|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We report the first case of LIP in a patient with juvenile myelomonocytic leukemia (JMML) who was found to have a novel germline mutation of unknown significance in additional sex combs-like-1 (ASXL1) gene and a pathogenic somatic mutation of protein tyrosine phosphatase, nonreceptor type 11 (PTPN11) gene at diagnosis.
|
29023302 |
2018 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The SHP2 is encoded by the PTPN11 gene, which is a nonreceptor (pY)-phosphatase and mutation causes JMML.
|
31244092 |
2019 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
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 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
This confirms previous findings indicating that individuals with NS with specific mutations in PTPN11 are at risk of developing JMML.
|
15723289 |
2005 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Other mutations of putative pathogenetic relevance in MPDs include: JAK2V617F in PV, ET, and PMF; JAK2 exon 12 mutations in PV; MPLW515L/K in PMF and ET; KITD816V in SM; FIP1L1-PDGFRA in CEL-SM; rearrangements of PDGFRB in CEL-CMML and FGFR1 in stem cell leukemia-lymphoma syndrome; and RAS/PTPN11/NF1 mutations in JMML.
|
17351342 |
2007 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Juvenile Myelomonocytic Leukemia (JMML) is a relentlessly progressive myeloproliferative/myelodysplastic (MPD/MDS) hematopoietic disorder more common in patients with any one of at least three distinct genetic lesions, specifically NF1 gene loss and PTPN11 and NRAS mutations.
|
21681782 |
2011 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Given the strong association between monosomy 7 and mutation of genes involved in the RAS pathway in juvenile myelomonocytic leukemia, we also screened for pathogenetic variants in KRAS, NRAS, and PTPN11, but did not detect any changes.
|
20471511 |
2010 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The patients with JMML and neurofibromatosis (n = 2), the patient with lymphoma and t (8;13) positive AML, and a fourth patient with PTPN11 mutation did not remit and had unfavorable outcomes.
|
19798502 |
2010 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Collectively, this study reveals an important role of the Gab2/PI3K/mTOR pathway in mediating the pathogenic signaling of the PTPN11 gain-of-function mutations and a therapeutic potential of Rapamycin for PTPN11 mutation-associated JMML.
|
27840422 |
2017 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Although the risk of developing MPD/JMML could not be fully predicted by the underlying PTPN11 mutation, some germline PTPN11 mutations were preferentially associated with myeloproliferation: 10/48 patients with NS (20.8%) with a mutation in codon Asp61 developed MPD/JMML in infancy.
|
25097206 |
2014 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Resulting embryos show a direct relationship between a Noonan SHP-2 mutation and its ability to cause cardiac defects in Xenopus; embryos expressing Noonan SHP-2 mutations exhibit morphologically abnormal hearts, whereas those expressing an SHP-2 JMML-associated mutation do not.
|
22278918 |
2012 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
UNIPROT |
Functional analyses documented that the two most common mutations in PTPN11 associated with JMML caused a gain of function.
|
12717436 |
2003 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Gain-of-function variants in some RAS-MAPK pathway genes, including PTPN11 and NRAS, are associated with RASopathies and/or acquired hematological malignancies, most notably juvenile myelomonocytic leukemia (JMML).
|
28098151 |
2017 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
However, no mutations in the PTPN11, RAS, and CBL genes, or clinical features of neurofibromatosis type 1, which are associated with JMML, were detected.
|
22736231 |
2012 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
PTPN11 mutation with additional alterations showed significantly the poorest outcome in comparison with those with only one non-PTPN11 mutation, only one PTPN11 mutation, and combined mutations without PTPN11, respectively (P < 0.0001).Conclusion: Both PTPN11 mutation and the number of somatic alterations detected at diagnosis are likely to be the major determinant of outcome in JMML.
|
31807902 |
2020 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
RAS, NF1, and PTPN11 mutations are largely mutually exclusive in JMML, which suggests that mutant SHP-2 proteins deregulate myeloid growth through Ras.
|
14644997 |
2004 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Mutations in PTPN11, the gene encoding the protein tyrosine phosphatase Shp2, are common in juvenile myelomonocytic leukemia and induce hyperactivation of the phosphoinositide-3-kinase pathway.
|
22315502 |
2012 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
These data support the hypothesis that PTPN11 mutations induce hematopoietic progenitor hypersensitivity to GM-CSF due to hyperactivation of the Ras signaling axis and provide a basis for the GM-CSF signaling pathway as a target for rational drug design in JMML.
|
15644411 |
2005 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Such activating mutations of PTPN11 (human SHP-2 gene) were subsequently identified in individuals with Noonan syndrome, a human developmental disorder that is sometimes associated with juvenile myelomonocytic leukemia.
|
19622105 |
2009 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Chemical inhibition of TNK2 blocked MAPK signaling and colony formation in vitro and decreased disease burden in a patient with PTPN11-mutant JMML who was treated with the multikinase (including TNK2) inhibitor dasatinib.
|
30018082 |
2018 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
YS EMPs expressing mutant PTPN11 demonstrate functional and molecular features of JMML but do not cause disease following transplantation nor following unperturbed development.
|
28975680 |
2017 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Activating mutations in Shp2 are commonly associated with juvenile myelomonocytic leukemia but are not as well defined in other neoplasms.
|
25650089 |
2015 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We report a case of a dysmorphic neonate who presented with bilateral chylous effusions and juvenile myelomonocytic leukemia where NS was confirmed by the presence of PTPN11 mutation.
|
17414570 |
2007 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
A JMML-like myeloproliferative disorder has been described in about 30 neonates with NS and the PTPN11 mutation.
|
20029231 |
2009 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We report a female NS patient carrying a PTPN11 germline mutation c.417 G > C (p.E139D), who developed in her second year of life an acute lymphoblastic leukemia (ALL) and after remission, she developed at 4 years of age a juvenile myelomonocytic leukemia (JMML).
|
22315187 |
2012 |