Abstract
We report here that individuals with Noonan syndrome and juvenile myelomonocytic leukemia (JMML) have germline mutations in PTPN11 and that somatic mutations in PTPN11 account for 34% of non-syndromic JMML. Furthermore, we found mutations in PTPN11 in a small percentage of individuals with myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML). Functional analyses documented that the two most common mutations in PTPN11 associated with JMML caused a gain of function.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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COS Cells
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Child
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Humans
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Intracellular Signaling Peptides and Proteins
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Leukemia, Myeloid, Acute / enzymology*
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Leukemia, Myeloid, Acute / genetics*
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Leukemia, Myelomonocytic, Acute / complications
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Leukemia, Myelomonocytic, Acute / enzymology*
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Leukemia, Myelomonocytic, Acute / genetics*
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Mutation*
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Myelodysplastic Syndromes / enzymology*
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Myelodysplastic Syndromes / genetics*
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Noonan Syndrome / complications
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Noonan Syndrome / enzymology
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Noonan Syndrome / genetics
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatases / genetics*
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Protein Tyrosine Phosphatases / metabolism
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Transfection
Substances
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Intracellular Signaling Peptides and Proteins
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PTPN11 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatases