China
Africa
Explore chapters and articles related to this topic
IDH1 and IDH2 Mutations as Novel Therapeutic Targets in Acute Myeloid Leukemia (AML): Current Perspectives
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Angelo Paci, Mael Heiblig, Christophe Willekens, Sophie Broutin, Mehdi Touat, Virginie Penard-Lacronique, Stéphane de Bottona
Besides IDH-mutant cancers, abnormal accumulation of D-2HG have been observed in D-2HG aciduria (D-2HGA), a rare inherited metabolic disorder characterized by extremely variable clinical presentations ranging from fatal neonatal encephalopathy and cardiomyopathy to asymptomatic cases. Mutations in D2HGDH and IDH2 are the molecular basis of this metabolic disorder, with a tendency to a more severe clinical phenotype in IDH2-mutant patients (Kranendijk et al., 2010). Interestingly, although D-2HG levels are excessively high in patients with D-2HGA, no cancers have been reported so far in this population nor in a D-2HGA mouse model (Wang et al., 2016), which suggests that D-2HG accumulation is not sufficient alone to induce cancer. Indeed, while expression of mutant IDH enzymes were associated with increased progenitor cell marker expression and impaired cell differentiation, such epigenetics effects are not sufficient alone to drive oncogenesis (Chen et al., 2013; Chaturvedi et al., 2013; Kats et al., 2014; Shih et al., 2017; Mylonas et al., 2014). Other molecular alterations including FLT3, NRAS or overexpression of HOXA9 are required to promote full transformation of IDH-mutant clones in AML mouse models (Chen et al., 2013; Chaturvedi et al., 2013; Kats et al., 2014; Shih et al., 2017).
Endogenous neuroprotection after perinatal hypoxia-ischaemia: the resilient developing brain
Published in Journal of the Royal Society of New Zealand, 2019
Joanne O. Davidson, Simerdeep K. Dhillon, Guido Wassink, Kelly Q. Zhou, Laura Bennet, Alistair J. Gunn
Long-term follow-up of these studies is ongoing; the available evidence suggests a similar improvement in outcomes in middle childhood after mild induced hypothermia for HIE (Guillet et al. 2012; Shankaran et al. 2012; Azzopardi et al. 2014). For example, the Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY) has shown that significantly more children in the mild hypothermia group survived with an IQ score of 85 or more compared to the control group (52% vs 39%, RR 1.31, P = 0.04) (Azzopardi et al. 2014). More children in the hypothermia group survived without neurologic abnormalities than in the control group (45% vs 28%, RR 1.60, CI: 1.15, 2.22). Further, there was a significant reduction in the risk of cerebral palsy (21% vs 36%, P = 0.03) and of moderate or severe disability (22% vs 37%, P = 0.03).