Mecanismos moleculares emergentes y células madre leucémicas en la quimiorresistencia de tumores hematológicos
Portada: Tiempos de epidemia                                    Fotógrafos: Laura Aguilera, David Sarmiento y Camila Idrovo
pdf (Español (España))

Palavras-chave

Leucemia
quimiorresistencia
células madre
metabolismo tumoral
supervivenci

Como Citar

Rey-Caro, L. A., Pinzón, P., & Cruz-Rodríguez, N. (2020). Mecanismos moleculares emergentes y células madre leucémicas en la quimiorresistencia de tumores hematológicos. Salud UIS, 52(2), 129–144. https://doi.org/10.18273/revsal.v52n2-2020007

Resumo

Las leucemias agudas son trastornos clonales originados a partir de células hematopoyéticas primitivas multipotenciales que se caracterizan por la proliferación, diferenciación y maduración aberrante de células progenitoras leucémicas como resultado de varios eventos genéticos y epigenéticos. Aunque en la actualidad se han implementado diferentes esquemas de quimioterapia para mejorar el pronóstico de los pacientes, las leucemias agudas representan una malignidad hematológica con pobre desenlace clínico y bajas tasas de supervivencia en pacientes pediátricos y adultos Colombianos. Uno de los principales obstáculos para el tratamiento exitoso del cáncer es el desarrollo de resistencia a los medicamentos durante la quimioterapia y la enfermedad recurrente. En el estudio de la biología de las células tumorales, se reconoce que los diversos cambios oncogénicos y la evolución clonal que sufren las células tumorales, son cambios biológicos que les confieren mecanismos de resistencia a la quimioterapia convencional, que a su vez se traducen en un incremento en las tasas de mortalidad y/o el aumento de recaídas en los pacientes que padecen esta enfermedad. Por lo tanto, el estudio de los mecanismos empleados por las células leucémicas para escapar del efecto citotóxico del tratamiento empleado para combatir la enfermedad es un objetivo primordial de la investigación en cáncer. En este contexto, el objetivo del presente artículo es hacer una revisión detallada de los avances más recientes en la comprensión de los mecanismos involucrados en la resistencia tumoral en leucemias, haciendo especial énfasis en el papel que desempeñan las células madre leucémicas y el metabolismo tumoral en la quimiorresistencia de este grupo de enfermedades. El conocimiento de los mecanismos de resistencia tumoral, así como el entendimiento detallado de las interacciones entre las células normales y leucémicas en el microambiente de la médula ósea, son prometedores blancos terapéuticos de las leucemias agudas. 

https://doi.org/10.18273/revsal.v52n2-2020007
pdf (Español (España))

Referências

1. Estey EH, Faderl SH, Kantarjian H. Hematologic Malignancies: Acute Leukemias. In Springer; 2008. 77-288 p.
2. Juliusson G, Hough R. Leukemia. Prog Tumor Res. 2016; 43: 87-100. doi: 10.1159/000447076.
3. Instituto Nacional de Cancerología ESE. Análisis de la Situación del Cáncer en Colombia 2015. Primera edición. Bogotá DC: Instituto Nacional de Cancerología ESE; 2017.
4. Villalba C, Martínez PA, Acero H. Caracterización clínico-epidemiológica de los pacientes pediátricos con leucemias agudas en la Clínica Universitaria Colombia. Serie de casos 2011-2014. Pediatria. 2016; 49(1): 17-22. doi: 10.1016/j.rcpe.2016.01.002.
5. Katz AJ, Chia VM, Schoonen WM, Kelsh MA. Acute lymphoblastic leukemia: an assessment of international incidence, survival, and disease burden. Cancer Causes Control. 2015; 26(11): 1627-1642. doi: 10.1007/s10552-015-0657-6.
6. Pastore F, Dufour A, Benthaus T, Metzeler KH, Maharry KS, Schneider S, et al. Combined molecular and clinical prognostic index for relapse and survival in cytogenetically normal acute myeloid leukemia. J Clin Oncol. 2014; 32(15): 1586-1594. doi: 10.1200/ JCO.2013.52.3480.
