1Stem Cell Gene Therapy Research Group, INMAS Delhi.
2INMAS Delhi.
3Dr. B. R. Ambedkar Centre for Biomedical Research, Department of Biochemistry, V. P. Chest Institute, Delhi.
4Department of Biochemistry, V. P. Chest Institute, Delhi.
*Correspondence address: Stem Cell Gene Therapy Research Group (INMAS), Lucknow Road, Timar Pur, Delhi-110054, Phone: 011-91-23911712, Fax: 011-91-25737049, e-mail: gugdutta@rediffmail.com
†Contributed equally to this manuscript.
Hematopoietic stem cells (HSC), which are responsible for maintaining continuous pool of blood cells, are being used for bone marrow transplantation (BMT). However, the programmed cell death/apoptosis poses a serious problem for their optimum proliferation and differentiation after radio-and/or chemotherapy. The role of Bcl-2 (B Cell Lymphoma) protein, a Bcl-2 family member, is well established in suppressing apoptosis of HSC on irradiation and serum withdrawal. The anti-apoptotic activity of Bcl-2 is regulated by inter-and intra-family homo-/heterodimerization. Here we are proposing that the potential of Bcl-2 and its survival enhancing mutants, such as D34A and S70E, may be harnessed (gene therapy) to suppress the radiation and growth factor withdrawal induced apoptosis provided the neoplastic outcomes of these genes are regulated. The suggested hypothetical model is likely to be helpful in treating blood borne disorders and radiation injury through BMT.
Hematopoiesis, bone marrow transplantation, Bcl-2 family, structure-function relationship, dose-dependent overexpression
