Abstract:Acute lymphoblastic leukemia (ALL) is the most common malignant hematological disease in childhood. Glucocorticoids are frequently used in the chemoradiotherapy regimen for ALL and can induce the apoptosis of ALL cells through several signaling pathways, but about 10% of ALL children have poor response to glucocorticoids. Studies have revealed that glucocorticoids induce the apoptosis of ALL cells by upregulating the expression of BIM gene, and BIM gene is associated with glucocorticoid resistance in childhood ALL. This article reviews the recent studies on glucocorticoid resistance in childhood ALL, especially the role of BIM and its expression products in this process.
XU Jin-Yun,LUO Jian-Ming. Association between BIM gene and glucocorticoid resistance in children with acute lymphoblastic leukemia[J]. CJCP, 2017, 19(8): 945-948.
Li Y, Buijs-Gladdines JG, Canté-Barrett K, et al. IL-7 receptor mutations and steroid resistance in pediatric T cell acute lymphoblastic leukemia: a genome sequencing study[J]. PLoS Med, 2016, 13 (12): e1002200.
[2]
Harada M, Pokrovskaja-Tamm K, Söderhäll S, et al. Involvement of miR17 pathway in glucocorticoid-induced cell death in pediatric acute lymphoblastic leukemia[J]. Leuk Lymphoma, 2012, 53 (10): 2041-2050.
[3]
Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia[J]. N Engl J Med, 2006, 354 (2): 166-178.
[4]
Yeoh AE, Tan D, Li CK, et al. Management of adult and paediatric acute lymphoblastic leukaemia in Asia: resource-stratified guidelines from the Asian Oncology Summit 2013[J]. Lancet Oncol, 2013, 14 (12): e508-e523.
[5]
Gagné V, Rousseau J, Labuda M, et al. Bim polymorphisms: influence on function and response to treatment in children with acute lymphoblastic leukemia[J]. Clin Cancer Res, 2013, 19 (18): 5240-5249.
[6]
Rambal AA, Panaguiton ZL, Kramer L, et al. MEK inhibitors potentiate dexamethasone lethality in acute lymphoblastic leukemia cells through the pro-apoptotic molecule BIM[J]. Leukemia, 2009, 23 (10): 1744-1754.
[7]
Reynolds C, Roderick JE, LaBelle JL, et al. Repression of BIM mediates survival signaling by MYC and AKT in high-risk T-cell acute lymphoblastic leukemia[J]. Leukemia, 2014, 28 (9): 1819-1827.
Hilden JM, Dinndorf PA, Meerbaum SO, et al. Analysis of prognostic factors of acute lymphoblastic leukemia in infants: report on CCG 1953 from the Children's Oncology Group[J]. Blood, 2006, 108 (2): 441-451.
[10]
Jiang N, Koh GS, Lim JY, et al. BIM is a prognostic biomarker for early prednisolone response in pediatric acute lymphoblastic leukemia[J]. Exp Hematol, 2011, 39 (3): 321-329.e3.
[11]
Schultz KR, Pullen DJ, Sather HN, et al. Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG) [J]. Blood, 2007, 109 (3): 926-935.
[12]
Horton T. Yin and yang of glucocorticoid receptors in apoptosis[J]. Blood, 2015, 125 (2): 209-211.
[13]
Hata AN, Engelman JA, Faber AC. The BCL2 family: key mediators of the apoptotic response to targeted anticancer therapeutics[J]. Cancer Discov, 2015, 5 (5): 475-487.
[14]
Sionov RV, Vlahopoulos SA, Granot Z. Regulation of Bim in health and disease[J]. Oncotarget, 2015, 6 (27): 23058-23134.
[15]
Kovarova M, Koller BH. PGE2 promotes apoptosis induced by cytokine deprivation through EP3 receptor and induces Bim in mouse mast cells[J]. PLoS One, 2014, 9 (7): e102948.
