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Survival of acute myeloid leukemia cells requires PI3 kinase activation

Xu, Qing, Simpson, Serge-Emile, Scialla, Timothy J., Bagg, Adam, Carroll, Martin·2003·Blood
DOI 10.1182/blood-2002-11-3429
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Abstract

The mechanisms that regulate the growth and survival of acute myeloid leukemia (AML) cells are largely unknown. We hypothesized that constitutive activation of phosphatidyl-inositide 3 kinase (PI3 kinase) could regulate survival in primary cells from patients with AML. Here we demonstrate that Akt, a critical substrate of PI3 kinase, is activated in AML blasts. In a short-term culture system, most AML patient samples showed a dose-dependent decrease in survival after incubation with the PI3 kinase inhibitor LY294002. This decrease in survival was partially due to the induction of apoptosis. Furthermore, we have shown that p70 S6 kinase and 4EBP-1, downstream mediators of Akt signaling, also are phosphorylated in AML blasts. Phosphorylation of these proteins is inhibited by the mTOR inhibitor RAD001. Incubation of AML blasts with RAD001 induces only a small decrease in survival of the cells; however, when combined with Ara-C, RAD001 enhances the toxicity of Ara-C. These results demonstrate that constitutive activation of the PI3 kinase pathway is necessary for the survival of AML blasts and that targeting of this pathway with pharmacologic inhibitors may be of clinical benefit in treatment of AML.

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Research works printed but not linked: 43