7. Paul S, Kantarjian H, Jabbour EJ. Adult acute lymphoblastic leukemia. Mayo Clinic Proceedings. 2016; 91(11): 1645-1666. doi: 10.1016/j. mayocp.2016.09.010.
8. Miranda-Filho A, Piñeros M, Ferlay J, Soerjomataram I, Monnereau A, Bray F. Epidemiological patterns of leukaemia in 184 countries: a population-based study. Lancet Haematol. 2018; 5(1): e14-24. doi: 10.1016/S2352-3026(17)30232-6.
9. Pardo C, De Vries E, Buitrago L, Gamboa Ó. Atlas de mortalidad por cáncer en Colombia. Cuarta Edición. 2017. 120 p. ISBN: 9789588963129.
10. Nørgaard JM, Olesen LH, Hokland P. Changing picture of cellular drug resistance in human leukemia. Crit Rev Oncol Hematol. 2004; 50(1): 39-49. doi: 10.1016/S1040-8428(03)00173-2.
11. Cervantes A. Investigación sobre cáncer en españa: de la biología molecular a la clínica. Capítulo 10: Resistencia a la quimioterapia: mecanismos y vías de modulación. In Esteve Org. 2018; 93-99.
12. Dyczynski M, Vesterlund M, Björklund AC, Zachariadis V, Janssen J, Gallart-Ayala H, et al. Metabolic reprogramming of acute lymphoblastic leukemia cells in response to glucocorticoid treatment. Cell Death Dis. 2018; 9(9): 846. doi: 10.1038/s41419-018-0625-7.
13. Hasan S, Taha R, Omri H El. Current opinions on chemoresistance: An overview. Bioinformation. 2018; 14(2): 80-85. doi: 10.6026/97320630014080.
14. Bugler J, Kinstrie R, Scott MT, Vetrie D. Epigenetic Reprogramming and Emerging Epigenetic Therapies in CML. Front Cell Dev Biol. 2019; 7: 1-14. doi: 10.3389/fcell.2019.00136.
15. Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: Role of ATP-dependent transporters. Nat Rev Cancer. 2002; 2(1): 48-58. doi: 10.1038/nrc706.
16. Nørgaard JM, Hokland P. Biology of multiple drug resistance in acute leukemia. Int J Hematol. 2000; 72(3): 290-297.
17. Tafuri A, Gregorj C, Petrucci MT, Ricciardi MR, Mancini M, Cimino G, et al. MDR1 protein expression is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia. Blood. 2002; 100(3): 974- 981. doi: 10.1182/blood-2006-05-021071.
18. Samuel S, Beljanski V, Van Grevenynghe J, Richards S, Ben Yebdri F, He Z, et al. BCL-2 inhibitors sensitize therapy-resistant chronic lymphocytic leukemia cells to VSV oncolysis. Mol Ther. 2013; 21(7): 1413-1423. doi: 10.1038/mt.2013.91.
19. Lagadinou ED, Sach A, Callahan K, Rossi RM, Neering SJ, Minhajuddin M, et al. BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells. Cell Stem Cell. 2013; 12(3): 329-341. doi: 10.1016/j. stem.2012.12.013.
20. Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, Snyder N, et al. Drug resistance in cancer: an overview. Cancers (Basel). 2014; 6(3): 1769-1692. doi: 10.3390/cancers6031769.
21. Kruh GD. Introduction to resistance to anticancer agents. Oncogene. 2003; 22(47): 7262-7264. doi: 10.1038/sj.onc.1206932.
22. Eppert K, Takenaka K, Lechman ER, Waldron L, Nilsson B, Van Galen P, et al. Stem cell gene expression programs influence clinical outcome in human leukemia. Nat Med. 2011; 17(9): 1086-1093. doi: 10.1038/nm.2415.
23. Dromparis P, Sutendra G, Michelakis ED. Metabolic modulation as a novel cancer treatment. Heart Metab. 2011; 51: 20-26.
