Expression of the c‐kit gene product in normal and neoplastic mast cells but not in neoplastic basophil/mast cell precursors from chronic myelogenous leukaemia

Abstract

The expression of the c-kit gene product has been examined in normal mast cells, mast cell neoplasms, and basophil/mast cell precursors obtained from patients with chronic myelogenous leukaemia (CML). Formalin-fixed, paraffin-embedded sections or smears fixed with formalin vapour were studied by immunohistochemical methods, using a polyclonal antibody against the c-kit gene product. Normal and neoplastic mast cells showed a positive immunoreaction for c-kit gene product, but neoplastic basophil/mast cell precursors from CML patients lacked c-kit gene product by immunohistochemical and flow cytometric methods, even in cells having mast cell granules, together with or without basophil granules. Mast cell tryptase was, however, expressed in normal and neoplastic mast cells and basophil/mast cell precursors containing mast cell granules. In addition, cells of monocyte/macrophage lineage lacked c-kit gene product. These findings indicate that the c-kit gene product may play an important role in the development and function of mast cell but not of cell of basophil and monocyte/macrophage lineage.

New insights into the mechanisms of hematopoietic cell transformation by activated receptor tyrosine kinases

“…12 c-KIT expression is down-regulated during cell differentiation with the exception of mast cells that retain a high level of expression. 13 c-KIT is also expressed in melanocytes, testis, brain, vascular endothelial cells, interstitial cells of Cajal, breast glandular epithelial cells, and sweat glands. Remarkably, mutated forms of c-KIT were identified in tumors arising from most of these cell types.…”

Detection of tryptase in cytoplasmic granules of basophils in patients with chronic myeloid leukemia and other myeloid neoplasms

“…[17][18][19] Notably, in patients with CML, immature "basophillike" cells were found to react with antitryptase monoclonal antibody. 19 However, it could not be clarified whether the labeled cells were indeed basophils or MC-lineage cells. Our immunoelectron microscopy experiments clearly show that tryptase is expressed in the granule compartment of basophils in patients with CML, MDS, and IMF.…”

“…17,18 Moreover, it was found that in patients with chronic myeloid leukemia (CML), immature granulated cells with characteristics of basophils react with antibodies against tryptase. 19 However, it could not be clarified whether these cells are indeed basophils, belong to the MC lineage, or would represent an "intermediate cell. "…”

Imatinib Inhibits Proliferation of Ewing Tumor Cells Mediated by the Stem Cell Factor/KIT Receptor Pathway, and Sensitizes Cells to Vincristine and Doxorubicin-Induced Apoptosis

“…16). Neoplastic transformation has been established via mutation of c-kit gene, which results in ligand-independent activation of the receptor in a number of human tumors such as human mast cell tumors (17,18), chronic myelogenous leukemia (19), germ cell tumors (20), and gastrointestinal stromal tumors (GISTs; Refs. [21][22][23].…”