Variant complex translocations involving chromosomes 1, 9, 9, 15 and 17 in acute promyelocytic leukemia without RAR alpha/PML gene fusion rearrangement.

Acute promyelocytic leukemia (APL;M3) is specifically characterized by a predominance of malignant promyelocytes having atypical reciprocal translocation involving chromosome 15 and 17 [t(15;17)(q22;q11)] resulting in the fusion of retinoic acid receptor alpha (RAR alpha) on chromosome 17 and the putative transcription factor gene PML, ie the translocation generates two fusion transcripts, PML/RAR alpha and RAR alpha/PML. We describe a patient with clinical and morphologic characteristics of atypical APL but with a previously undescribed variant translocation. A 35-year-old Hispanic having atypical APL was referred for cytogenetic evaluation. The cytogenetic findings with GTG-banding coupled with FISH analysis revealed the following karyotype: 46,XX,der(9)t(1;9)(q25;q34)der(9)t(9;?)(q34;?), t(15;17)(q22;q11)ish. der(9)t(1;9)(q25;q34)(WCP1+,WCP9+),t(9;17;15)(q34;q11;q22) (WCP9+,WCP15+,PML+;WCP17+,RAR alpha +;WCP15+,WCP17+,PML-)[20]/46,XX[5]. The chromosome 17q was translocated to the chromosome 15q. However, chromosome 15q including the PML gene normally translocating to 17q and creating the RAR alpha/PML fusion gene, translocated to chromosome 9q. Does this patient have another subset of APL? Or is the genetics of APL different in cases with variant translocations as opposed to those with atypical t(15;17) translocation, though in the majority of the cases their clinical presentation remains the same.