Finally, new

hypotheses on mechanisms of disease development include the possibility that exposure to neurotoxicants triggers an upregulation and pathological modifications of alpha-synuclein. Mutations in the alpha-synuclein gene are responsible for rare familial Adriamycin solubility dmso cases of parkinsonism, and polymorphisms in the promoter region of this gene confer a higher susceptibility to idiopathic PD. Thus, toxicant-alpha-synuclein interactions could have deleterious consequences and play a role in pathogenetic processes in human parkinsonism. (C) 2010 Elsevier Inc. All rights reserved.”
“Drug doses, blood levels of drug metabolites and myelotoxicity during 6-mercaptopurine/methotrexate (MTX) maintenance therapy were registered for 59 adolescents (>= 10 years) and 176 non-adolescents (<10 years) with B-cell precursor acute lymphoblastic leukemia

(ALL) and a white blood cell count (WBC) <50 x 10(9)/l at diagnosis. Event-free survival was lower for adolescents than non-adolescents (pEFS(12y): 0.71 vs 0.83, P=0.04). For adolescents staying in remission, the mean WBC during maintenance therapy (mWBC) was related to age (r(S)=0.36, P=0.02), which became nonsignificant for those who relapsed (r(S)=0.05, P=0.9). The best-fit multivariate Cox regression model to predict risk of relapse included mWBC and thiopurine methyltransferase activity, which methylates mercaptopurine and reduces the intracellular availability of cytotoxic 6-thioguanine nucleotides Milciclib solubility dmso (coefficient: 0.11, P=0.02). The correlation of mWBC to the risk of relapse was more pronounced for adolescents (coefficient 0.65, P=0.003) than for non-adolescents (coefficient 0.42, P=0.04). Adolescents had higher mean neutrophil counts (P=0.002) than nonadolescents, but received

nonsignificantly lower mercaptopurine and MTX doses during maintenance therapy. Red blood cell MTX levels were significantly related to the dose of MTX among adolescents who stayed in remission (r(S)=0.38, P=0.02), which was not the case for those who developed a relapse (r(S)=0.15, P=0.60). Thus, compliance to maintenance therapy may influence the risk of relapse for adolescents with ALL. Leukemia (2010) 24, 715-720; doi: 10.1038/leu.2009.303; published online 4 February 2010″
“The closely related non-receptor others tyrosine kinases FEline Sarcoma (FES) and FEs Related (FER) are activated by cell surface receptors in hematopoietic cells. Despite the early description of oncogenic viral forms of fes, v-fes, and v-fps, the implication of FES and FER in human pathology is not known. We have recently shown that FES but not FER is necessary for oncogenic KIT receptor signaling. Here, we report that both FES and FER kinases are activated in primary acute myeloid leukemia (AML) blasts and in AML cell lines. FES and FER activation is dependent on FLT3 in cell lines harboring constitutively active FLT3 mutants.