Abstract
Acute lymphoblastic leukemia (ALL) is a heterogeneous cancer characterized by abnormal accumulation of immature blasts in the bone marrow. Glucocorticoids such as prednisolone (PRED) have been widely used in the treatment of pediatric ALL and the resistance to PRED is associated with unfavorable outcome in patients. We have identified BIM to be an important regulator of PRED-induced apoptosis, and its expression level may have prognostic value. By understanding the molecular basis of PRED-induced apoptosis, we hope that improved treatment strategies can be defined.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Bachmann PS, Piazza RG, Janes ME, Wong NC, Davies C, Mogavero A, Bhadri VA, Szymanska B, Geninson G, Magistroni V, Cazzaniga G, Biondi A, Miranda-Saavedra D, Göttgens B, Saffery R, Craig JM, Marshall GM, Gambacorti-Passerini C, Pimanda JE, Lock RB (2010) Epigenetic silencing of BIM in glucocorticoid poor-responsive pediatric acute lymphoblastic leukemia, and its reversal by histone deacetylase inhibition. Blood 116:3013–3022
Bonapace L, Bornhauser BC, Schmitz M, Cario G, Ziegler U, Niggli FK, Schafer BW, Schrappe M, Stanulla M, Bourquin JP (2010) Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance. J Clin Invest 120:1310–1323
Camilleri-Broet S, Vanderwerff H, Caldwell E, Hockenbery D (1998) Distinct alterations in mitochondrial mass and function characterize different models of apoptosis. Exp Cell Res 239:277–292
Chapman MS, Askew DJ, Kuscuoglu U, Miesfeld RL (1996) Transcriptional control of steroid-regulated apoptosis in murine thymoma cells. Mol Endocrinol 10:967–978
Chonghaile TN, Letai A (2008) Mimicking the BH3 domain to kill cancer cells. Oncogene 27(Suppl 1):S149–S157
Distelhorst CW (2002) Recent insights into the mechanism of glucocorticosteroid-induced apoptosis. Cell Death Differ 9:6–19
Flotho C, Coustan-Smith E, Pei D, Iwamoto S, Song G, Cheng C, Pui CH, Downing JR, Campana D (2006) Genes contributing to minimal residual disease in childhood acute lymphoblastic leukemia: prognostic significance of CASP8AP2. Blood 108:1050–1057
Flotho C, Coustan-Smith E, Pei D, Cheng C, Song G, Pui CH, Downing JR, Campana D (2007) A set of genes that regulate cell proliferation predicts treatment outcome in childhood acute lymphoblastic leukemia. Blood 110:1271–1277
Gross A, McDonnell JM, Korsmeyer SJ (1999) BCL-2 family members and the mitochondria in apoptosis. Genes Dev 13:1899–1911
Helmberg A, Auphan N, Caelles C, Karin M (1995) Glucocorticoid-induced apoptosis of human leukemic cells is caused by the repressive function of the glucocorticoid receptor. EMBO J 14:452–460
Jiang N, Kham SK, Koh GS, Suang Lim JY, Ariffin H, Chew FT, Yeoh AE (2011a) Identification of prognostic protein biomarkers in childhood acute lymphoblastic leukemia (ALL). J Proteomics 74:843–857
Jiang N, Koh GS, Lim JY, Kham SK, Ariffin H, Chew FT, Yeoh AE (2011b) BIM is a prognostic biomarker for early prednisolone response in pediatric acute lymphoblastic leukemia. Exp Hematol 39:321–329, 329 e321–323
Keith FJ, Bradbury DA, Zhu YM, Russell NH (1995) Inhibition of bcl-2 with antisense oligonucleotides induces apoptosis and increases the sensitivity of AML blasts to Ara-C. Leukemia 9:131–138
Kfir-Erenfeld S, Sionov RV, Spokoini R, Cohen O, Yefenof E (2010) Protein kinase networks regulating glucocorticoid-induced apoptosis of hematopoietic cancer cells: fundamental aspects and practical considerations. Leuk Lymphoma 51:1968–2005
Kroemer G, Reed JC (2000) Mitochondrial control of cell death. Nat Med 6:513–519
