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 |
Transduction of the PTPN11 mutation into JMML iPSCs with the wild-type of both genes increased CD34<sup>+</sup> cell production to a level comparable to that obtained with JMML iPSC colonies harbouring the two genetic mutations.
|
31222725 |
2019 |
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We used patient-derived induced pluripotent stem cells (iPSCs) to characterize the signaling profiles and potential therapeutic vulnerabilities of PTPN11-mutant and CBL-mutant JMML.
|
29884903 |
2019 |
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 |
Biomarker
|
disease |
BEFREE |
At least one protein phosphatase, PTPN11, has emerged as a critical driver of this process in juvenile myelomonocytic leukemia.
|
30026077 |
2019 |
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Animal models of mutant Ptpn11 have probed the signaling pathways that contribute to JMML.
|
29774106 |
2018 |
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 |
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 |
Somatic mutation E76K in SHP2 is the most commonly identified mutation found in up to 35% of patients with JMML.
|
30129165 |
2018 |
Juvenile Myelomonocytic Leukemia
|
1.000 |
CausalMutation
|
disease |
CLINVAR |
Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains.
|
28628100 |
2017 |
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We present the case of a child with JMML in the setting of germline PTPN11 mutation and Noonan syndrome with suspected secondary development of monosomy 7 in the bone marrow.
|
28084675 |
2017 |
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 |
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 |
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 |
Unraveling the genetics of JMML has demonstrated that JMML in patients with germ line PTPN11 and CBL mutations often regresses spontaneously, and therapy is seldom indicated.
|
27913534 |
2016 |
Juvenile Myelomonocytic Leukemia
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
Previous studies have demonstrated that mutations in Ptpn11 induce a JMML-like MPN through cell-autonomous mechanisms that are dependent on Shp2 catalytic activity.
|
27783593 |
2016 |
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
UNIPROT |
Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling.
|
26742426 |
2016 |
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Here, we report that hematopoietic cells differentiated from human induced pluripotent stem cells (hiPSCs) harboring NS/JMML-causing PTPN11 mutations recapitulated JMML features. hiPSC-derived NS/JMML myeloid cells exhibited increased signaling through STAT5 and upregulation of miR-223 and miR-15a.
|
26456833 |
2015 |
Juvenile Myelomonocytic Leukemia
|
1.000 |
Biomarker
|
disease |
BEFREE |
Nonsyndromic Juvenile Myelomonocytic Leukemia With PTPN11 Mutation in a 9-Year-old Girl.
|
26181421 |
2015 |
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
This report describes a juvenile myelomonocytic leukemia (JMML) case with a typical PTPN11 mutation (p.E76K) at different allele frequencies in the bone marrow mononuclear cells, buccal smear cells, and fingernails at diagnosis, which was suggestive of PTPN11 somatic mosaicism; however, the PTPN11 mutation in the buccal smear cells and fingernails was lost after unrelated cord blood transplantation.
|
26440969 |
2015 |
Juvenile Myelomonocytic Leukemia
|
1.000 |
Biomarker
|
disease |
CTD_human |
The genomic landscape of juvenile myelomonocytic leukemia.
|
26457647 |
2015 |
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 |
CausalMutation
|
disease |
CLINVAR |
Mechanism and treatment for learning and memory deficits in mouse models of Noonan syndrome.
|
25383899 |
2014 |
Juvenile Myelomonocytic Leukemia
|
1.000 |
Biomarker
|
disease |
BEFREE |
Following estimation of hypersensitivity to GM-CSF and genetic analysis of PTPN11, he was diagnosed with JMML in the blast crisis phase.
|
25047104 |
2014 |
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 |