Clinical and genetic features of therapy-related myeloid neoplasms after chemotherapy for acute promyelocytic leukemia

Blood. 2010 Dec 23;116(26):6018-22. doi: 10.1182/blood-2010-06-289389. Epub 2010 Sep 22.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • CCAAT-Enhancer-Binding Proteins / genetics
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Female
  • Genes, ras / genetics
  • Humans
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / genetics*
  • Leukemia, Promyelocytic, Acute / pathology
  • Male
  • Middle Aged
  • Mutation / genetics
  • Neoplasms, Second Primary / chemically induced*
  • Neoplasms, Second Primary / genetics*
  • Neoplasms, Second Primary / pathology
  • Prognosis
  • Risk Factors
  • Survival Rate
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics


  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • Core Binding Factor Alpha 2 Subunit
  • RUNX1 protein, human
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3