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Title: BIM is a prognostic biomarker for early prednisolone response in pediatric acute lymphoblastic leukemia
Authors: Jiang, N.
Koh, G.S.
Suang Lim, J.Y.
Yin Kham, S.K.
Ariffin, H.
Chew, F.T. 
Juh Yeoh, A.E.
Issue Date: Mar-2011
Citation: Jiang, N., Koh, G.S., Suang Lim, J.Y., Yin Kham, S.K., Ariffin, H., Chew, F.T., Juh Yeoh, A.E. (2011-03). BIM is a prognostic biomarker for early prednisolone response in pediatric acute lymphoblastic leukemia. Experimental Hematology 39 (3) : 321-329.e3. ScholarBank@NUS Repository.
Abstract: 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
Source Title: Experimental Hematology
ISSN: 0301472X
DOI: 10.1016/j.exphem.2010.11.009
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