The molecular basis of haematological malignancies

Most cancers develop as a result of the serial accumulation of genetic mutations in the genomes of normal cells, leading to a stepwise corruption of their growth and differentiation processes and culminating in neoplastic transformation. Over the last few years, dramatic advances in DNA sequencing technologies have allowed unprecedented progress in our understanding of cancers genomes and have inaugurated the era of cancer genomics. Haematological malignancies, whose pathogenesis and classification had been amongst the best studied, have benefited particularly from these advances. In this chapter we review the key developments in the field and their impact on our understanding of the pathogenesis, classification and treatment of haematological cancers. We go on to discuss the pathogenetic effects of important examples of oncogenic mutations from the pre- and post-genomic eras and conclude with a review of the clonal evolution of haematological cancers and its impact on patient treatment.