24. Furth J, Kahn MC, Breedis C. The transmission of Leukemia of mice with a Single Cell. Am J Cancer. 1937; 31(2): 276-282. doi: 10.1158/ajc.1937.276.
25. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997; 3(7): 730-737. doi: 10.1038/nm0798-822.
26. Bruce WR, Van Der Gaag H. A quantitative assay for the number of murine lymphoma cells capable of proliferation in vivo. Nature. 1963; 199(4888): 79-80. doi: 10.1038/199079a0.
27. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994; 367(6464): 645-648. doi: 10.1038/367645a0.
28. Sell S. Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol. 2004; 51(1): 1-28. doi: 10.1016/j.critrevonc.2004.04.007.
29. Crews LA, Jamieson CHM. Selective elimination of leukemia stem cells: hitting a moving target. Cancer Lett. 2013; 338(1): 15-22. doi: 10.1016/j. canlet.2012.08.006.
30. Heidel F, Solem FK, Breitenbuecher F, Lipka DB, Kasper S, Thiede MH, et al. Clinical resistance to the kinase inhibitor PKC412 in acute myeloid leukemia by mutation of Asn-676 in the FLT3 tyrosine kinase domain. Blood. 2006; 107(1): 293- 300. doi: 10.1182/blood-2005-06-2469.
31. Lessard J, Sauvageau G. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature. 2003 ;423: 255-260. doi: 10.1038/ nature01572.
32. Mantilla C, Suárez-Mellado, Duque-Jaramillo A, Navas MC. Mecanismos de señalización por β-catenina y su papel en la carcinogénesis. CES Med. 2015; 29(1): 109-128.
33. Zhao C, Blum J, Chen A, Kwon HY, Jung SH, Cook JM, et al. Loss of β-catenin impairs the renewal of normal and CML stem cells in vivo. Cancer Cell. 2007; 12(6): 528-41. doi: 10.1016/j.ccr.2007.11.003.
34. Dierks C, Beigi R, Guo GR, Zirlik K, Stegert MR, Manley P, et al. Expansion of Bcr-abl-positive leukemic stem cells is dependent on hedgehog pathway activation. Cancer Cell. 2008; 14(3): 238-249. doi: 10.1016/j.ccr.2008.08.003.
35. Jaiswal S, Jamieson C, Pang W, Park C, Chao M, Majeti R, et al. CD47 is up-regulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell. 2009; 138(2): 271-285. doi: 10.1038/jid.2014.371.
36. Ishikawa F, Yoshida S, Saito Y, Hijikata A, Kitamura H, Tanaka S, et al. Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region. Nat Biotechnol. 2007; 25(11): 1315-1321. doi: 10.1038/nbt1350.
37. Komorowska K, Doyle A, Wahlestedt M, Subramaniam A, Debnath S, Chen J, et al. Hepatic leukemia factor maintains quiescence of hematopoietic stem cells and protects the stem cell pool during regeneration. Cell Rep. 2017; 21(12): 3514-3523. doi: 10.1016/j.celrep.2017.11.084.
38. Follini E, Marchesini M, Roti G. Strategies to overcome resistance mechanisms in t-cell acute lymphoblastic leukemia. Int J Mol Sci. 2019; 20(12): pii: E3021. doi: 10.3390/ijms20123021.
39. Mullighan CG. The molecular genetic makeup of acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2012; 2012: 389-396. doi: 10.1182/asheducation-2012.1.389.
40. Svensson E, Vidovic K, Lassen C, Richter J, Olofsson T, Fioretos T, et al. Deregulation of the Wilms’ tumour gene 1 protein (WT1) by BCR/ ABL1 mediates resistance to imatinib in human leukaemia cells. Leukemia. 2007; 21(12): 2485- 2594. doi: 10.1038/sj.leu.2404924.
41. Zhao C, Chen A, Jamieson CH, Fereshteh M, Abrahamsson A, Blum J, et al. Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia. Nature. 2009; 458(7239): 776- 779. doi: 10.1038/nature07737.
