SHOC2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells

SHOC2 scaffold protein has been mainly related to oncogenic ERK signaling through the RAS-SHOC2-PP1 phosphatase complex. In leukemic cells however, SHOC2 upregulation has been previously related to an increased 5-year event-free survival of pediatric pre-B acute lymphoid leukemia, suggesting that SHOC2 could be a potential prognostic marker. To address such paradoxical function, our study investigated how SHOC2 impact leukemic cells drug response. Our transcriptome analysis has shown that SHOC2 can modulate the DNA-damage mediated by p53. Notably, upon genetic inhibition of SHOC2 we observed a significant impairment of p53 expression, which in turn, leads to the blockage of key apoptotic molecules. To confirm the specificity of DNA-damage related modulation, several anti-leukemic drugs has been tested and we did confirm that the proposed mechanism impairs cell death upon daunorubicin-induced DNA damage of human lymphoid cells. In conclusion, our study uncovers new insights into SHOC2 function and reveals that this scaffold protein may be essential to activate a novel mechanism of p53-induced cell death in pre-B lymphoid cells

MLL leukemia-associated rearrangements in peripheral blood lymphocytes from healthy individuals

Chromosomal translocations are characteristic of hematopoietic neoplasias and can lead to unregulated oncogene expression or the fusion of genes to yield novel functions. In recent years, different lymphoma/leukemia-associated rearrangements have been detected in healthy individuals. In this study, we used inverse PCR to screen peripheral lymphocytes from 100 healthy individuals for the presence of MLL (Mixed Lineage Leukemia) translocations. Forty-nine percent of the probands showed MLL rearrangements. Sequence analysis showed that these rearrangements were specific for MLL translocations that corresponded to t(4;11)(q21;q23) (66%) and t(9;11) (20%). However, RT-PCR failed to detect any expression of t(4;11)(q21;q23) in our population. We suggest that 11q23 rearrangements in peripheral lymphocytes from normal individuals may result from exposure to endogenous or exogenous DNA-damaging agents. In practical terms, the high susceptibility of the MLL gene to chemically-induced damage suggests that monitoring the aberrations associated with this gene in peripheral lymphocytes may be a sensitive assay for assessing genomic instability in individuals exposed to genotoxic stress

Increased Risk for Acute Lymphoblastic Leukemia in Children with Cytochrome P-450 A(1) (CYP1A1)- and NAD(P)H:Quinone Oxidoreductase 1 (NQO1)-Inherited Gene Variants

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European cardiac nurses' current practice and knowledge on anticoagulation therapy

Background: Successful management of warfarin, new anti-thrombotic agents and self-monitoring devices requires that health care professionals effectively counsel and educate patients. Previous studies indicate that health care professionals do not always have the knowledge to provide patients with the correct information. Aims: The purpose of this study was to investigate European cardiovascular nurses' knowledge on the overall management of anticoagulation therapy and examine if this knowledge was influenced by level of education and years in clinical practice. Methods: A questionnaire including 47 items on practice patterns and knowledge on warfarin, new anticoagulants, warfarin-drug and warfarin-food interactions, and self-management of International Normalized Ratio (INR) was distributed to the attendants at a European conference in 2012. Results: The response rate was 32% (n=206), of whom 84% reported having direct patient contact. Warfarin was the most common used oral anticoagulation in daily practice. One third offered their patients both patient self-testing and patient self-management of INR. The mean total score on the knowledge questions was 28 +/- 6 (maximum possible score 53). Nurses in direct patient care had a higher mean score (p=0.011). Knowledge on warfarin and medication-interactions were low, but knowledge on warfarin-diet interactions and how to advise patients on warfarin as somewhat better. Conclusion: European cardiac nurses need to improve their knowledge and practice patterns on oral anticoagulation therapy. This area of knowledge is important in order to deliver optimal care to cardiac patients and to minimise adverse effects of the treatment