To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The term epigenetics refers to biochemical modifications of chromatin that without changing the primary structure of DNA, its sequence, have an effect on chromatin function. Initially study of epigenetic changes focused on their effects on gene expression regulation, although more recently it has become apparent that epigenetics modifications have multiple roles in chromatin control including DNA repair. At present and from a clinical perspective, the term epigenetic includes three global processes: DNA methylation, histone code alterations, and more recently microRNA expression and regulation. This last process is closely inter-related with the control of DNA methylation and potentially histone code modifications. Also and more recently, a number of genetic lesions in genes such as TET2, ASXL1, IDH1 and IDH2, EZH2, and DNMT3A have been described in human leukemias. These genetic lesions have important effects on epigenetics and link both fields. From a therapeutic perspective, clinicians currently have access to a number of anti-cancer agents with either DNA-hypomethylating activity or with the capacity to induce histone deacetylase (HDAC) inhibition.
Since the late 1990s, there have been intense efforts to identify epigenetic changes in cancer, and in leukemia in particular. This work was stimulated by the realization that epigenetic alterations are very common in leukemia and that epigenetic information could have a significant translational impact by helping in the development of new prognostic biomarkers and therapeutic targets. This chapter reviews the translational information currently known pertaining epigenetics, mainly aberrant DNA methylation, and human leukemia. It includes a summary of known epigenetic defects in specific leukemias and prognostic use and clinical experience with anti-leukemia agents with known epigenetic effects.
Stefan H. Faderl, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA,
Guillermo Garcia-Manero, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA,
Hagop M. Kantarjian, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell disorders which are distinguished by cytopenias in the face of hypercellular marrows and dysplastic hematopoietic cell lines. Up into the 1970s MDS have been called “preleukemia” expressing the proximity of MDS to acute myeloid leukemia (AML), and their capacity to evolve into AML over time. Although MDS is the currently accepted term, the pathophysiology of MDS varies widely extending from abnormalities of apoptosis and differentiation to proliferation and maturation arrest. It is nowadays also better understood that there are notable differences between MDS and AML, a separation which is also underlined by the clinical manifestations and prognosis of MDS, which are primarily determined by cytopenias and not leukemic transformation. The complexity of pathophysiology and resultant heterogeneity of prognosis have led to several recent attempts to fine tune criteria for diagnosis and classification. In addition, recent years have also seen important advances of treatment with respect to hematopoietic growth factors, iron chelation, and particularly epigenetic therapy and immunomodulatory inhibitory derivatives (e.g., lenalidomide). These developments have made the care of patients with MDS more demanding but at the same time more satisfying as the possibilities for patients with MDS are now larger than before.
Email your librarian or administrator to recommend adding this to your organisation's collection.