  1. Rowley JD. The role of chromosome translocations in leukemogenesis. Semin Hematol.1999;36: 59-72.
  2. Look AT. Oncogenic transcription factors in the human acute leukemias. Science. 1997;278: 1059-1064. · DOI
  3. Castilla LH, Garrett L, Adya N, et al. The fusion gene Cbfb-MYH11 blocks myeloid differentiation and predisposes mice to acute myelomonocytic leukaemia. Nat Genet.1999;23: 144-146. · DOI
  4. Rhoades KL, Hetherington CJ, Harakawa N, et al. Analysis of the role of AML1-ETO in leukemogenesis, using an inducible transgenic mouse model. Blood. 2000;96: 2108-2115. · DOI
  5. He L, Bhaumik M, Tribioli C, et al. Two critical hits for promyelocytic leukemia. Mol Cell. 2000;6: 1131-1141. · DOI
  6. He LZ, Tribioli C, Rivi R, et al. Acute leukemia with promyelocytic features in PML/RARalpha transgenic mice. Proc Natl Acad Sci U S A. 1997;94: 5302-5307. · DOI
  7. Yuan Y, Zhou L, Miyamoto T, et al. AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations. Proc Natl Acad Sci U S A. 2001;98: 10398-10403. · DOI
  8. Nakao M, Yokota S, Iwai T, et al. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia. 1996;10: 1911-1918.
  9. Abu-Duhier FM, Goodeve AC, Wilson GA, et al. FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group. Br J Haematol.2000;111: 190-195. · DOI
  10. Carow CE, Levenstein M, Kaufmann SH, et al. Expression of the hematopoietic growth factor receptor FLT3 (STK-1/Flk2) in human leukemias. Blood. 1996;87: 1089-1096. · DOI
  11. Levis M, Tse KF, Smith BD, Garrett E, Small D. A FLT3 tyrosine kinase inhibitor is selectively cytotoxic to acute myeloid leukemia blasts harboring FLT3 internal tandem duplication mutations. Blood. 2001;98: 885-887. · DOI
  12. Dash A, Gilliland DG. Molecular genetics of acute myeloid leukaemia. Best Pract Res Clin Haematol.2001;14: 49-64. · DOI
  13. Kelly LM, Kutok JL, Williams IR, et al. PML/RARalpha and FLT3-ITD induce an APL-like disease in a mouse model. Proc Natl Acad Sci U S A. 2002;99: 8283-8288. · DOI
  14. Gouilleux-Gruart V, Gouilleux F, Desaint C, et al. STAT-related transcription factors are constitutively activated in peripheral blood cells from acute leukemia patients. Blood. 1996;87: 1692-1697. · DOI · Paper page
  15. Xia Z, Baer MR, Block AW, Baumann H, Wetzler M. Expression of signal transducers and activators of transcription proteins in acute myeloid leukemia blasts. Cancer Res.1998;58: 3173-3180.
  16. Towatari M, Iida H, Tanimoto M, Iwata H, Hamaguchi M, Saito H. Constitutive activation of mitogen-activated protein kinase pathway in acute leukemia cells. Leukemia. 1997;11: 479-484. · DOI
  17. Kim SC, Hahn JS, Min YH, Yoo NC, Ko YW, Lee WJ. Constitutive activation of extracellular signal-regulated kinase in human acute leukemias: combined role of activation of MEK, hyperexpression of extracellular signal-regulated kinase, and downregulation of a phosphatase, PAC1. Blood. 1999;93: 3893-3899. · DOI
  18. Milella M, Kornblau SM, Estrov Z, et al. Therapeutic targeting of the MEK/MAPK signal transduction module in acute myeloid leukemia. J Clin Invest.2001;108: 851-859. · DOI
  19. Guzman ML, Swiderski CF, Howard DS, et al. Preferential induction of apoptosis for primary human leukemic stem cells. Proc Natl Acad Sci U S A. 2002;99: 16220-16225. · DOI
  20. Guzman ML, Neering SJ, Upchurch D, et al. Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells. Blood. 2001;98: 2301-2307. · DOI
  21. Corvera S, Czech MP. Direct targets of phosphoinositide 3-kinase products in membrane traffic and signal transduction. Trends Cell Biol.1998;8: 442-446. · DOI
  22. Beslu N, LaRose J, Casteran N, et al. Phosphatidylinositol-3′ kinase is not required for mitogenesis or internalization of the Flt3/Flk2 receptor tyrosine kinase. J Biol Chem.1996;271: 20075-20081. · DOI
  23. Dosil M, Wang S, Lemischka IR. Mitogenic signalling and substrate specificity of the Flk2/Flt3 receptor tyrosine kinase in fibroblasts and interleukin 3-dependent hematopoietic cells. Mol Cell Biol.1993;13: 6572-6585. · DOI
  24. Coffer PJ, Woodgett JR. Molecular cloning and characterisation of a novel putative protein-serine kinase related to the cAMP-dependent and protein kinase C families. Eur J Biochem.1991;201: 475-481. · DOI
  25. Staal SP. Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma. Proc Natl Acad Sci U S A. 1987;84: 5034-5037. · DOI
  26. Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer. 2002;2: 489-501. · DOI
  27. Wu X, Senechal K, Neshat MS, Whang YE, Sawyers CL. The PTEN/MMAC1 tumor suppressor phosphatase functions as a negative regulator of the phosphoinositide 3-kinase/Akt pathway. Proc Natl Acad Sci U S A. 1998;95: 15587-15591. · DOI · Paper page
  28. Kiyoi H, Naoe T, Yokota S, et al. Internal tandem duplication of FLT3 associated with leukocytosis in acute promyelocytic leukemia: Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho). Leukemia. 1997;11: 1447-1452. · DOI
  29. Yamamoto Y, Kiyoi H, Nakano Y, et al. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood. 2001;97: 2434-2439. · DOI
  30. Majka M, Ratajczak J, Villaire G, et al. Thrombopoietin, but not cytokines binding to gp130 protein-coupled receptors, activates MAPKp42/44, AKT, and STAT proteins in normal human CD34+ cells, megakaryocytes, and platelets. Exp Hematol.2002;30: 751-760. · DOI
  31. Vlahos CJ, Matter WF, Brown RF, et al. Investigation of neutrophil signal transduction using a specific inhibitor of phosphatidylinositol 3-kinase. J Immunol.1995;154: 2413-2422. · DOI
  32. Vlahos CJ, Matter WF, Hui KY, Brown RF. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J Biol Chem.1994;269: 5241-5248. · DOI
  33. Dierov J, Xu Q, Dierova R, Carroll M. TEL/PDGF-betaR activates PI3 kinase and requires PI3 kinase for regulation of the cell cycle. Blood. 2002;99: 1758-1765. · DOI
  34. Craddock BL, Orchiston EA, Hinton HJ, Welham MJ. Dissociation of apoptosis from proliferation, protein kinase B activation, and BAD phosphorylation in interleukin-3-mediated phosphoinositide 3-kinase signaling. J Biol Chem.1999;274: 10633-10640. · DOI
  35. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med.1997;3: 730-737. · DOI · Paper page
  36. Nashan B. The role of Certican (everolimus, rad) in the many pathways of chronic rejection. Transplant Proc.2001;33: 3215-3220. · DOI
  37. Podsypanina K, Lee RT, Politis C, et al. An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice. Proc Natl Acad Sci U S A. 2001;98: 10320-10325. · DOI
  38. Neshat MS, Mellinghoff IK, Tran C, et al. Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc Natl Acad Sci U S A. 2001;98: 10314-10319. · DOI
  39. Dahia P, Aguiar R, Alberta J, et al. PTEN is inversely correlated with the cell survival factor Akt/PKB and is inactivated via multiple mechanisms in haematological malignancies. Hum Mol Genet.1999;8: 185-193. · DOI
  40. Huber M, Helgason CD, Damen JE, et al. The role of SHIP in growth factor induced signalling. Prog Biophys Mol Biol.1999;71: 423-434. · DOI
  41. Geier SJ, Algate PA, Carlberg K, et al. The human SHIP gene is differentially expressed in cell lineages of the bone marrow and blood. Blood. 1997;89: 1876-1885. · DOI
  42. Horn S, Meyer J, Heukeshoven J, et al. The inositol 5-phosphatase SHIP is expressed as 145 and 135 kDa proteins in blood and bone marrow cells in vivo, whereas carboxyl-truncated forms of SHIP are generated by proteolytic cleavage in vitro. Leukemia. 2001;15: 112-120. · DOI
  43. Leslie NR, Downes CP. PTEN: the down side of PI 3-kinase signalling. Cell Signal. 2002;14: 285-295. · DOI · Paper page

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Metadata

Authors
Xu, Q., Simpson, S.-E., Scialla, T. J., Bagg, A., & Carroll, M.
Venue
Blood
Publisher
American Society of Hematology
Published
2003-08-01
Volume
102
Issue
3
Pages
972-980
ISSN
  • 0006-4971
  • 1528-0020
DOI
10.1182/blood-2002-11-3429
Cited by
394
References
2
Language
en

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