Currently, midostaurin is the only approved TKI as monotherapy for aggressive systemic mastocytosis (SM), SM with associated hematological neoplasm, or mast cell leukemia displaying a KIT mutation as well as in combination with standard intensive chemotherapy for adult patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML).
We used immunohistochemistry to detect in situ expression of tryptase and chymase by mast cells of a patient with urticaria pigmentosa and aggressive systemic mastocytosis, whose pathologic mast cells are clonally derived and chronically stimulated by KIT because they all contain the same point mutation causing constitutive activation of KIT.
To determine the role of c-KIT in the pathogenesis of mastocytosis, we examined tissue and cells isolated from a patient with UP and aggressive systemic mastocytosis with massive splenic involvement.
It ranges from skin lesions as cutaneous mastocytosis (CM) which may spontaneously regress to highly aggressive neoplasms with multiorgan involvement corresponding to some aggressive systemic mastocytosis (ASM), mast cell leukemia (MCL), and/or mast cell sarcoma (MCS).There is increasing evidence of CD30 expression in neoplastic MCs of the bone marrow.
Recent studies have indicated that CD30 is frequently expressed in aggressive systemic mastocytosis and mast cell leukemia but infrequently in indolent systemic mastocytosis, and may be a useful marker for distinguishing these subtypes of systemic mastocytosis from one another.
In April 2017, midostaurin was approved in the USA for the treatment of adult patients with newly diagnosed, FMS-like tyrosine kinase 3 (FLT3) mutation-positive acute myeloid leukaemia (AML) [in combination with standard cytarabine and daunorubicin induction, and cytarabine consolidation], or aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated haematological neoplasm (SM-AHN) or mast cell leukaemia (MCL) [collectively known as advanced SM].
Analysis using Kaplan-Meier survival curves showed a mean healing time of 73·1 days for ASM plus SC (ASM) treated ulcers in comparison with 83·5 days for comparison group ulcers treated with SC alone (Log rank test, χ<sup>2</sup> 5·779, P = 0·016) within 12 weeks.
Analysis using Kaplan-Meier survival curves showed a mean healing time of 73·1 days for ASM plus SC (ASM) treated ulcers in comparison with 83·5 days for comparison group ulcers treated with SC alone (Log rank test, χ<sup>2</sup> 5·779, P = 0·016) within 12 weeks.
Currently, midostaurin is the only approved TKI as monotherapy for aggressive systemic mastocytosis (SM), SM with associated hematological neoplasm, or mast cell leukemia displaying a KIT mutation as well as in combination with standard intensive chemotherapy for adult patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML).
We previously showed that integrin α7 is a novel marker of the contractile ASM phenotype suggesting that targeting this protein may offer new avenues to counter the increase in ASM cell mass that underlies airways hyperresponsiveness (AHR) in asthma.
Stretching activated strips of airway smooth muscle (ASM) significantly affects both active force and stiffness due to a temporary reduction of the proportion of cycling myosin cross bridges that are bound to their actin binding sites.
Early clinical evaluation of BLU-285 in a phase 1 study has demonstrated marked activity in patients with diseases associated with <i>KIT</i> (aggressive systemic mastocytosis and gastrointestinal stromal tumor) and <i>PDGFRA</i> (gastrointestinal stromal tumor) activation loop mutations.
Early clinical evaluation of BLU-285 in a phase 1 study has demonstrated marked activity in patients with diseases associated with <i>KIT</i> (aggressive systemic mastocytosis and gastrointestinal stromal tumor) and <i>PDGFRA</i> (gastrointestinal stromal tumor) activation loop mutations.