Cytoplasmic micro heavy chain confers sensitivity to dexamethasone-induced apoptosis in early B-lineage acute lymphoblastic leukemia.
Most childhood acute lymphoblastic leukemia (ALL) arises from early B-lineage cells,and response to steroid treatment is critical to successful ALL therapy. To investigate the effect of the pre-B cell receptor (pre-BCR) complex on the response of leukemic cells to steroids, cytoplasmic micro protein (cyto mu) was transfected into cyto mu-, steroid-resistant early B cell lines. The presence of cyto mu and the assembled pre-BCR complex conferred sensitivity to dexamethasone-induced apoptosis. Both intrinsic and extrinsic apoptosis pathways are involved in this cell death. However, if the transfected cyto micro protein is unable to assemble the pre-BCR complex, the cells remain resistant to dexamethasone. These findings suggest a role for the pre-BCR complex in the response of ALL cells to treatment and provide insight into the mechanism of steroid response in the treatment of pre-B ALL.
Kim
Jenny M
JM
Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Fang
Junjie
J
Rheingold
Susan
S
Aplenc
Richard
R
Wasserman
Robert
R
Grupp
Stephan A
SA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001402:B-Lymphocytes / Q000473:pathology / Q000502:physiology; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D004789:Enzyme Activation; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000502:physiology*; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D054420:Pre-B Cell Receptors; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D011947:Receptors, Antigen, B-Cell; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
D061945:Caspase Inhibitors; D007143:Immunoglobulin Heavy Chains; D007148:Immunoglobulin mu-Chains; D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D051028:bcl-2-Associated X Protein; D003907:Dexamethasone; C505530:CASP8 protein, human; C506433:CASP9 protein, human; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases