Leukemia research
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In a series of 105 patients with polycythemia vera, we retrospectively determined whether the JAK2(V617F) mutation correlated with severity of disease phenotype. Higher JAK2(V617F) allele burden correlated with more advanced myelofibrosis, greater splenomegaly, and higher white blood cell count, but not with age, gender, hematocrit level, or frequency of phlebotomy prior to cytoreductive therapy. Although a subgroup at increased risk for thrombosis was not clearly defined, there was a suggestion that frequency of thrombosis increased as the JAK2(V617F) allele burden increased. The JAK2(V617F) allele burden did not change significantly in treated patients with serial JAK2 analyses.
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Loss of function mutations in CCAAT/enhancer binding protein alpha (CEBPA) have been identified in acute myeloid leukemia (AML) and bi-allelic (double) CEBPA mutations are associated with improved prognosis in cases of cytogenetically normal-AML. In a subset of AML patients lacking CEBPA mutations, core promotor methylation of CEBPA has been described and is associated with a gene expression profile similar to the mutated cases including the expression of T cell associated genes such as CD7. However, the overall incidence and pattern of CEBPA mutations and core promoter methylation has not been thoroughly explored in a larger subset of AML with expression of CD7. ⋯ We find that promoter methylation accounts for half of those CD7+ cases with CEBPA dysregulating abnormalities. Furthermore, methylated cases and those with bi-allelic CEBPA mutations have similar phenotypic features including expression of CD7 and lack of co-incident NPM1 mutations. Our study suggests that methylation testing may be as important as mutation testing for identifying AML cases with CEBPA dysregulation and may be indicated in the routine prognostic workup of AML.
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Mitochondria provide ATP and Ca(2+) needed for DNA repair, but also produce reactive oxygen species (ROS), which may damage DNA. ⋯ Mitochondrial inhibition may enhance efficacy and reduce toxicity of radiation and cytotoxic drugs therapy.