Epigenetic mechanisms regulating normal and malignant haematopoiesis: new therapeutic targets for clinical medicine.
It is now well established that epigenetic phenomena and aberrant gene regulation play a major role in carcinogenesis. These include aberrant gene silencing by imposing inactive histone marks on promoters, aberrant methylation of DNA at CpG islands, and the active repression of promoters by oncoproteins. In addition, many malignant cells also show aberrant gene activation due to constitutively active signalling. The next frontier in cancer research will be to examine how, at the molecular level, small mutations that alter the regulatory phenotype of a cell give rise after a number of cell divisions to the vast deregulation phenomena seen in malignant cells. This review outlines recent insights into how normal cell differentiation in the haematopoietic system is subverted in leukaemia and it introduces the molecular players involved in this process. It also summarises the results of recent clinical trials trying to reverse aberrant epigenetic regulation by employing agents influencing global epigenetic regulators.
Section of Experimental Haematology, Leeds Institute of Molecular Medicine, St James's University Hospital, University of Leeds, Leeds, LS97TF, UK. c.bonifer@leeds.ac.uk
Constanze
C
Bonifer
David T
DT
Bowen
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015510:Clinical Medicine; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000628:therapy*; D006410:Hematopoiesis / Q000235:genetics*; D006801:Humans
D000970:Antineoplastic Agents