Lynch JT, Rajendran R, Xenaki G, Berrou I, Demonacos C, Krstic-Demonacos M (2010) The role of glucocorticoid receptor phosphorylation in Mcl-1 and NOXA gene expression. Mol Cancer 9:38
Mason KD, Khaw SL, Rayeroux KC, Chew E, Lee EF, Fairlie WD, Grigg AP, Seymour JF, Szer J, Huang DC, Roberts AW (2009) The BH3 mimetic compound, ABT-737, synergizes with a range of cytotoxic chemotherapy agents in chronic lymphocytic leukemia. Leukemia 23:2034–2041
Moalli PA, Rosen ST (1994) Glucocorticoid receptors and resistance to glucocorticoids in hematologic malignancies. Leuk Lymphoma 15:363–374
Obexer P, Certa U, Kofler R, Helmberg A (2001) Expression profiling of glucocorticoid-treated T-ALL cell lines: rapid repression of multiple genes involved in RNA-, protein- and nucleotide synthesis. Oncogene 20:4324–4336
Pui CH, Relling MV, Downing JR (2004) Acute lymphoblastic leukemia. N Engl J Med 350:1535–1548
Puthalakath H, Strasser A (2002) Keeping killers on a tight leash: transcriptional and post-translational control of the pro-apoptotic activity of BH3-only proteins. Cell Death Differ 9:505–512
Schmidt S, Rainer J, Ploner C, Presul E, Riml S, Kofler R (2004) Glucocorticoid-induced apoptosis and glucocorticoid resistance: molecular mechanisms and clinical relevance. Cell Death Differ 11(Suppl 1):S45–S55
Schmidt S, Rainer J, Riml S, Ploner C, Jesacher S, Achmuller C, Presul E, Skvortsov S, Crazzolara R, Fiegl M, Raivio T, Jänne OA, Geley S, Meister B, Kofler R (2006) Identification of glucocorticoid-response genes in children with acute lymphoblastic leukemia. Blood 107:2061–2069
Schrappe M, Reiter A, Ludwig WD, Harbott J, Zimmermann M, Hiddemann W, Niemeyer C, Henze G, Feldges A, Zintl F, Kornhuber B, Ritter J, Welte K, Gadner H, Riehm H (2000) Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. German-Austrian-Swiss ALL-BFM Study Group. Blood 95:3310–3322
Sionov RV, Spokoini R, Kfir-Erenfeld S, Cohen O, Yefenof E (2008) Mechanisms regulating the susceptibility of hematopoietic malignancies to glucocorticoid-induced apoptosis. Adv Cancer Res 101:127–248
Veis DJ, Sorenson CM, Shutter JR, Korsmeyer SJ (1993) Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell 75:229–240
Wang Z, Malone MH, He H, McColl KS, Distelhorst CW (2003) Microarray analysis uncovers the induction of the proapoptotic BH3-only protein Bim in multiple models of glucocorticoid-induced apoptosis. J Biol Chem 278:23861–23867
Wei G, Twomey D, Lamb J, Schlis K, Agarwal J, Stam RW, Opferman JT, Sallan SE, den Boer ML, Pieters R, Golub TR, Armstrong SA (2006) Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL1 and glucocorticoid resistance. Cancer Cell 10:331–342
Yeoh EJ, Ross ME, Shurtleff SA, Williams WK, Patel D, Mahfouz R, Behm FG, Raimondi SC, Relling MV, Patel A, Cheng C, Campana D, Wilkins D, Zhou X, Li J, Liu H, Pui CH, Evans WE, Naeve C, Wong L, Downing JR (2002) Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 1:133–143
Youle RJ, Strasser A (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9:47–59
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Jiang, N., Koh, G.S., Yeoh, A.E.J. (2013). Pediatric Acute Lymphoblastic Leukemia: Role of BIM Protein in Prednisolone-Induced Apoptosis. In: Hayat, M. (eds) Pediatric Cancer, Volume 4. Pediatric Cancer, vol 4. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6591-7_12
Download citation
DOI: https://doi.org/10.1007/978-94-007-6591-7_12
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-6590-0
Online ISBN: 978-94-007-6591-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)