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Therapy-related acute myeloid leukemia in a child with Noonan syndrome and clonal duplication of the germline PTPN11 mutation.

Chantrain CF, Jijon P, De Raedt T, Vermylen C, Poirel HA, Legius E, Brichard B

Department of Pediatric Hematology�Oncology, St�Luc University Hospital, Catholic University of Louvain, Brussels, Belgium.

A 4-year-old girl with Noonan syndrome (NS) and constitutive PTPN11 mutation presented with stage 4 neuroblastoma and was treated by intensive chemotherapy. During the treatment, cytogenetic analysis revealed the development of a hyperdiploid clone with duplication of the germline PTPN11 mutation in a morphologically normal bone marrow. A few months later, the patient developed acute myelomonoblastic leukemia with an additional clonal deletion of 7q. Although, we cannot conclude whether there is an association between NS and neuroblastoma, this case suggests that duplication of germline PTPN11 mutations, potentially induced by chemotherapy, contributes to leukemogenesis in patients with NS. (c) 2005 Wiley-Liss, Inc.

Published 3 August 2005 in Pediatr Blood Cancer.
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