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Morphologic, Cytogenetic, and Molecular Abnormalities in Therapy-Related Acute Promyelocytic Leukemia

C. Cameron Yin MD, PhD, Armand B. Glassman MD, Pei Lin MD, Jose R. Valbuena MD, Dan Jones MD, PhD, Rajyalakshmi Luthra PhD, L. Jeffrey Medeiros MD
DOI: http://dx.doi.org/10.1309/TJFFK819RPCLFKJ0 840-848 First published online: 1 June 2005


We describe 17 cases of therapy-related acute promyelocytic leukemia (tAPL). Treatment for the initial neoplasms (mostly carcinomas and non-Hodgkin lymphomas) included radiation and chemotherapy in 11 patients, radiation in 3, and chemotherapy in 3. The interval between the initial neoplasm and tAPL ranged from 17 to 116 months (median, 40 months). Morphologically, all 13 cases with available bone marrow aspirate smears showed tAPL. Dyserythropoiesis or dysmegakaryopoiesis was identified in 11 cases. In 2 cases, too few nonneoplastic cells and, in all cases, too few maturing granulocytes were present to assess for dysplasia. Conventional cytogenetics or fluorescence in situ hybridization (FISH) showed the t(15;17)(q22;q21) in all cases; 6 as a sole abnormality, 9 with additional abnormalities, and 2 assessed only by FISH. Reverse transcription–polymerase chain reaction (PCR) studies showed PML/RARα in 13 cases (8 short form, 5 long form). Mutations of the flt3 gene were detected by PCR in 5 (42%) of 12 cases. We conclude that dysplastic features, secondary cytogenetic abnormalities, and flt3 mutations are common in tAPL.

Key Words:
  • Acute promyelocytic leukemia
  • APL
  • Therapy-related
  • Dysplasia
  • Cytogenetic abnormalities
  • PML/RARα
  • flt3