Nihon rinsho. Japanese journal of clinical medicine
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Immunomodulatory drugs (IMiDs) are a new class of anti-inflammatory and antineoplastic agents that have structural and functional similarities with their prototype compound, thalidomide. Although thalidomide and its derivatives, lenalidomide and pomalidomide, are widely used as an essential component in the treatment of selected hematologic neoplasms including multiple myeloma, the precise mechanisms by which these agents exert anti-tumor effects have yet to be clarified. ⋯ CRBN has also been shown to be involved in IMiDs-mediated T-cell co-stimulation and cytokine production. Further studies are necessary to elucidate the CRBN-related molecular pathways that are essential for antitumor and immunomodulatory activities of IMiDs.
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Epigenetics is a cell intrinsic mechanism to maintain genomic integrity by modifying chromatin architecture independently of changes in heritable DNA sequences namely genetic code. Chromatin is composed of nucleosome cores, in which DNA(147bp) is wrapped around a core histone octamer(two each of histones H2A, H2B, H3 and H4), arranged in a "beads-on-a-string array" with linker histones and non-histone nuclear proteins. The chromatin structure could be altered by chemical modifications of DNA and histones, including methylation and acetylation, without affecting genetic codes. ⋯ Given the biological importance of epigenetic modifications, it is easy to speculate that the abnormalities of chromatin modifying enzymes and reader proteins underlie several human diseases such as cancer, inflammation and metabolic disorders. Because epigenetic states are reversible and could be modified in response to extrinsic signals, including small molecular compounds, an increased understanding of their molecular framework would allow us to treat pathological conditions caused by epigenetic alterations. Indeed, Dnmt inhibitors and HDAC inhibitors have already applied to the treatment of hematological malignancies with considerable success.
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More than 10 years have passed since imatinib as a first developed BCR-ABL tyrosine kinase inhibitor (TKI) introduced in treatment of patients with chronic myeloid leukemia (CML). In globally, there are tremendous numbers of patients on imatinib therapy. ⋯ Ponatinib is the only clinically available TKI that has activity against the T315 mutation that is resistant to all other TKIs. Currently, a choice among these potent TKIs should take into consideration the drug side effect profiles and the patient's comorbidities.