The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease

Christian P. Kratz, Charlotte M. Niemeyer, Robert P. Castleberry, Mualla Cetin, Eva Bergsträsser, Peter D. Emanuel, Henrik Hasle, Gabriela Kardos, Cornelia Klein, Seiji Kojima, Jan Stary, Monika Trebo, Marco Zecca, Bruce D. Gelb, Marco Tartaglia, Mignon L. Loh

Research output: Contribution to journalArticlepeer-review

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 Thr73lle 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.

Original languageEnglish
Pages (from-to)2183-2185
Number of pages3
JournalBlood
Volume106
Issue number6
DOIs
Publication statusPublished - Sep 15 2005

ASJC Scopus subject areas

  • Hematology

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