Oncogene
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The molecular processes governing hematopoiesis involve the interplay between lineage-specific transcription factors and a series of epigenetic tags, including DNA methylation and covalent histone tail modifications, such as acetylation, methylation, phosphorylation, SUMOylation and ubiquitylation. These post-translational modifications, which collectively constitute the 'histone code', are capable of affecting chromatin structure and gene transcription and are catalysed by opposing families of enzymes, allowing the developmental potential of hematopoietic stem cells to be dynamically regulated. The essential role of these enzymes in regulating normal blood development is highlighted by the finding that members from all families of chromatin regulators are targets for dysregulation in many hematological malignancies, and that patterns of histone modification are globally affected in cancer as well as the regulatory regions of specific oncogenes and tumor suppressors. The discovery that these epigenetic marks can be reversed by compounds targeting aberrant transcription factor/co-activator/co-repressor interactions and histone-modifying activities, provides the basis for an exciting field in which the epigenome of cancer cells may be manipulated with potential therapeutic benefits.
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Hematopoiesis is the cumulative result of intricately regulated signaling pathways that are mediated by cytokines and their receptors. Proper culmination of these diverse pathways forms the basis for an orderly generation of different cell types. ⋯ Aberration in these pathways, such as that caused by the recently identified JAK2V617F mutation, is an underlying cause for diseases such as leukemias and other myeloproliferative disorders. This recent discovery, when coupled with the fact that STATs are activated by oncoproteins such as BCR-ABL, underscores the importance of the JAK-STAT pathway in both normal cellular development and disease states.