Sentences with phrase «activated by mutations»

When aberrantly activated by mutation, these signals can cause cancer and are the targets for a new class of personalized cancer drug.

For example, each patient with colon cancer could have a diagnostic analysis to determine which kinases are activated by mutation — an easy task once you know which ones to look for.

Not exact matches

Microglia are activated during Alzheimer's disease progression and may mediate an initially protective inflammatory response, a notion that is also supported by epidemiological studies linking mutations in the TREM2 gene to increased risk of Alzheimer's and other neurodegenerative diseases.

Ethionamide in particular is activated by the enzyme EthA, but some resistant forms of tuberculosis have developed mutations in the ethA gene, sparing them from the toxic effects of the transformed ethionamide.

By activating the mutations in different parts of the brain and at different stages of development, the researchers found that the two mutations affected brain circuits in different ways.

The research just published proposes that the normal biology of mRNA regulation in neurons, in which RNA is generally silenced and only activated in the correct place and time, makes it susceptible to both age - related decline and disturbance by genetic mutation.

Further, ERK1 / 2 is known to get activated by autocrine factors without mutations in Ras [31].

Thus, two subclones of the tumor in AML35 both acquired activating mutations of IDH2 at the same residue but by different mutations.

The chromosome 7 - linked form of congenital long QT syndrome (LQT2) is caused by mutations in the human ether - a-go-go-related gene (HERG) that encodes the rapidly activating delayed rectifier

This is in accordance with previous reports that decitabine and 5 - azacytidine produce a marked synergistic effect in combination with suberoylanilide hydroxamic acid and romidepsin in T - lymphoma cell lines by modulating cell cycle arrest and apoptosis.26, 27 As a mechanism of action, KMT2D mutations of B - lymphoma cells promote malignant outgrowth by perturbing methylation of H3K4 that affect the JAK - STAT, Toll - like receptor, or B - cell receptor pathway.28, 29 Here our study indicated that dual treatment with chidamide and decitabine enhanced the interaction of KMT2D with the transcription factor PU.1, thereby inactivating the H3K4me - associated signaling pathway MAPK, which is constitutively activated in T - cell lymphoma.13, 30,31 The transcription factor PU.1 is involved in the development of all hematopoietic lineages32 and regulates lymphoid cell growth and transformation.33 Aberrant PU.1 expression promotes acute myeloid leukemia and is related to the pathogenesis of multiple myeloma via the MAPK pathway.34, 35 On the other hand, PU.1 is also shown to interact with chromatin remodeler and DNA methyltransferease to control hematopoiesis and suppress leukemia.36 Our data thus suggested that the combined action of chidamide and decitabine may interfere with the differentiation and / or viability of PTCL - NOS through a PU.1 - dependent gene expression program.

The clinical relevance of our in vitro model is highlighted by the fact that 5 of the 25 activating mutations (S646F, Y652H, V658F, R724H, L783F) have been previously reported in human patients.

These mutant kinases are attractive therapeutic targets, as demonstrated by the efficacy of imatinib in BCR - ABL — positive chronic myelogenous leukemia (CML), 5 as well as in MPD associated with activating alleles involving PDGFRA or PDGFRB.2, 6,7 In addition, activating mutations in the FLT3 receptor tyrosine kinase are the most common genetic event in acute myeloid leukemia (AML), and specific inhibitors of the FMS - like tyrosine kinase 3 (FLT3) have entered late - stage clinical trials.8 Although mutations in tyrosine kinases and in other genes have been identified in a subset of MPD and AML, in many cases the genetic events that contribute to the molecular pathogenesis of these diseases remain unknown.

In 2005, the identification of an activating mutation in JAK2 (the V617F mutation) as a STAT5 - activating and disease - causing genetic alteration in a significant proportion of patients with myeloproliferative neoplasms (MPNs) has emphasized the oncogenic role of the JAK tyrosine kinases in hematologic malignancies.2 — 5 JAK2 is a member of the Janus tyrosine kinase family comprising three other mammalian non-receptor tyrosine kinases (JAK1, JAK3 and TYK2) that associate with cytokine receptors lacking intrinsic kinase activity to mediate cytokine - induced signal transduction and activation of STAT transcription factors.6 All JAKs share a similar protein structure and contain a tyrosine kinase domain at the C - terminus flanked by a catalytically inactive pseudokinase domain with kinase - regulatory activity, by an atypical SH2 domain and by a FERM domain that mediates association to the membrane - proximal region of the cytokine receptors.7, 8 Soon after the discovery of JAK2 V617F, we and others described that activating JAK1 mutations are relatively common in adult patients with T - cell acute lymphoblastic leukemia (ALL) and participate in ALL development allowing for constitutive activation of STAT5.9 — 11 Several STAT5 - activating JAK1 mutations were also reported in AML and breast cancer patients.10

«We figured that if there were going to be mutations that constitutively activated these enzymes, and that would thus be targetable by drugs, the kinase domains would be the ones to go for,» said Vogelstein.

E2 can be activated by epoxide - forming oxidants resulting in the ability to bind to DNA and form DNA adducts, which can cause mutation leading to carcinogenesis.

By activating this trigger, particular abilities can pick up new forms through mutation.