Lymphocytes from CML patients lack a 47 kDa factor having affinity for a genomic sterol regulatory sequence.
Deranged cellular cholesterol homeostasis has been widely recognized in the initiation as well as progression of various types of cancers including chronic myeloid leukaemia (CML). Since the human genomic sterol regulatory element (SRE) has been shown to regulate various key genes involved in this phenomenon, the present study revealed the existence of a unique 47 kDa protein factor having affinity for this SRE sequence in lymphocytes from normal subjects, as well as its absence in lymphocytes from untreated CML patients. However, this factor appeared when these CML patients achieved complete haematological remission (CHR) through alpha-interferon therapy. Furthermore, an inverse relationship was also observed between the LDL receptor gene expression at the transcriptional level and the binding affinity of this 47 kDa protein factor to the SRE sequence. Based upon these results we propose that this factor may have a role in pathophysiology of chronic myeloid leukaemia.
Goel
R
R
Department of Experimental Medicine & Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Kaul
D
D
Varma
S
S
D000970:Antineoplastic Agents / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D050862:Oxidoreductases Acting on Sulfur Group Donors; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011973:Receptors, LDL; C497390:SREBF2 protein, human; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; D010088:Oxidoreductases; D050862:Oxidoreductases Acting on Sulfur Group Donors; C112161:thiol oxidase, 47 kDa