Late-appearing PML/RAR alpha fusion transcript with coincidental t(12;13)(p13.2;q14) in acute promyelocytic leukemia lacking the t(15;17) cytogeneticanomaly

The late appearance of a cytogenetic/molecular hallmark in human leukemias is a rare event. We report on a case of acute myeloid leukemia with morphol ogy, immunophenotype and clinical features typical of promyelocytic subtype (APL), in which the specific PML/RAR alpha gene rearrangement was molecula rly detected only at second relapse of disease, without cytogenetic evidenc e of the t(15;17). The emergence of the PML/RAR alpha gene may be therapy-r elated or may represent the exceptional result of a clonal evolution during progression of neoplasia. At second relapse, a novel cell clone bearing a t(12;13)(p13.2;q14) was also observed and a molecular deletion and rearrang ement of a locus at 13q14, distinct from retinoblastoma (Rb1) locus, was fo und. In this unusual case, the PML/RAR alpha product seems to be not essent ial for the expression of the promyelocytic phenotype at diagnosis and, whe n detectable, it is not the sole genetic defect. (C) 2000 Elsevier Science Inc. All rights reserved.