The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease
Year: 2005
Type: article
Study design: Observational Study
Abstract: Germ line PTPN11 mutations cause 50% of cases of Noonan syndrome (NS). Somatic mutations in PTPN11 occur in 35% of patients with de novo, nonsyndromic juvenile myelomonocytic leukemia (JMML). Myeloproliferative disorders (MPDs), either transient or more fulminant forms, can also occur in infants with NS (NS/MPD). We identified PTPN11 mutations in blood or bone marrow specimens from 77 newly reported patients with JMML (n = 69) or NS/MPD (n = 8). Together with previous reports, we compared the spectrum of PTPN11 mutations in 3 groups: (1) patients with JMML (n = 107); (2) patients with NS/MPD (n = 19); and (3) patients with NS (n = 243). Glu76 was the most commonly affected residue in JMML (n = 45), with the Glu76Lys alteration (n = 29) being most frequent. Eight of 19 patients with NS/MPD carried the Thr73Ile substitution. These data suggest that there is a genotype/phenotype correlation in the spectrum of PTPN11 mutations found in patients with JMML, NS/MPD, and NS. This supports the need to characterize the spectrum of hematologic abnormalities in individuals with NS and to better define the impact of the PTPN11 lesion on the disease course in patients with NS/MPD and JMML.
Source: Blood
Author: C. P. Kratz
Institution: University of California, San Francisco
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: Leukemia and Lymphoma Society, Aarhus Universitet, Frank A. Campini Foundation, Leuka, Cancer Research Coordinating Committee, Albert-Ludwigs-Universität Freiburg, Hacettepe Üniversitesi, National Institutes of Health, Comprehensive Cancer Center, University of Alabama at Birmingham, National Heart, Lung, and Blood Institute, National Cancer Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1223547530, SCCOR in Pediatric Heart Development and Disease, G2082995753, G2139049212, Disease pathogenesis of Noonan syndrome and related disorders, G390041114, North American Juvenile Myelomonocytic Leukemia Project, G4943586465, Molecular Basis of Noonan Syndrome and Related Disorder, LEUKEMIA THERAPY BASED ON ABNORMAL SIGNAL TRANSDUCTION, G7260098912, Role of PTPN11 Mutations in Myeloid Leukemogenesis, G9000132054, Cancer Center Support Grant
OpenAlex ID: W2129901774