[16]
Rohrbeck L, Gong JN, Lee EF, et al. Hepatocyte growth factor renders BRAF mutant human melanoma cell lines resistant to PLX4032 by downregulating the pro-apoptotic BH3-only proteins PUMA and BIM[J]. Cell Death Differ, 2016, 23 (12): 2054-2062.
[17]
Caro-Maldonado A, Tait SW, Ramirez-Peinado S, et al. Glucose deprivation induces an atypical form of apoptosis mediated by caspase-8 in Bax-, Bak-deficient cells[J]. Cell Death Differ, 2010, 17 (8): 1335-1344.
[18]
Coloff JL, Macintyre AN, Nichols AG, et al. Akt-dependent glucose metabolism promotes Mcl-1 synthesis to maintain cell survival and resistance to Bcl-2 inhibition[J]. Cancer Res, 2011, 71 (15): 5204-5213.
[19]
Liu T, Kishton RJ, Macintyre AN, et al. Glucose transporter 1-mediated glucose uptake is limiting for B-cell acute lymphoblastic leukemia anabolic metabolism and resistance to apoptosis[J]. Cell Death Dis, 2014, 5: e1470.
[20]
Ng KP, Hillmer AM, Chuah CT, et al. A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer[J]. Nat Med, 2012, 18 (4): 521-528.
[21]
Erlacher M, Michalak EM, Kelly PN, et al. BH3-only proteins Puma and Bim are rate-limiting for gamma-radiation- and glucocorticoid-induced apoptosis of lymphoid cells in vivo[J]. Blood, 2005, 106 (13): 4131-4138.
[22]
Bachmann PS, Gorman R, Papa RA, et al. Divergent mechanisms of glucocorticoid resistance in experimental models of pediatric acute lymphoblastic leukemia[J]. Cancer Res, 2007, 67 (9): 4482-4490.
[23]
Wang Z, Malone MH, He H, et al. Microarray analysis uncovers the induction of the proapoptotic BH3-only protein Bim in multiple models of glucocorticoid-induced apoptosis[J]. J Biol Chem, 2003, 278 (26): 23861-23867.
[24]
Akahane K, Sanda T, Mansour MR, et al. HSP90 inhibition leads to degradation of the TYK2 kinase and apoptotic cell death in T-cell acute lymphoblastic leukemia[J]. Leukemia, 2016, 30 (1): 219-228.
[25]
Ploner C, Rainer J, Niederegger H, et al. The BCL2 rheostat in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia[J]. Leukemia, 2008, 22 (2): 370-377.
[26]
Saenz GJ, Hovanessian R, Gisis AD, et al. Glucocorticoid-mediated co-regulation of RCAN1-1, E4BP4 and BIM in human leukemia cells susceptible to apoptosis[J]. Biochem Biophys Res Commun, 2015, 463 (4): 1291-1296.
[27]
Hall CP, Reynolds CP, Kang MH. Modulation of glucocorticoid resistance in pediatric T-cell acute lymphoblastic leukemia by increasing BIM expression with the PI3K/mTOR inhibitor BEZ235[J]. Clin Cancer Res, 2016, 22 (3): 621-632.
[28]
Prenek L, Boldizsár F, Kugyelka R, et al. The regulation of the mitochondrial apoptotic pathway by glucocorticoid receptor in collaboration with Bcl-2 family proteins in developing T cells[J]. Apoptosis, 2017, 22 (2): 239-253.
[29]
Czabotar PE, Lessene G, Strasser A, et al. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy[J]. Nat Rev Mol Cell Biol, 2014, 15 (1): 49-63.
[30]
Bachmann PS, Gorman R, Mackenzie KL, et al. Dexamethasone resistance in B-cell precursor childhood acute lymphoblastic leukemia occurs downstream of ligand-induced nuclear translocation of the glucocorticoid receptor[J]. Blood, 2005, 105 (6): 2519-2526.
