Bone marrow stromal cells regulate caspase 3 activity in leukemic cells during chemotherapy.
The interaction between leukemic cells and stromal cells of the bone marrow microenvironment has been shown to enhance leukemic cell survival during exposure to chemotherapeutic agents. In the current study we investigated whether association of B lineage acute lymphoblastic leukemic cells with human bone marrow stromal cells altered caspase activation during chemotherapy treatment. Following treatment with Ara-C or VP-16 in vitro, caspase 3 activity in leukemic cells was consistently reduced by co-culture of leukemic cells with human bone marrow stromal cell layers. These observations suggest that the protective effect of the bone marrow microenvironment on leukemic cells may be due, in part, to regulation of caspase 3 activity.
Fortney
J E
JE
Department of Pediatrics, PO Box 9214, Health Sciences Center, West Virginia University, Morgantown, WV 26506, USA.
Zhao
W
W
Wenger
S L
SL
Gibson
L F
LF
D000208:Acute Disease; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects*; D018920:Coculture Techniques; D003561:Cytarabine / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology*; D017154:Stromal Cells / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003561:Cytarabine; D005047:Etoposide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases