The Hepatocyte Growth Factor (HGF)/Met Axis: A Neglected Target in the Treatment of Chronic Myeloproliferative Neoplasms?

摘要: Met is the receptor of hepatocyte growth factor (HGF), a cytoprotective cytokine. Disturbing equilibrium between and its ligand may lead to inappropriate cell survival, accumulation genetic abnormalities eventually, malignancy. Abnormal activation HGF/Met axis established in solid tumours chronic haematological malignancies, including myeloma, acute myeloid leukaemia, myelogenous leukaemia (CML), myeloproliferative neoplasms (MPNs). The molecular mechanisms potentially responsible for abnormal pathways are described discussed. Importantly, inCML MPNs, production HGF independent Bcr-Abl JAK2V617F, main markers these diseases. In vitro studies showed that blocking function with neutralizing antibodies or inhibitors significantly impairs JAK2V617F-mutated cells. With personalised medicine curative treatment view, could be useful addition CML MPNs those patients high HGF/MET expression not controlled by current treatments (Bcr-Abl CML; phlebotomy, hydroxurea, JAK MPNs).