A new human mast cell line expressing a functional IgE receptor converts to tumorigenic growth by KIT D816V transfection.

Phosphatidylinositol 3 kinase contributes to the transformation of hematopoietic cells by the D816V c-Kit mutant.

Stem cell factor (SCF) binds the receptor tyrosine kinase c-Kit and is critical for normal hematopoiesis. Substitution of valine for aspartic acid 816 (D816V) constitutively actives human c-Kit, and this mutation is found in patients with mastocytosis, leukemia, and germ cell tumors. Immortalized murine progenitor cells (MIHCs) transduced with wild-type c-Kit proliferate in response to SCF, whe...

Ponatinib induces apoptosis in imatinib-resistant human mast cells by dephosphorylating mutant D816V KIT and silencing β-catenin signaling.

Gain-of-function mutations of membrane receptor tyrosine kinase KIT, especially gatekeeper D816V point mutation in KIT, render kinase autoactivation, disease progression, and poor prognosis. D816V KIT is found in approximately 80% of the patients with systemic mastocytosis, and is resistant to the first and second generations of tyrosine kinase inhibitors (TKI). The purpose of this investigatio...

EXEL-0862, a novel tyrosine kinase inhibitor, induces apoptosis in vitro and ex vivo in human mast cells expressing the KIT D816V mutation.

Gain-of-function mutations of the receptor tyrosine kinase KIT play a key role in the pathogenesis of systemic mastocytosis (SM), gastrointestinal stromal tumors (GISTs), and some cases of acute myeloid leukemia (AML). Whereas KIT juxtamembrane domain mutations seen in most patients with GIST are highly sensitive to imatinib, the kinase activation loop mutant D816V, frequently encountered in SM...

Synergistic growth-inhibitory effects of two tyrosine kinase inhibitors, dasatinib and PKC412, on neoplastic mast cells expressing the D816V-mutated oncogenic variant of KIT.

BACKGROUND AND OBJECTIVES In a majority of all patients with systemic mastocytosis (SM) including those with mast cell leukemia (MCL), neoplastic mast cells (MC) display the D816V-mutated variant of KIT. The respective oncoprotein, KIT D816V, exhibits constitutive tyrosine kinase (TK) activity and has been implicated in malignant cell growth. Therefore, several attempts have been made to identi...

The presence or absence of IL-3 during long-term culture of Flt3-ITD and c-Kit-D816V expressing Ba/F3 cells influences signaling outcome.