Transcriptional and epigenetic networks in haematological malignancy

Abstract

Identification of transcription factors as prevalent targets affected by recurring chromosomal translocations has provided the first hint for the importance of transcriptional deregulation in haematological malignancies. However, the actual molecular functions of these leukaemia-associated transcription factors on gene expression remained largely unknown until the recent discovery of their association with specific enzymatic activities that modify epigenetic codes (at DNA and/or histone levels) of downstream transcriptional targets. Intriguingly, while only just about half of acute leukaemia associates with recurring translocations, emerging evidence indicates that cryptic mutations identified in the "normal-karyotype" leukaemia also frequently affect components of epigenetic machinery. We will review these recent findings and discuss their implications in understanding the biology of the disease and in development of effective cancer therapeutics.