Influence of wild-type MLL on glucocorticoid sensitivity and response to DNA-damage in pediatric acute lymphoblastic leukemia
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 prolife...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
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BioMed Central Ltd.
2010
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| Online Access: | http://hdl.handle.net/20.500.11937/44803 |
| _version_ | 1848757105874436096 |
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| author | Beesley, A. Rampellini, J. Palmer, Misty-Lee Heng, J. Samuels, A. Firth, M. Ford, J. Kees, U. |
| author_facet | Beesley, A. Rampellini, J. Palmer, Misty-Lee Heng, J. Samuels, A. Firth, M. Ford, J. Kees, U. |
| author_sort | Beesley, A. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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 ofwild-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 thatreduced levels of MLL mRNA are associated with relapse and prednisolone resistance in T-ALL patients and adverseclinical outcome in children with MLL-rearranged ALL. RNAi knockdown of MLL expression in T-ALL cell linessignificantly increased resistance to dexamethasone and gamma irradiation indicating an important role for wildtypeMLL 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. |
| first_indexed | 2025-11-14T09:22:49Z |
| format | Journal Article |
| id | curtin-20.500.11937-44803 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:22:49Z |
| publishDate | 2010 |
| publisher | BioMed Central Ltd. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-448032017-01-30T15:16:32Z Influence of wild-type MLL on glucocorticoid sensitivity and response to DNA-damage in pediatric acute lymphoblastic leukemia Beesley, A. Rampellini, J. Palmer, Misty-Lee Heng, J. Samuels, A. Firth, M. Ford, J. Kees, U. 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 ofwild-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 thatreduced levels of MLL mRNA are associated with relapse and prednisolone resistance in T-ALL patients and adverseclinical outcome in children with MLL-rearranged ALL. RNAi knockdown of MLL expression in T-ALL cell linessignificantly increased resistance to dexamethasone and gamma irradiation indicating an important role for wildtypeMLL 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. 2010 Journal Article http://hdl.handle.net/20.500.11937/44803 BioMed Central Ltd. fulltext |
| spellingShingle | Beesley, A. Rampellini, J. Palmer, Misty-Lee Heng, J. Samuels, A. Firth, M. Ford, J. Kees, U. Influence of wild-type MLL on glucocorticoid sensitivity and response to DNA-damage in pediatric acute lymphoblastic leukemia |
| title | Influence of wild-type MLL on glucocorticoid sensitivity and response to DNA-damage in pediatric acute lymphoblastic leukemia |
| title_full | Influence of wild-type MLL on glucocorticoid sensitivity and response to DNA-damage in pediatric acute lymphoblastic leukemia |
| title_fullStr | Influence of wild-type MLL on glucocorticoid sensitivity and response to DNA-damage in pediatric acute lymphoblastic leukemia |
| title_full_unstemmed | Influence of wild-type MLL on glucocorticoid sensitivity and response to DNA-damage in pediatric acute lymphoblastic leukemia |
| title_short | Influence of wild-type MLL on glucocorticoid sensitivity and response to DNA-damage in pediatric acute lymphoblastic leukemia |
| title_sort | influence of wild-type mll on glucocorticoid sensitivity and response to dna-damage in pediatric acute lymphoblastic leukemia |
| url | http://hdl.handle.net/20.500.11937/44803 |