Emergence of secondary acute leukemia in a patient treated for osteosarcoma: implications of germline TP53 mutations.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
This observation supports the possibility of a causal relationship between germline TP53 mutations and the development of secondary leukemia and myelodysplasia.
Panizo
C
C
Department of Hematology, University Clinic of Navarra, School of Medicine, University of Navarra, Pamplona, Spain.
Patiño
A
A
Calasanz
M J
MJ
Rifón
J
J
Sierrasesumaga
L
L
Rocha
E
E
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D005260:Female; D005266:Femoral Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D016147:Genes, Tumor Suppressor / Q000187:drug effects / Q000235:genetics; D018095:Germ-Line Mutation / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000235:genetics*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery