Morphologic, cytogenetic, and molecular abnormalities in therapy-related acute promyelocytic leukemia.
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 166 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/RARa 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.
Yin
C Cameron
CC
Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, USA.
Glassman
Armand B
AB
Lin
Pei
P
Valbuena
Jose R
JR
Jones
Dan
D
Luthra
Rajyalakshmi
R
Medeiros
L Jeffrey
LJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D002869:Chromosome Aberrations; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000473:pathology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000627:therapeutic use; D051941:fms-Like Tyrosine Kinase 3
D000970:Antineoplastic Agents; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D014212:Tretinoin; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3