42. Lobo NA, Shimono Y, Qian D, Clarke MF. The biology of cancer stem cells. Annu Rev Cell Dev Biol. 2007; 23: 675-699. doi: 10.1146/annurev. cellbio.22.010305.104154.
43. Nair RR, Tolentino J, Hazlehurst LA. The bone marrow microenvironment as a sanctuary for minimal residual disease in CML. Biochem Pharmacol. 2010; 80(5): 602-12. doi: 10.1016/j. bcp.2010.04.003.

44. Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005; 5(4): 275-284. doi: 10.1038/nrc1590.
45. Terwijn M, Zeijlemaker W, Kelder A, Rutten AP, Snel AN, Scholten WJ, et al. Leukemic stem cell frequency: A strong biomarker for clinical outcome in acute myeloid leukemia. PLoS One. 2014; 9(9): 7-9. doi: 10.1371/journal.pone.0107587.
46. Gentles A, Plevritis S, Majeti R, Alizadeh A. A Leukemic Stem Cell Gene Expression Signature is associated with clinical outcomes in acute myeloid leukemia. JAMA. 2010; 304(24): 2706-2715. doi: 10.1038/jid.2014.371.
47. Goldman JM, Green AR, Holyoake T, Jamieson C, Mesa R, Mughal T, et al. Chronic myeloproliferative diseases with and without the Ph chromosome: Some unresolved issues. Leukemia. 2009; 23(10): 1708-1715. doi: 10.1038/leu.2009.142.
48. Corbin A, Agarwal A, Loriaux M, Cortes J, Deininger M, Druker B. Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. J Clin Invest. 2011; 121(1): 396-409. doi: 10.1172/ JCI35721DS1.
49. George AA, Franklin J, Kerkof K, Shah AJ, Price M, Tsark E, et al. Detection of leukemic cells in the CD34+CD38- bone marrow progenitor population in children with acute lymphoblastic leukemia. Blood. 2001; 97(12): 3925-3930. doi: 10.1182/ blood.V97.12.3925.
50. Valle-Mendiola A, Soto-Cruz I. Metabolismo energético y cáncer. Rev Espec Ciencias Salud. 2014; 17(2): 108-113.
51. Alonso RA, Pérez Cutiño Maité, Vidal Pérez Z, Vidal Pérez A. Papel de la reprogramación metabólica en la carcinogénesis. Corr Cient Med. 2016; 20(2): 292-304.
52. Phan LM, Yeung SCJ, Lee MH. Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies. Cancer Biol Med. 2014; 11(1): 1-19. doi: 10.7497/j. issn.2095-3941.2014.01.001.
53. Cairns RA, Harris I, Mccracken S, Mak TW. Cancer cell metabolism. Cold Spring Harb Symp Quant Biol. 2011;76: 299-311. doi: 10.1101/ sqb.2011.76.012856.
54. Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell. 2011; 144(5): 646-674. doi: 10.1016/j.cell.2011.02.013.
55. Lu J, Tan M, Cai Q. The Warburg effect in tumor progression: Mitochondrial oxidative metabolism as an anti-metastasis mechanism. Cancer Letters. 2015; 356(2 Pt A): 156-64. doi: 10.1016/j. canlet.2014.04.001.
56. Pavlova NN, Thompson CB. The emerging hallmarks of cancer metabolism. Cell Metab. 2016; 23(1): 27-47. doi: 10.1016/j.cmet.2015.12.006.
57. Spinelli JB, Haigis MC. The multifaceted contributions of mitochondria to cellular metabolism. Nat Cell Biol. 2018;20(7):745–54. doi: 10.1038/s41556-018-0124-1.
58. Shaw RJ. Glucose metabolism and cancer. Curr Opin Cell Biol. 2006;18(6):598–608. doi: 10.1016/j. ceb.2006.10.005.
59. Weng AP, Ferrando AA, Lee W, Morris JP 4th, Silverman LB, Sanchez-Irizarry C, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science. 2004; 306(5694): 269-271. doi: 10.1126/science.1102160.
