These results suggest that both methods provide clinically useful and complementary information through the identification and/or quantification of the KIT D816V mutation in peripheral blood of patients suspected of systemic mastocytosis.
Asp-816-->Val with a subset of sporadic persistent (systemic) mastocytosis (mostly adults), and Gly-839-->Lys with (a subset of) typical pediatric (mostly cutaneous) mastocytosis.
DCC-2618 is a spectrum-selective pan KIT and PDGFRA inhibitor which blocks KIT D816V and multiple other kinase targets relevant to systemic mastocytosis.
The identification of KIT D816V mutation and the emergence of novel targeted therapies have significantly improved the diagnosis and treatment of systemic mastocytosis.
A case of systemic mastocytosis carrying the characteristic mutation at codon 816 (D816V) in the KIT gene of mast cells, with two concurrent accompanying clonal haematopoietic non-mast cell-lineage disorders, chronic myeloproliferative disease, unclassifiable and precursor B lymphoblastic leukaemia is documented.
We conclude that decreased phosphorylation and increased levels of Bim overcome the prosurvival effect of the D816V mutation and that the results warrant further investigations of the clinical effects of proteasomal inhibition in systemic mastocytosis.
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.
Because the D816V mutation was detected in the initial bone marrow specimen, strict application of three minor diagnostic criteria (spindling, CD25, D816V) enabled a diagnosis of SM-AML to be confirmed retrospectively in the initial bone marrow tissue.
In a phase I trial of avapritinib (formerly BLU-285), which targets D816V mutant KIT, for the treatment of advanced systemic mastocytosis, patients experienced rapid and durable disease control.
Here we investigated IL1β, IL6, IL13, CCL23 and clusterin plasma levels in 75 SM patients--66 indolent SM (ISM) and 9 aggressive SM--and analyzed their prognostic impact among ISM cases grouped according to the extent of hematopoietic involvement of the bone marrow cells by the KIT D816V mutation.
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.
The data from these studies indicate that, apart from KIT(D816V), other kinase targets and target pathways may play a role in disease evolution and progression, especially in patients with SM with an associated clonal hematological non-mast cell lineage disease (SM-AHNMD).
Here, the authors report significant symptomatic, cutaneous and systemic response to imatinib in a case of childhood onset indolent D816V KIT unmutated systemic mastocytosis (SM).