Therapy-related acute promyelocytic leukemia with t(15;17) (q22;q12) following chemotherapy with drugs targeting DNA topoisomerase II. A report of two cases and a review of the literature.

The development of therapy-related acute myeloid leukemia (t-AML) with balanced translocations to chromosome bands 11q23 and 21q22 has recently been significantly related to previous treatment with several cytostatic drugs poisoning DNA topoisomerase II. A similar association was suspected for other balanced chromosomal aberrations such as the t(15;17) characteristic of acute promyelocytic leukemia (APL).
Two cases of acute promyelocytic leukemia were observed following treatment for seminoma with etoposide, cisplatin, and bleomycin and treatment for breast cancer with 4-epi-doxorubicin and subsequent cyclophosphamide, methotrexate, and 5-fluorouracil followed by radiotherapy. Both cases presented a t(15;17) (q22;q12) and were examined for the characteristic chimeric rearrangement of the RAR alpha and PML genes observed in acute promyelocytic leukemia de-novo.
In both cases the characteristic chimeric rearrangement was demonstrated. Case no. 2 in addition to the t(15;17) showed an inversion of the long arm of a chromosome no. 5 and a del(7)(q22) in all abnormal mitoses studied. Despite these findings the patient obtained a complete morphological and cytogenetic remission of the leukemia following treatment with all-trans-retinoic acid.
Based on these two cases and a review of the literature it is concluded that the development of t-APL with the balanced translocation t(15;17) is related to previous treatment with cytostatic drugs targeting DNA topoisomerase II and that additional abnormalities of the long arms of chromosomes no. 5 and no. 7 do not interfere with the induction of remission with all-trans-retinoic acid.
AuthorsL Hoffmann, P Möller, J Pedersen-Bjergaard, A Waage, M Pedersen, F R Hirsch
JournalAnnals of oncology : official journal of the European Society for Medical Oncology / ESMO (Ann Oncol) Vol. 6 Issue 8 Pg. 781-8 (Oct 1995) ISSN: 0923-7534 [Print] NETHERLANDS
PMID8589015 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Topoisomerase II Inhibitors
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols (adverse effects)
  • Base Sequence
  • Breast Neoplasms (drug therapy)
  • Female
  • Humans
  • Leukemia, Promyelocytic, Acute (enzymology, etiology, genetics)
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Neoplasms, Second Primary (enzymology, etiology, genetics)
  • Seminoma (drug therapy)
  • Testicular Neoplasms (drug therapy)
  • Topoisomerase II Inhibitors
  • Translocation, Genetic

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