60. Palomero T, Sulis ML, Cortina M, Real PJ, Barnes K, Ciofani M, et al. Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nat Med. 2007; 13(10): 1203-1210. doi: 10.1038/nm1636.
61. Herranz D, Ambesi-Impiombato A, Sudderth J, Sánchez-Martín M, Belver L, Tosello V, et al. Metabolic reprogramming induces resistance to anti- NOTCH1 therapies in T cell acute lymphoblastic leukemia. Nat Med. 2015; 21(10): 1182-1189. doi: 10.1038/nm.3955.
62. Palomero T, Wei KL, Odom DT, Sulis ML, Real PJ, Margolin A, et al. NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth. Proc Natl Acad Sci U S A. 2006;103(48):18261–6. doi: 10.1073/pnas.0606108103.
63. Weng AP, Millholland JM, Yashiro-Ohtani Y, Arcangeli ML, Lau A, Wai C, et al. c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma. Genes Dev. 2007; 21(5): 625. doi: 10.1101/gad.1450406.8.
64. Song K, Li M, Xu X, Xuan L, Huang G, Liu Q. Resistance to chemotherapy is associated with altered glucose metabolism in acute myeloid leukemia. Oncol Lett. 2016; 12(1): 334-342. doi: 10.3892/ol.2016.4600.
65. Beesley AH, Firth MJ, Ford J, Weller RE, Freitas JR, Perera KU, et al. Glucocorticoid resistance in T-lineage acute lymphoblastic leukaemia is associated with a proliferative metabolism. Br J Cancer. 2009; 100(12): 1926-1936. doi: 10.1038/ sj.bjc.6605072.
66. Holleman A, Cheok M, den Boer M, Yang W, Veerman A, Kazemier K, et al. Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment amy. N Engl J Med. 2004; 351(6): 533-542. doi: 10.1056/ NEJMoa033513.
67. Kluza J, Jendoubi M, Ballot C, Dammak A, Jonneaux A, Idziorek T, et al. Exploiting mitochondrial dysfunction for effective elimination of imatinib-resistant leukemic cells. PLoS One. 2011; 6(7): e21924. doi: 10.1371/journal.pone.0021924.
68. Zhao F, Mancuso A, Bui TV, Tong X, Gruber JJ, Swider CR, et al. Imatinib resistance associated with BCR-ABL upregulation is dependent on HIF-1α- induced metabolic reprograming. Oncogene. 2010; 29(20): 2962-2972. doi: 10.1038/onc.2010.67.
69. Herst PM, Howman RA, Neeson PJ, Berridge MV, Ritchie DS. The level of glycolytic metabolism in acute myeloid leukemia blasts at diagnosis is prognostic for clinical outcome. J Leukoc Biol. 2011; 89(1): 51-55. doi: 10.1189/jlb.0710417.
70. Schmitt S, Zischka H. Mitochondrien als potenzielle Zielstruktur in der Krebstherapie. Dtsch Zeitschrift Onkol. 2018; 50(3): 124-130. doi: 10.1055/a-0657-4437.
71. Kishton RJ, Barnes CE, Nichols AG, Cohen S, Gerriets VA, Siska PJ, et al. AMPK Is essential to balance glycolysis and mitochondrial metabolism to control T-ALL Cell stress and survival. Cell Metab. 2016; 23(4): 649-662. doi: 10.1016/j. cmet.2016.03.008.
72. Goto M, Miwa H, Suganuma K, Tsunekawa-Imai N, Shikami M, Mizutani M, et al. Adaptation of leukemia cells to hypoxic condition through switching the energy metabolism or avoiding the oxidative stress. BMC Cancer. 2014; 14(1): 1-9. doi: 10.1186/1471-2407-14-76.
73. Saito Y, Chapple RH, Lin A, Kitano A, Nakada D. AMPK Protects Leukemia-Initiating cells in myeloid leukemias from metabolic stress in the bone marrow. Cell Stem Cell. 2015; 17(5): 585-596. doi: 10.1016/j.stem.2015.08.019.
