Hepatocyte growth factor receptor c-MET is associated with FAS and when activated enhances drug-induced apoptosis in pediatric B acute lymphoblastic leukemia with TEL-AML1 translocation.
Expression of c-MET, the HGF (hepatocyte growth factor) tyrosine kinase receptor, was investigated in pediatric B-acute lymphoblastic leukemia (ALL) patients. c-MET was found to be expressed in normal B cells and in B-ALL patients with the t(12;21) TEL-AML1 translocation, but it is not expressed in the most part of B-ALL without the t(12;21). We also found that c-MET, related to proliferation and protection from apoptosis, is associated with the pro-apoptotic protein FAS in TEL-AML1 B-ALL cells and in normal B lymphocytes. The possible role of this protein complex in drug-induced apoptosis was thus investigated in REH TEL-AML1 B-ALL cell line. REH cells prestimulated with HGF and treated with doxorubicin had shown a higher apoptotic rate than non-HGF-prestimulated ones (p = 0.03). REH cells stimulated with IL-3 and treated with doxorubicin did not undergo apoptosis more than nonstimulated cells, demonstrating that increased proliferation in itself is not directly related to the higher apoptotic sensitivity observed with HGF stimulation. These results indicate that c-MET activation enhances specifically FAS-mediated apoptosis in TEL-AML1 ALL cells and, considering that the c-MET/FAS complex is present only in normal B lymphocytes and in TEL-AML1 leukemias, this implies that it may have an important contribution in cellular homeostasis and in high sensitivity of TEL-AML1 ALL to chemotherapeutic regimens.
Accordi
Benedetta
B
Oncohematology Laboratory, Department of Pediatrics, University of Padova, 35128, Padova Italy. benedetta.accordi@unipd.it
Pillozzi
Serena
S
Dell'Orto
Marta Campo
MC
Cazzaniga
Giovanni
G
Arcangeli
Annarosa
A
Kronnie
Geertruy Te
GT
Basso
Giuseppe
G
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism; D045744:Cell Line, Tumor; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D021381:Protein Transport; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*; D000097764:ETS Translocation Variant 6 Protein
D000903:Antibiotics, Antineoplastic; D050676:Core Binding Factor Alpha 2 Subunit; D004317:Doxorubicin; D007377:Interleukin-3; D050783:Proto-Oncogene Proteins c-ets; D019859:Proto-Oncogene Proteins c-met; D012313:RNA; D012097:Repressor Proteins; D019014:fas Receptor; D000097764:ETS Translocation Variant 6 Protein; C493728:RUNX1 protein, human