[31]
Zhao YN, Guo X, Ma ZG, et al. Pro-apoptotic protein BIM in apoptosis of glucocorticoid-sensitive and -resistant acute lymphoblastic leukemia CEM cells[J]. Med Oncol, 2011, 28 (4): 1609-1617.
[32]
Kfir-Erenfeld S, Haggiag N, Biton M, et al. miR-103 inhibits proliferation and sensitizes hemopoietic tumor cells for glucocorticoid-induced apoptosis[J]. Oncotarget, 2017, 8 (1): 472-489.
[33]
Jing D, Bhadri VA, Beck D, et al. Opposing regulation of BIM and BCL2 controls glucocorticoid-induced apoptosis of pediatric acute lymphoblastic leukemia cells[J]. Blood, 2015, 125 (2): 273-283.
[34]
Heidari N, Miller AV, Hicks MA, et al. Glucocorticoid-mediated BIM induction and apoptosis are regulated by Runx2 and c-Jun in leukemia cells[J]. Cell Death Dis, 2012, 3: e349.
[35]
Soh SX, Lim JY, Huang JW, et al. Multi-agent chemotherapy overcomes glucocorticoid resistance conferred by a BIM deletion polymorphism in pediatric acute lymphoblastic leukemia[J]. PLoS One, 2014, 9 (8): e103435.
[36]
Korfi K, Smith M, Swan J, et al. BIM mediates synergistic killing of B-cell acute lymphoblastic leukemia cells by BCL-2 and MEK inhibitors[J]. Cell Death Dis, 2016, 7: e2177.
[37]
Gu L, Zhou C, Liu H, et al. Rapamycin sensitizes T-ALL cells to dexamethasone-induced apoptosis[J]. J Exp Clin Cancer Res, 2010, 29: 150.
[38]
Souid S, Najjaa H, Riahi-Chebbi I, et al. Allium roseum L. extract exerts potent suppressive activities on chronic myeloid leukemia K562 cell viability through the inhibition of BCR-ABL, PI3K/Akt, and ERK1/2 pathways and the abrogation of VEGF secretion[J]. Nutr Cancer, 2017, 69 (1): 117-130.
[39]
Pétigny-Lechartier C, Duboc C, Jebahi A, et al. The mTORC1/2 inhibitor AZD8055 strengthens the efficiency of the MEK inhibitor trametinib to reduce the Mcl-1/[Bim and Puma] ratio and to sensitize ovarian carcinoma cells to ABT-737[J]. Mol Cancer Ther, 2017, 16 (1): 102-115.
[40]
Liu Y, Ge J, Li Q, et al. Low-dose anisomycin sensitizes glucocorticoid-resistant T-acute lymphoblastic leukemia CEM-C1 cells to dexamethasone-induced apoptosis through activation of glucocorticoid receptor and p38-MAPK/JNK[J]. Leuk Lymphoma, 2014, 55 (9): 2179-2188.
[41]
Han J, Lin M, Zhou D, et al. Huang Qi Huai granules induce apoptosis in acute lymphoblastic leukemia cells through the Akt/FoxO1 pathway[J]. Cell Physiol Biochem, 2016, 38 (5): 1803-1814.
[42]
Alford SE, Kothari A, Loeff FC, et al. BH3 inhibitor sensitivity and Bcl-2 dependence in primary acute lymphoblastic leukemia cells[J]. Cancer Res, 2015, 75 (7): 1366-1375.
[43]
Del Gaizo Moore V, Schlis KD, Sallan SE, et al. BCL-2 dependence and ABT-737 sensitivity in acute lymphoblastic leukemia[J]. Blood, 2008, 111 (4): 2300-2309.
[44]
Roy MJ, Vom A, Czabotar PE, et al. Cell death and the mitochondria: therapeutic targeting of the BCL-2 family-driven pathway[J]. Br J Pharmacol, 2014, 171 (8): 1973-1987.