74. Blagih J, Coulombe F, Vincent EE, Dupuy F, Galicia-Vázquez G, Yurchenko E, et al. The energy sensor AMPK regulates t cell metabolic adaptation and effector responses in vivo. Immunity. 2015; 42(1): 41-54. doi: 10.1016/j.immuni.2014.12.030.
75. Pollyea DA, Gutman JA, Gore L, Smith CA, Jordan CT. targeting acute myeloid leukemia stem cells: a review and principles for the development of clinical trials. haematologica. 2014; 99(8): 1277-1284. doi: 10.3324/haematol.2013.085209.
76. Lane SW, Gilliland DG. Leukemia stem cells. Semin Cancer Biol. 2010; 20(2): 71-76. doi: 10.1016/j. semcancer.2009.12.001.
77. Kobune M, Takimoto R, Murase K, Iyama S, Sato T, Kikuchi S, et al. Drug resistance is dramatically restored by hedgehog inhibitors in CD34+ leukemic cells. Cancer Sci. 2009; 100(5): 948-955. doi: 10.1111/j.1349-7006.2009.01111.x.
78. Incardona JP, Gaffield W, Kapur RP, Roelink H. The teratogenic Veratrum alkaloid cyclopamine inhibits Sonic hedgehog signal transduction. Development. 1998; 125(18): 3553-3562.
79. Wahid M, Jawed A, Dar SA, Mandal RK, Haque S. Differential pharmacology and clinical utility of sonidegib in advanced basal cell carcinoma. Onco Targets Ther. 2017; 10: 515-520. doi: 10.2147/ OTT.S97713.
80. Schürch C, Riether C, Matter MS, Tzankov A, Ochsenbein AF. CD27 signaling on chronic myelogenous leukemia stem cells activates Wnt target genes and promotes disease progression. J Clin Invest. 2012; 122(2): 624-638. doi: 10.1172/ JCI45977.
81. Howard DS, Liesveld J, Phillips GL, Hayslip J, Weiss H, Jordan CT, et al. A phase I study using bortezomib with weekly idarubicin for treatment of elderly patients with acute myeloid leukemia. Leuk Res. 2013; 37(11): 1502-1508. doi: 10.1016/j. leukres.2013.09.003.
82. Horton T, Perentesis J, Gamis A, Alonzo T, Gerbing R, Ballard J, et al. A Phase 2 Study of bortezomib combined with either idarubicin/cytarabine or cytarabine/etoposide in children with relapsed, refractory or secondary acute myeloid leukemia: a report from the children’s Oncology Group. Pediatr Blood Cancer. 2014; 61(10): 1754-1760. doi: 10.1002/pbc.
83. Bonapace L, Bornhauser BC, Schmitz M, Cario G, Ziegler U, Niggli FK, et al. Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance. J Clin Invest. 2010; 120(4):1310-1323. doi: 10.1172/JCI39987.
84. Perl AE, Kasner MT, Tsai DE, Vogl DT, Loren AW, Schuster SJ, et al. A phase I study of the mammalian target of rapamycin inhibitor sirolimus and MEC chemotherapy in relapsed and refractory acute myelogenous leukemia. Clin Cancer Res. 2009; 15(21): 6732-6739. doi: 10.1158/1078-0432.CCR- 09-0842.
85. Krawczyk J, Keane N, Swords R, O’Dwyer M, Freeman CL, Giles FJ. Perifosine--a new option in treatment of acute myeloid leukemia? Expert Opin Investig Drugs. 2013; 22(10): 1315-1327. doi: 10.1517/13543784.2013.826648.
86. Akinleye A, Avvaru P, Furqan M, Song Y, Liu D. Phosphatidylinositol 3-kinase (PI3K) inhibitors as cancer therapeutics. J Hematol Oncol. 2013; 6: 1-17. doi: 10.1186/1756-8722-6-88.
