In most patients with systemic mastocytosis (SM), including aggressive SM and mast cell leukemia (MCL), neoplastic cells express the oncogenic KIT mutation D816V.
In most patients with systemic mastocytosis (SM), including aggressive SM (ASM) and mast cell (MC) leukemia (MCL), neoplastic cells express the oncogenic KIT mutation D816V, which confers resistance to imatinib.
In summary, digital PCR-based KIT D816V mutation burden measurement in the tissue represents a novel biomarker with independent prognostic significance that can also be employed for monitoring disease progression and treatment response in systemic mastocytosis.
In this report, we demonstrate the cooperation between KIT D816V and loss of function of TET2 in mast cell transformation and demonstrate a more aggressive phenotype in a murine model of SM when both mutations are present in progenitor cells.
INNO-406 was found to inhibit proliferation in HMC-1.1 cells (IC(50): 30-40 nM), but not in HMC-1.2 cells or primary neoplastic cells in patients with KIT D816V-positive SM.
Investigation for presence of the activating KIT point mutation D816V is very helpful to establish a correct diagnosis of SM in all the difficult cases exhibiting a low degree of bone marrow infiltration or puzzling morphological findings.
KIT-D816V-independent oncogenic signaling in neoplastic cells in systemic mastocytosis: role of Lyn and Btk activation and disruption by dasatinib and bosutinib.
Morphologically occult involvement of normal-appearing BM by SM will be missed without appropriate clinical suspicion and pathologic evaluation by tryptase and CD25 IHC and KIT D816V mutation analysis.
Our data show that KIT D816V is a disease-propagating oncoprotein, but it does not activate MCs to release proinflammatory mediators, which may explain whymediator-related symptoms in SM occur preferentially in the context of a coexisting allergy.
Our results show that aberrant expression of CD25 with a FcɛRI(lo), FSC(lo), SSC(lo) and CD45(lo) immature phenotype of BMMC, in the absence of coexisting normal MC in the BM, was associated with multilineage involvement by the D816V KIT mutation, regardless of the diagnostic subtype of the disease (for example, indolent vs aggressive SM), which supports the utility of the immunophenotype of BMMC as a surrogate marker to screen for multilineage KIT mutation in ISM.
Our results show the presence of D816V KIT mutation in virtually all adults (93%) with indolent and aggressive forms of SM, except well-differentiated SM (29%), while other KIT mutations were rarely (< 3%) detected.
Patients with systemic mastocytosis (SM), whose MCs frequently arbor the activating D816V <i>KIT</i> mutation, may have indolent to aggressive diseases, and they may experience MC mediator related symptoms.
Recent studies show that most systemic mastocytosis (SM) patients, including indolent SM (ISM) with (ISMs+) and without skin lesions (ISMs-), carry the KIT D816V mutation in PB leukocytes.