REARRANGEMENTS OF THE RETINOIC ACID RECEPTOR-ALPHA AND PROMYELOCYTIC LEUKEMIA ZINC-FINGER GENES RESULTING FROM T(11 17)(Q23 Q21) IN A PATIENT WITH ACUTE PROMYELOCYTIC LEUKEMIA

Cytogenetic study of a patient with acute promyelocytic leukemia (APL) showed an unusual karyotype 46,xy,t(11;17) (q23;21) without apparent rearrangement of chromosome 15. Molecular studies showed rearrangement s of the retinoic acid receptor alpha (RARalpha) gene but no rearrange ment of the promyelocytic leukemia gene consistent with the cytogeneti c data. Similar to t(15;17) APL, all-trans retinoic acid treatment in this patient produced an early leukocytosis which was followed by a my eloid maturation, but the patient died too early to achieve remission. Further molecular analysis of this patient showed a rearrangement bet ween the RARalpha gene and a newly discovered zinc finger gene Flamed PLZF (promyelocytic leukemia zinc finger). The fusion PLZF-RARalpha ge ne found in this case, was not found in DNA obtained from the bone mar row of normals, APL with t(15;17) and in one patient with AML-M2 with a t(11;17). Fluorescence in situ hybridization using a PLZF specific p robe localized the PLZF gene to chromosomal band 11q23.1. Partial exon /intron structure of the PLZF gene flanking the break point on chromo some 11 was also established and the breakpoint within the RARalpha ge ne was mapped approximately 2 kb downstream of the exon encoding the 5 ' untranslated region and the unique A2 domain of the RARalpha 2 isofo rm.