Kaul D, Kaur M
Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Leuk Res. 1998 Aug;22(8):671-5. doi: 10.1016/s0145-2126(98)00012-5.
By making use of receptor-Ck positive lymphocytes (from normal human subjects) as well as receptor-Ck negative lymphocytes (from untreated chronic myeloid leukemic (CML) patients) as cellular models, we were able to show that receptor-Ck-dependent signalling is involved in the regulation of genes coding for Bcl-2 and cyclin D. Further, experiments directed to resolve the mechanism by which this receptor regulates these genes revealed that receptor-Ck, upon activation by cholesterol, initiates the cleavage of a 125 kDa cytoplasmic protein leading to the generation of a 47 kDa factor having specific affinity for genomic sterol regulatory element (SRE)/SRE-like sequence present in the promoter region of genes coding for Bcl-2 and cyclin D. Based upon these observations, we propose that the inability of leukemic cells to express receptor-Ck is responsible for the deregulated over-expression of genes coding for Bcl-2 and cyclin D and this phenomenon may be of importance in understanding leukemic haematopoiesis.
