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(2011) Autophagy

Toxic proteins infiltrating the midbrain substantia nigra can trigger the demise of dopaminergic neurons, leading to motor symptoms such as bradykinesia, resting tremor, and muscle rigidity

C.ShouvalH

Mutations of the tumor suppressor gene TP53 represent a common mutation in myeloid malignancies, occurring in 10-20% of patients with de novo myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) with profound negative impact on outcomes and a median overall survival (OS) of 6-12 months.31 Critically, the clonal burden of TP53 , that is the variant allele frequency (VAF) and/or allelic state of TP53 , is intimately tied with the clinical trajectory of these patients and is a robust, independent predictor of survival.74 Given the poor OS and lack of therapeutic options for TP53 mutant MDS/AML patients, a number of novel agents are being investigated in this patient group.8 Of these, APR-246 has evoked considerable excitement based on its robust clinical efficacy in combination with azacitidine in TP53 mutant MDS/AML patients.109 In this issue of Haematologica ,11 Maslah et al

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