Clinical and genetic features of therapy-related myeloid neoplasms after chemotherapy for acute promyelocytic leukemia.
Acute promyelocytic leukemia (APL) is a highly curable disease with excellent complete remission and long-term survival rates. However, the development of therapy-related myeloid neoplasms (t-MN) is being reported with increasing frequency in patients successfully treated for APL. We attempted to clarify the different clinical features and hematologic findings between t-MN and relapse cases, and to identify gene alterations involved in t-MN. We compared 10 relapse and 11 t-MN cases that developed in 108 patients during their first complete remission from APL. At APL diagnosis, t-MN patients had lower white blood cell counts than did relapse patients (P = .048). Overall survival starting from chemotherapy was significantly worse in t-MN patients than in relapse patients (P = .022). The t-MN cases were characterized as CD34(+)/HLA-DR(+) and PML-RARA(-), and 4 RUNX1/AML1 mutations were detected. T-MN is easily distinguished from APL relapse by evaluating these hematologic features, and it may originate from primitive myeloid cells by chemotherapy-induced RUNX1 mutations.
Imagawa
Jun
J
Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Harada
Yuka
Y
Shimomura
Takeshi
T
Tanaka
Hideo
H
Okikawa
Yoshiko
Y
Hyodo
Hideo
H
Kimura
Akiro
A
Harada
Hironori
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D005260:Female; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3