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Acute promyelocytic leukemia (APL) represents a biologic and clinically well-defined subtype of acute nonlymphocytic leukemia with specific morphologic and karyotypic characteristics. Although secondary leukemia and myelodysplastic syndromes (MDS) are the most frequent secondary neoplasms following chemotherapy for acute leukemia, their development after complete remission in patients with APL is uncommon. We describe the clinical and genetic features of two APL patients who achieved CR after chemotherapy and all-trans retinoid acid treatment and subsequently developed a MDS. Therapy-related MDS karyotype changes such as abnormalities of chromosomes 5 and 7 were found in the cytogenetic analysis. Since TP53 alteration was detected in one case, possible implications of these findings in the onset of MDS are discussed.

Secondary leukemia and myelodysplastic syndromes have been reported in patients following treatment for a wide range of neoplastic disorders. However second malignancies after chemotherapy and/or irradiation for osteosarcoma are unusual. PROCEDURE: We report the case of a 15-year-old girl who developed a myelodysplastic syndrome with evolution to acute nonlymphocytic leukemia after treatment for osteosarcoma. Therapy-related acute leukemia karyotype findings such as abnormalities of chromosomes 5, 7, and 17 were found in the cytogenetic analysis. Moreover, using denaturing gradient gel electrophoresis and DNA sequencing, we detected the presence of a double germline mutation in exon 7 of the TP53 gene. CONCLUSION: This observation supports the possibility of a causal relationship between germline TP53 mutations and the development of secondary leukemia and myelodysplasia