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

Christophe F Chantrain; Priscilla Jijon; Thomas De Raedt; Christiane Vermylen; Hélène A Poirel; Eric Legius; Bénédicte Brichard

doi:10.1002/pbc.20527

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

Pediatr Blood Cancer. 2007 Jan;48(1):101-4. doi: 10.1002/pbc.20527.

Authors

Christophe F Chantrain¹, Priscilla Jijon, Thomas De Raedt, Christiane Vermylen, Hélène A Poirel, Eric Legius, Bénédicte Brichard

Affiliation

¹ Department of Pediatric Hematology-Oncology, St-Luc University Hospital, Catholic University of Louvain, Brussels, Belgium. christophe.chantrain@pedi.ucl.ac.be

PMID: 16078230
DOI: 10.1002/pbc.20527

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.

Publication types

Case Reports

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / adverse effects*
Child, Preschool
Chromosome Deletion
Chromosomes, Human, Pair 7
Fatal Outcome
Female
Gene Duplication / drug effects*
Germ-Line Mutation*
Humans
Intracellular Signaling Peptides and Proteins / genetics*
Leukemia, Myeloid, Acute / chemically induced*
Leukemia, Myeloid, Acute / genetics*
Leukemia, Myeloid, Acute / therapy
Neoplasm Staging
Neoplasms, Second Primary / chemically induced*
Neoplasms, Second Primary / genetics*
Neoplasms, Second Primary / therapy
Noonan Syndrome* / complications
Noonan Syndrome* / genetics
Noonan Syndrome* / therapy
Peripheral Blood Stem Cell Transplantation / adverse effects
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatases / genetics*
Retinoblastoma / drug therapy
Retinoblastoma / genetics
Transplantation, Autologous

Substances

Intracellular Signaling Peptides and Proteins
PTPN11 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatases