title: Therapy-related acute myeloid leukemia in a child with Noonan syndrome and clonal duplication of the germline PTPN11 mutation.
abstract: 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.
authors.affiliation: Department of Pediatric Hematology-Oncology, St-Luc University Hospital, Catholic University of Louvain, Brussels, Belgium. christophe.chantrain@pedi.ucl.ac.be
authors.forename: Christophe F
authors.initials: CF
authors.lastname: Chantrain
authors.forename: Priscilla
authors.initials: P
authors.lastname: Jijon
authors.forename: Thomas
authors.initials: T
authors.lastname: De Raedt
authors.forename: Christiane
authors.initials: C
authors.lastname: Vermylen
authors.forename: Hélène A
authors.initials: HA
authors.lastname: Poirel
authors.forename: Eric
authors.initials: E
authors.lastname: Legius
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Brichard
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002675:Child, Preschool; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7; D017809:Fatal Outcome; D005260:Female; D020440:Gene Duplication / Q000187:drug effects*; D018095:Germ-Line Mutation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced* / Q000235:genetics* / Q000628:therapy; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000139:chemically induced* / Q000235:genetics* / Q000628:therapy; D009634:Noonan Syndrome / Q000150:complications / Q000235:genetics / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012175:Retinoblastoma / Q000188:drug therapy / Q000235:genetics; D014182:Transplantation, Autologous
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases