Megakaryocyte growth and development factor (MGDF)-induced acute leukemia cell proliferation and clonal growth is associated with functional c-mpl

Abstract

The effects of human recombinant megakaryocyte growth and ation of the receptor itself and of a number of transducing development factor (MGDF) (also known as thrombopoietin molecules. 27 The activation of several tyrosine kinases as well lodysplasia. [42][43][44][45][46][47][48] induces tyrosine protein phosphorylation.

Expression of thrombopoietin and its receptor (c-mpl) in chronic myelogenous leukemia

“…All French-American-British (FAB) subtypes were affected, but stimulation was greatest in M7. 14,30 Overexpression of c-mpl correlated with a poor prognosis in patients with AML. Wetzler et al 24 reported that such overexpression identified a group of patients with poor response to intensive chemotherapy.…”

Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines

“…Targeted disruption of the Flt3 gene in mice produced de®ciencies in primitive lymphoid and hematopoietic progenitors, suggesting an essential role for the gene (Mackarehtschian et al, 1995). Flt3 ligand caused a proliferative response in a considerably high percentage of AML cases (Piacibello et al, 1995;Mckenna et al, 1996;Lisovsky et al, 1996;Drexler, 1996). This suggests that the RTK is potentially important not only for normal hematopoiesis but also for leukemia cell proliferation.…”

Circulating thrombopoietin as an in vivo growth factor for blast cells in acute myeloid leukemia

“…1 Thus, serum TPO level correlates inversely with platelet count in patients with hypoplastic thrombocytopenia, including chemotherapy-induced thrombocytopenia, 2-4 aplastic anemia, [5][6][7] myelodysplastic syndromes (MDS), and congenital amegakaryocytosis, 8 whereas no correlation is observed in patients with hyperdestructive thrombocytopenia 5 ; c-mpl has been observed on the surfaces of myeloid and lymphoid human blast cancer cells. [9][10][11][12][13][14] TPO in vitro induces cell cycle activation in human acute myeloblastic leukemia (AML) blast cells, 9,10,12,13 protects these cells from programmed cell death, 13 and, in TPO nonresponding cells, is synergistic with other growth factors to support the growth of leukemic myeloid blast cells. 9,12 Until now, no study has evaluated the relationship between serum TPO levels and the presence of c-mpl functional receptor on leukemic blast cells.…”