87. Hulleman E, Kazemier KM, Holleman A, VanderWeele DJ, Rudin CM, Broekhuis MJC, et al. Inhibition of glycolysis modulates prednisolone resistance in acute lymphoblastic leukemia cells. Blood. 2009;113(9):2014–21. doi: 10.1182/ blood-2008-05-157842.
88. Samuels AL, Heng JY, Beesley AH, Kees UR. Bioenergetic modulation overcomes glucocorticoid resistance in T-lineage acute lymphoblastic leukaemia. Br J Haematol. 2014;165(1):57–66. doi: 10.1111/bjh.12727.
89. Liu H, Kurtoglu M, Cao Y, Xi H, Kumar R, Axten JM, et al. Conversion of 2-deoxyglucose-induced growth inhibition to cell death in normoxic tumor cells. Cancer Chemother Pharmacol. 2013;72(1):251–62. doi: 10.1007/s00280-013-2193-y.
90. Kurtoglu M, Gao N, Shang J, Maher JC, Lehrman MA, Wangpaichitr M, et al. Under normoxia, 2-deoxy-D-glucose elicits cell death in select tumor types not by inhibition of glycolysis but by interfering with N-linked glycosylation. Mol Cancer Ther. 2007;6(11):3049–58. doi: 10.1158/1535- 7163.MCT-07-0310.
91. Gu L, Yi Z, Zhang Y, Ma Z, Zhu Y, Gao J. Low dose of 2-deoxy-D-glucose kills acute lymphoblastic leukemia cells and reverses glucocorticoid resistance via N-linked glycosylation inhibition under normoxia. Oncotarget. 2017; 8(19): 30978-30991. Doi: 10.18632/oncotarget.16046.
92. Maschek G, Savaraj N, Priebe W, Braunschweiger P, Hamilton K, Tidmarsh GF, et al. 2-Deoxy-D-glucose Increases the Efficacy of Adriamycin and Paclitaxel in Human Osteosarcoma and Non-Small Cell Lung Cancers in Vivo. Cancer Res. 2004;64(1):31–4. doi: 10.1158/0008-5472.CAN-03-3294.
93. Nakano A, Tsuji D, Miki H, Cui Q, El Sayed SM, Ikegame A, et al. Glycolysis inhibition inactivates ABC transporters to restore drug sensitivity in malignant cells. PLoS One. 2011;6(11):1–10. doi: 10.1371/journal.pone.0027222.
94. Rosilio C, Ben-Sahra I, Bost F, Peyron JF. Metformin: A metabolic disruptor and anti-diabetic drug to target human leukemia. Cancer Lett. 2014;346(2):188–96. doi: 10.1016/j. canlet.2014.01.006.
95. Vakana E, Altman JK, Glaser H, Donato NJ, Platanias LC. Antileukemic effects of AMPK activators on BCR-ABL-expressing cells. Blood. 2011;118(24):6399–402. doi: 10.1182/ blood-2011-01-332783.
96. Pan J, Chen C, Jin Y, Fuentes-Mattei E, Velazquez- Tores G, Benito JM, et al. Differential impact of structurally different anti-diabetic drugs on proliferation and chemosensitivity of acute lymphoblastic leukemia cells. Cell Cycle. 2012;11(12):2314–26. doi: 10.4161/cc.20770.
97. Leclerc GM, Leclerc GJ, Kuznetsov JN, DeSalvo J, Barredo JC. Metformin Induces Apoptosis through AMPK-Dependent Inhibition of UPR Signaling in ALL Lymphoblasts. PLoS One. 2013;8(8):1–10. doi: 10.1371/journal.pone.0074420.
98. Santoyo-sánchez A, Jiménez-ponce F, Rozen-fuller E. Metformina adicionada a la quimioterapia contra la leucemia linfoblástica aguda. Rev del Inst Mex del Seguro Soc. 2014;52(3):270–5. Available from: https://www.medigraphic.com/pdfs/imss/im- 2014/im143i.pdf.
Creative Commons License
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.

Downloads

Não há dados estatísticos.