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Combination of KIT gene silencing and tocopherol succinate may offer improved therapeutic approaches for human mastocytosis
Author(s) -
Ruano Irene,
Gargini Ricardo,
Izquierdo Marta
Publication year - 2010
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2009.07918.x
Subject(s) - systemic mastocytosis , gene silencing , cancer research , tyrosine kinase , biology , imatinib mesylate , receptor tyrosine kinase , proto oncogene proteins c kit , haematopoiesis , mast cell , microbiology and biotechnology , gene , kinase , stem cell factor , imatinib , receptor , immunology , genetics , stem cell , myeloid leukemia
Summary Gain‐of‐function mutations of kit tyrosine kinase receptor are associated with mastocytosis. Two subclones of the HMC1 mast leukaemia cell line were used; both express an identical KIT allele‐specific regulatory type mutation (V560G), but differ in that one also expresses an enzymatic site type mutation (D816V) that confers on them resistance to imatinib mesylate tyrosine kinase inhibitor. In both cell lines, proliferation was suppressed and apoptosis induced by the combination of KIT gene silencing and α‐tocopherol succinate (α‐TOS), a derivate of α‐tocopherol, also known as vitamin E. Furthermore, HMC1 cells with decreased kit levels by KIT silencing, failed to form tumours when xenotransplanted into immunocompromised mice and the animals were treated systemically with α‐TOS. Targeting kit in the presence of α‐TOS represents a new approach against proliferation of human mast leukaemia cell lines.