Therapy-related acute promyelocytic leukemia with t(15;17) (q22;q12) following chemotherapy with drugs targeting DNA topoisomerase .2. A report of two cases and a review of the literature

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 de1(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.