STEROL DEPENDENT LDL-RECEPTOR GENE-TRANSCRIPTION IN LYMPHOCYTES FROM NORMAL AND CML PATIENTS

Sterol regulatory element (SRE) has been recognized to regulate variou s key genes coding for especially low density lipoprotein (LDL)-recept or, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and HMG- CoA synthase known to play a crucial role in the cholesterol feedback mechanism. The deranged cholesterol feedback mechanism has been widely recognised in initiation as well as progression of various types of c ancers including chronic myeloid leukaemia (CML). Consequently, the pr esent study was addressed to understand this phenomenon and revealed t he existence of a unique 47 kDa protein factor having affinity for thi s SRE sequence in lymphocytes from normal subjects as well as its abse nce in lymphocytes from untreated CML patients. However, this factor a ppeared when the CML patients achieved complete haematological remissi on (CHR) through alpha-interferon therapy. Further, an inverse relatio nship was also observed between sterol modulated LDL-receptor gene tra nscription and the binding affinity of this 47 kDa factor to the SRE s equence. Based upon these results we propose that alpha-interferon thr ough its receptor initiates phosphatidic acid dependent signalling whi ch in turn regulates the affinity of 47 kDa sterol regulatory element binding factor as well as LDL-receptor gene transcription in lymphocyt es from CML patients.