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.

Abstract

BACKGROUND:

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).

PATIENTS AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: L Hoffmann, P Möller, J Pedersen-Bjergaard, A Waage, M Pedersen, F R Hirsch (Affiliation: Laboratory for Cancer Genetics and Cytogenetics, Finsen Center, Rigshospitalet, Copenhagen, Denmark.)
• Journal: Annals 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
• PMID: 8589015 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Topoisomerase II Inhibitors

Topics

• 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