Tyrosine kinase oncogenes in normal hematopoiesis and hematological disease

E2a/Pbx1 oncogene inhibits terminal differentiation but not myeloid potential of pro-T cells

“…M-CSF is a key regulator of cells belonging to the monocyte-macrophage lineage (Stanley et al, 1994;Bourette and Rohrschneider, 2000). M-CSF-R, encoded by the c-fms protooncogene, is a member of the class III receptor tyrosine kinase (RTK) family, which includes other RTK involved in the regulation of hematopoiesis or in hematopoietic cell function: the b-receptor for plateletderived growth factor (PDGF), the receptor for SCF and Flt3/flk2 (Scheijen and Griffin, 2002). Mice with targeted disruption of the c-fms gene show increased splenic erythoid burst-forming units (BFU-E) and highproliferative potential colony-forming cells, which suggested that M-CSF-R might play a role in primitive hematopoietic cells (Dai et al, 2002).…”

Inhibition of Abl tyrosine kinase enhances nerve growth factor-mediated signaling in Bcr–Abl transformed cells via the alteration of signaling complex and the receptor turnover

“…It has been well documented that Bcr-Abl is constitutively activated in its tyrosine kinase, and plays an important role in preventing programmed cell death (Scheijen and Griffin, 2002). Imatinib mesylate, a potent inhibitor of Abl tyrosine kinase, emerged as the frontline therapy for early diseased CML patients, since it had the highest selectivity for growth inhibition of Bcr-Ablexpressing cells Druker et al, 1996Druker et al, , 2007O'Brien et al, 2003;Deininger et al, 2005).…”

Remarkable leukemogenic potency and quality of a constitutively active neurotrophin receptor, ΔTrkA

“…1,2 There is now growing evidence for involvement of multiple PTK oncogenes, their immediate downstream targets, or of proteins regulating their function in hematological malignancies. 2,3 Despite differences in structure, function and subcellular location, many of the PTK oncogenes signal through the same pathways to typically enhance proliferation and prolong viability. 3 These pathways include activation of the Ras/Raf/MAPK (mitogen-activated protein kinase), signal transducers and activators of transcription (STATs), and phosphatidylinositol 3-kinase (PI3K).…”