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.
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).


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.
Hoffmann
L
L
Laboratory for Cancer Genetics and Cytogenetics, Finsen Center, Rigshospitalet, Copenhagen, Denmark.
Möller
P
P
Pedersen-Bjergaard
J
J
Waage
A
A
Pedersen
M
M
Hirsch
F R
FR
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016609:Neoplasms, Second Primary / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D018239:Seminoma / Q000188:drug therapy*; D013736:Testicular Neoplasms / Q000188:drug therapy*; D059005:Topoisomerase II Inhibitors; D014178:Translocation, Genetic
D059005:Topoisomerase II Inhibitors