| BIM is a prognostic biomarker for early prednisolone response in pediatric acute lymphoblastic leukemia. | |
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MedLine Citation:
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PMID: 21130142 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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OBJECTIVE: Glucocorticoids such as prednisolone (PRED) are widely used in the treatment of pediatric acute lymphoblastic leukemia. In PRED-induced apoptosis, Bcl-2 family members play important regulatory roles. However, the exact members involved remain unknown. In this study, the roles of Bcl-2 family members in PRED-induced apoptosis and their prognostic value to day 8 PRED response are evaluated. MATERIALS AND METHODS: Four clinically important acute lymphoblastic leukemia cell lines, three PRED-sensitive (697, Sup-B15, and RS4;11) and one PRED-resistant (REH) were studied. Thirty paired patient bone marrow samples were obtained at diagnosis (day 0) and after 7 days (day 8) of PRED monotherapy. Twenty-five patients had PRED good response and five PRED poor response. Differential expressions of Bcl-2 members were observed in those samples and BIM was further investigated using gene silencing technology in representative cell line Sup-B15. RESULTS: The proapoptotic BH3-only Bcl-2 family member BIM was upregulated only in PRED-sensitive cells. Receiver operating characteristic curve analysis showed that BIM expression was highly predictive of PRED response (area under the curve = 0.81; p = 0.032) in paired patient bone marrow samples and is, most excitingly, independent of molecular subtype. Patients whose BIM protein expression levels fail to upregulate at day 8 compared to day 0 (D8/D0 ratio <0.93) have significantly poorer event-free survival (60%) than those patients whose BIM protein expression levels did upregulate (92%). By silencing BIM in PRED-sensitive cells, PRED-induced apoptosis was inhibited. CONCLUSIONS: Upregulation of BIM by PRED in acute lymphoblastic leukemia cells regardless of molecular subtype is significantly prognostic of outcomes, confirming BIM's essential regulatory role in the PRED-induced apoptosis. |
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Authors:
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Nan Jiang; Grace Shimin Koh; Joshua Yew Suang Lim; Shirley Kow Yin Kham; Hany Ariffin; Fook Tim Chew; Allen Eng Juh Yeoh |
Publication Detail:
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Type: Journal Article Date: 2010-12-02 |
Journal Detail:
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Title: Experimental hematology Volume: 39 ISSN: 1873-2399 ISO Abbreviation: Exp. Hematol. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0402313 Medline TA: Exp Hematol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 321-329.e3 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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