|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Activation of the KIT tyrosine kinase by somatic mutation has been documented in a number of human malignancies, including gastrointestinal stromal tumor (GIST), seminoma, acute myelogenous leukemia (AML), and mastocytosis.
|
11896121 |
2002 |
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
CEACAM1 knockdown upregulated cell growth of HMC1.2 cells harboring KIT mutations detected in clinical mastocytosis, whereas downregulated the growth of TT cells harboring RET mutations detected in clinical MTCs.
|
28332308 |
2017 |
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Primary disorders causing constitutively hyperactivity of mast cells are called mastocytosis and are frequently due to a gain-of-function mutation of the KIT gene encoding the transmembrane tyrosine kinase receptor.
|
30350746 |
2018 |
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Activating mutations in KIT are common in gastrointestinal stromal tumors and mastocytosis.
|
14695343 |
2004 |
|
Mastocytosis
|
1.000 |
CausalMutation
|
disease |
CGI |
|
|
|
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
For those malignancies associated with KIT mutation or over-expression, imatinib offers a specific therapeutic option, yet it has no effect on D816V mutation commonly seen in sporadic mastocytosis.
|
16183119 |
2006 |
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We propose considering the KIT mutation status and bone marrow tryptase levels to aid the diagnosis of isolated CM in adult mastocytosis patients.
|
31009132 |
2019 |
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
ROSA(KIT D816V) may provide a valuable tool for studying the pathogenesis of mastocytosis and should facilitate the development of novel drugs for treating SM patients.
|
24677542 |
2014 |
|
Mastocytosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Many mast cell diseases are associated with aberrancy of c-KIT proto-oncogene resulting in tyrosine kinase activity, typically exhibiting point mutation in codon 816.
|
23211696 |
2013 |
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
However, we have previously published a report on a KIT exon 8 germline mutation, which was associated with familial GIST and mastocytosis.
|
23599150 |
2013 |
|
Mastocytosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Conversely, pathologic activation of KIT through gain-of-function mutations leads to neoplasia of KIT-dependent and KIT-positive cell types at least in three different systems: mast cells/myeloid cells--mastocytosis/acute myeloid leukemia, germ cells--seminoma, and Cajal cells--gastrointestinal stromal tumors (GISTs).
|
16082245 |
2005 |
|
Mastocytosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Molecular defects in mastocytosis: KIT and beyond KIT.
|
24745672 |
2014 |
|
Mastocytosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Thus, identifying and inhibiting the signalling pathways associated with mutated KIT gene offers a potentially important strategy for the treatment of mastocytosis.
|
23777495 |
2013 |
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
These observations suggest that although activating c-KIT mutations are associated with mast cell growth, other genes probably play a role in the cause of mastocytosis.
|
29350409 |
2018 |
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Mastocytosis is associated with an activating mutation in the KIT oncoprotein (KITD816V) that results in autophosphorylation of the KIT receptor in a ligand-independent manner.
|
16434489 |
2006 |
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The use of allele-specific quantitative polymerase chain reaction to identify KIT D816V in the peripheral blood of adults with mastocytosis has been reported to have value in the diagnosis, assessment of disease burden and management of this disease.
|
30488427 |
2018 |
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Complex karyotype and absence of mutation in the c-kit receptor in aggressive mastocytosis presenting with pelvic osteolysis, eosinophilia and brain damage.
|
11446735 |
2001 |
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
At the molecular level, recent studies have reinforced the role of activating mutations in KIT in the etiology of mastocytosis.
|
11964726 |
2001 |
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The M541L KIT substitution (KIT(M541L)) has been described to be associated with pediatric mastocytosis, to enhance growth rate of the affected cells and to confer higher sensitivity to imatinib therapy.
|
25015329 |
2014 |
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Immunostaining with antibodies against tryptase, KIT, and CD25 and molecular analysis for detection of C-KIT point mutations were performed in approximately 550/4100 myelogenous malignancies including mastocytosis, almost all subtypes of myelodysplastic syndrome (MDS), myelodysplastic/myeloproliferative syndrome (MDS/MPD), MPD, and acute myeloid leukaemia (AML).
|
15166264 |
2004 |
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We generated a Cre/loxP-based bacterial artificial chromosome transgenic mouse model that allows conditional expression of a kit gene carrying the kitD814V mutation (the murine homolog of the most common mutation in human mastocytosis, kitD816V) driven by the kit promoter.
|
21148330 |
2011 |
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Our study thus supports a role for mast cells and D816V-KIT activity in IL-6 dysregulation in mastocytosis and provides insights into the intracellular mechanisms.
|
30948489 |
2020 |
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
LHGDN |
Mutations in codon 816 of the KIT gene result in ligand-independent (constitutive) activation of KIT signaling and, thus, may play a central role in the pathogenesis of SM.
|
18314612 |
2007 |
|
Mastocytosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Here we demonstrate that crenolanib targets KIT D816 in SM and CBF AML models: crenolanib inhibits cellular proliferation and initiates apoptosis of mastocytosis cell lines expressing these mutations.
|
29137311 |
2017 |
|
Mastocytosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Acute myeloid leukemia with t(8;21)(q22;q22.1)/RUNX1-RUNX1T1 and KIT Exon 8 mutation is associated with characteristic mastocytosis and dismal outcomes.
|
31004601 |
2019 |