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.
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.
We established an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a Chinese neonate with mastocytosis carrying heterozygous mutation (c.2447A > T (p.D816V)) in KIT gene by episomal vector (EV) reprogramming system.
We established an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a Chinese neonate with mastocytosis carrying heterozygous mutation (c.2447A > T (p.D816V)) in KIT gene by episomal vector (EV) reprogramming system.
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.
The findings also suggest that targeting the SPHK/S1P axis may provide an alternative to tyrosine kinase inhibitors, alone or in combination, for the treatment of aggressive mastocytosis and other hematological malignancies associated with the D816V-KIT mutation.
The discovery of KIT mutations as central to the pathobiology of mastocytosis has prompted development of KIT-targeted agents, including imatinib and midostaurin (approved medications for patients with advanced systemic mastocytosis), and drugs in development, like KIT D816V-specific inhibitor avapritinib.
The discovery of KIT mutations as central to the pathobiology of mastocytosis has prompted development of KIT-targeted agents, including imatinib and midostaurin (approved medications for patients with advanced systemic mastocytosis), and drugs in development, like KIT D816V-specific inhibitor avapritinib.
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.
The findings also suggest that targeting the SPHK/S1P axis may provide an alternative to tyrosine kinase inhibitors, alone or in combination, for the treatment of aggressive mastocytosis and other hematological malignancies associated with the D816V-KIT mutation.
We thereby demonstrate that caution should be taken when using the potentially very sensitive NGS technique for KIT D816V mutation analysis in mastocytosis, as many patients with SM have D816V mutation levels below the detection limit of NGS.
We thereby demonstrate that caution should be taken when using the potentially very sensitive NGS technique for KIT D816V mutation analysis in mastocytosis, as many patients with SM have D816V mutation levels below the detection limit of NGS.
Germline KIT mutations associated with mastocytosis drive a well-differentiated mast cell phenotype distinct to that of somatic KIT D816V disease, the oncogenic potential of which might be influenced by SCF and selective KIT splicing.
Although the KIT D816V mutation is typically found in adult-onset mastocytosis, it is less commonly seen in childhood-onset mastocytosis, and the frequency of KIT mutations in paediatric solitary mastocytoma is poorly documented.
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.
Bone marrow biopsies from 59 patients with mastocytosis in the skin and all available skin biopsies (n=27) were subjected to a meticulous cytological, histological, immunohistochemical, and molecular analysis for the presence of WHO-defined diagnostic criteria for systemic mastocytosis: compact mast cell infiltrates (major criterion); atypical mast cell morphology, KIT D816V, abnormal expression of CD25 by mast cells, and serum tryptase levels >20 ng/ml (minor criteria).
We demonstrate for the first time that by using a sufficiently sensitive KIT D816V mutation analysis, it is possible to detect the mutation in PB in nearly all adult mastocytosis patients.
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.
Bone marrow biopsies from 59 patients with mastocytosis in the skin and all available skin biopsies (n=27) were subjected to a meticulous cytological, histological, immunohistochemical, and molecular analysis for the presence of WHO-defined diagnostic criteria for systemic mastocytosis: compact mast cell infiltrates (major criterion); atypical mast cell morphology, KIT D816V, abnormal expression of CD25 by mast cells, and serum tryptase levels >20 ng/ml (minor criteria).
We demonstrate for the first time that by using a sufficiently sensitive KIT D816V mutation analysis, it is possible to detect the mutation in PB in nearly all adult mastocytosis patients.
Although the KIT D816V mutation is typically found in adult-onset mastocytosis, it is less commonly seen in childhood-onset mastocytosis, and the frequency of KIT mutations in paediatric solitary mastocytoma is poorly documented.
Germline KIT mutations associated with mastocytosis drive a well-differentiated mast cell phenotype distinct to that of somatic KIT D816V disease, the oncogenic potential of which might be influenced by SCF and selective KIT splicing.