Factor independence of human myeloid leukemia cell lines is associated with increased phosphorylation of the proto-oncogene Raf-1.

摘要: The proliferation of normal hematopoietic cells is strictly factor dependent, while leukemic cell lines and primary are frequently independent. Although autocrine growth stimulation human leukemias occasionally observed in vitro, it possible that mutations signal-transduction or cell-cycle control genes may also be important the development independence. We have previously shown proto-oncogene Raf-1, a 70-kd serine/threonine protein kinase, rapidly phosphorylated activated by factors such as granulocyte-macrophage colony-stimulating (GM-CSF), interleukin-3 (IL-3), Steel likely to an intermediate mitogenic signal transduction pathways cells. In effort better understand role abnormal independence, we compared state phosphorylation associated kinase activity Raf-1 between series factor-dependent murine-myeloid factor-independent myeloid lines. (normal neutrophils; monocytes; MO7, 32Dc13, FDC-P1), was regulated supply factor. contrast, each eight examined, HL-60, KG-1, K562, U937, JOSK-S, JOSK-M, JOSK-K, JOSK-I, expressed hyperphosphorylated with increased absence addition. To further explore relationship growth, sublines were derived from two lines, MO7 FDC-P1, culture CSF-deprived medium. Also, several transfection cDNA encoding p210BCR/ABL into three different lines: FDC-P1. case, new constitutively Raf-1. correlation hyperphosphorylation independence acute myeloblastic leukemia rate "spontaneous" (AML) vitro correlated extent phosphorylation. These results suggest evolution activation implicating which activate RAf-1 this process.