosomal rearrangement associated with acute promyelocytic leukemia (APL) have been previously described and they frequently involve either chromosome 15 and/or 17. Previously we reported a rare variant t(11;17). We now describe two patients with myelodysplastic syndrome (MDS) that transformed to APL-like leukemia. Both had trisomy 11 at the diagnosis of APL-like leukemia. Following treatment for APL, patient 1 reverted to MDS and showed a normal 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-trans retinoic acid (ATRA) for APL for 5 weeks, but failed to respond. The karyotype of patient 1 after ATRA treatment was 46,XY,t(4;11); the trisomy 11 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),del(5), +6,del(7), +8, + 11,-18. Molecular analysis by reverse transcriptase PCR analysis showed the presence of wild type retinoic acid receptor alpha (RARA) 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(11;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 11 rearrangement exist that do not respond to ATRA.
authors.affiliation: Tumor Cytogenetics Laboratory, Polly Annenberg Levee Hematology Center, New York, New York.
authors.forename: V
authors.initials: V
authors.lastname: Najfeld
authors.forename: A
authors.initials: A
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Scalise
authors.forename: E P
authors.initials: EP
authors.lastname: Ambinder
authors.forename: G
authors.initials: G
authors.lastname: Fernandez
authors.forename: S
authors.initials: S
authors.lastname: Waxman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D005260:Female; D006801:Humans; D007621:Karyotyping; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000503:physiopathology; D014178:Translocation, Genetic; D014212:Tretinoin / Q000627:therapeutic use; D014314:Trisomy; D014407:Tumor Cells, Cultured
chemical_list: D014212:Tretinoin