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• W2146399070 abstract "Abstract Background Rearrangement of the mixed-lineage leukemia gene ( MLL ) is found in 80% of infant acute lymphoblastic leukemia (ALL) and is associated with poor prognosis and resistance to glucocorticoids (GCs). We have recently observed that GC resistance in T-ALL cell lines is associated with a proliferative metabolism and reduced expression of MLL . In this study we have further explored the relationship between MLL status and GC sensitivity. Results Negative correlation of MLL expression with GC resistance in 15 T-ALL cell lines was confirmed by quantitative RT-PCR. The absence of MLL -rearrangements suggested that this relationship represented expression of wild-type MLL . Analysis of MLL expression patterns revealed a negative relationship with cellular metabolism, proliferation and anti-apoptotic transcriptional networks. In silico analysis of published data demonstrated that reduced levels of MLL mRNA are associated with relapse and prednisolone resistance in T-ALL patients and adverse clinical outcome in children with MLL -rearranged ALL. RNAi knockdown of MLL expression in T-ALL cell lines significantly increased resistance to dexamethasone and gamma irradiation indicating an important role for wild-type MLL in the control of cellular apoptosis. Conclusions The data suggests that reduced expression of wild-type MLL can contribute to GC resistance in ALL patients both with and without MLL -translocations." @default.
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• W2146399070 date "2010-10-28" @default.
• W2146399070 modified "2023-10-15" @default.
• W2146399070 title "Influence of wild-type MLL on glucocorticoid sensitivity and response to DNA-damage in pediatric acute lymphoblastic leukemia" @default.
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• W2146399070 doi "https://doi.org/10.1186/1476-4598-9-284" @default.
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