leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Recently, a novel class of activating mutations in PTPN11 has been documented as a somatic event in a heterogeneous group of leukemias.
|
16631468 |
2006 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Given the association between NS and an increased risk of some malignancies, notably leukemia and probably some solid tumors including neuroblastoma (NB) and rhabdomyosarcoma (RMS), recent studies have reported that gain-of-function somatic mutations in PTPN11 occur in some hematological malignancies, especially de novo juvenile myelomonocytic leukemia (JMML) and in some solid tumors such as NB, although at a low frequency.
|
16518851 |
2006 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Here, we report that induction of the Ptpn11(E76K/+) mutation, the most common and active Ptpn11 mutation found in leukemias and solid tumors, in primary mouse embryonic fibroblasts resulted in proliferative arrest and premature senescence.
|
23884424 |
2013 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Synthetic lethality of TNK2 inhibition in PTPN11-mutant leukemia.
|
30018082 |
2018 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
LHGDN |
Our results document a strict correlation between the identity of the lesion and disease and demonstrate that NS-causative mutations have less potency for promoting SHP-2 gain of function than do leukemia-associated ones.
|
16358218 |
2006 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Leukemia-associated PTPN11 mutations were missense and were predicted to result in SHP-2 gain-of-function.
|
14982869 |
2004 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Effects of a leukemia-associated gain-of-function mutation of SHP-2 phosphatase on interleukin-3 signaling.
|
16371368 |
2006 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Gain-of-function (GOF) mutations of protein tyrosine phosphatase nonreceptor type 11 Ptpn11 (Shp2), a protein tyrosine phosphatase implicated in multiple cell signaling pathways, are associated with childhood leukemias and solid tumors.
|
26755576 |
2016 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Discovery of the new binding partners for disease-related SHP2 mutants might provide a fruitful foundation for developing strategies targeting Noonan-associated leukemia.
|
23584145 |
2013 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Here, we review recent information that has elucidated further the types and effects of PTPN11 defects in Noonan syndrome and compare them to the related, but specific, missense PTPN11 mutations causing other diseases including LEOPARD syndrome and leukemias.
|
16987887 |
2006 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
The human gene Ptpn11, which encodes the tyrosine phosphatase Shp2, may act as a proto-oncogene because dominantly activating mutations have been detected in several types of leukemia.
|
21575863 |
2011 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Activating mutations in PTPN11 (encoding SHP2), a protein tyrosine phosphatase (PTP) that plays an overall positive role in growth factor and cytokine signaling, are directly associated with the pathogenesis of Noonan syndrome and childhood leukemias.
|
23825065 |
2013 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
These results suggest that the pathogenesis of NS and leukemia is associated with enhanced phosphatase activity of mutant SHP-2.
|
15834506 |
2005 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Furthermore, somatic mutations of PTPN11 were found to be associated with pediatric leukemia.
|
19622105 |
2009 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Here we show that the interaction between leukemia-associated mutant Shp2 and Gab2, a scaffolding protein important for cytokine-induced PI3K/Akt signaling, was enhanced, and that the mTOR pathway was elevated in Ptpn11<sup>E76K/+</sup> leukemic cells.
|
27840422 |
2017 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Activating mutations of SHP2 have been associated with developmental pathologies such as Noonan syndrome and are found in multiple cancer types, including leukaemia, lung and breast cancer and neuroblastoma.
|
27362227 |
2016 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Genetic mutations in the phosphatase PTPN11 (SHP2) are associated with childhood leukemias.
|
30457860 |
2019 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
To elucidate the biochemical networks connecting the Kit mutant to leukemogenesis, in the present study, we performed a global profiling of tyrosine-phosphorylated proteins from mutant Kit-driven murine leukemia proerythroblasts and identified Shp2 and Stat5 as proximal effectors of Kit.
|
22438255 |
2012 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Certain germline and somatic PTPN11 mutations cause leukemias.
|
16399795 |
2006 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
LHGDN |
These results suggest that the pathogenesis of NS and leukemia is associated with enhanced phosphatase activity of mutant SHP-2.
|
15834506 |
2005 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Shp2 mutations might also contribute to the pathogenesis of some leukemias.
|
12826400 |
2003 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
She provides an overview of leukemias that are common in pediatric malignancies but rarely observed in adults, including the TEL-AML1 (ETV6-RUNX1) fusion associated with pediatric B-cell ALL, the OTT-MAL fusion associated with infant megakaryoblastic leukemia, PTPN11 mutations in juvenile myelomonocytic leukemia, and MLL fusion genes in leukemogenesis, among others.
|
15561678 |
2004 |
leukemia
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
We now know that at least one other PTP, the SH2 domain-containing phosphatase Shp2, is a bona fide oncogene that is mutated in several types of leukemia and hyperactivated by other mechanisms in some solid tumors.
|
17227708 |
2007 |
leukemia
|
0.400 |
Biomarker
|
disease |
BEFREE |
SHP2 has been shown to contribute to the progression of a number of cancer types including leukemia, gastric, and breast cancers.
|
29155585 |
2017 |
leukemia
|
0.400 |
Biomarker
|
disease |
BEFREE |
Our results document a strict correlation between the identity of the lesion and disease and demonstrate that NS-causative mutations have less potency for promoting SHP-2 gain of function than do leukemia-associated ones.
|
16358218 |
2006 |