The level of AKT phosphorylation on threonine 308 but not on serine 473 is associated with high-risk cytogenetics and predicts poor overall survival in acute myeloid leukaemia

Leukemia

Volumn 23, Issue 6, 2009, Pages 1029-1038

  Gallay, N ^a,b   Dos Santos, C ^a,b   Cuzin, L ^c   Bousquet, M ^a,b   Gouy, V Simmonet ^c   Chaussade, C ^d   Attal, M ^c   Payrastre, B ^a,b,c   Demur, C ^a,b,c   Recher C ^a,b,c  

^a France   (France)

^b UNIVERSITÉ DE TOULOUSE   (France)

^c CHU PURPAN   (France)

^d UNIVERSITY OF AUCKLAND   (New Zealand)

Author keywords

[No Author keywords available]

Indexed keywords

CD123 ANTIGEN; CD135 ANTIGEN; CD34 ANTIGEN; CD38 ANTIGEN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PHOSPHOINOSITIDE DEPENDENT PROTEIN KINASE 1; PHOSPHOPROTEIN PHOSPHATASE 2A; PROTEIN KINASE B; PROTEIN KINASE B INHIBITOR; SERINE; THREONINE;

ACUTE GRANULOCYTIC LEUKEMIA; ADOLESCENT; ADULT; APOPTOSIS; ARTICLE; CANCER MORPHOLOGY; CANCER RISK; CANCER SURVIVAL; CELL PROLIFERATION; CONTROLLED STUDY; CYTOGENETICS; DISEASE FREE SURVIVAL; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; EVENT FREE SURVIVAL; FEMALE; FLUORESCENCE ANALYSIS; GENE MUTATION; GENETIC RISK; HUMAN; HUMAN CELL; KARYOTYPE; LEUKEMIA CELL LINE; LEUKOCYTE COUNT; LEUKOCYTOSIS; MALE; MUTATIONAL ANALYSIS; OVERALL SURVIVAL; PRIORITY JOURNAL; PROGNOSIS; PROTEIN EXPRESSION; SURVIVAL TIME;

EID: 67349180268     PISSN: 08876924     EISSN: 14765551     Source Type: Journal    
DOI: 10.1038/leu.2008.395     Document Type: Article

References (46)

1. Cully M, You H, Levine AJ, Mak TW. Beyond PTEN mutations: The PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer 2006; 6: 184-192.
2. Vanhaesebroeck B, Alessi DR. The PI3K-PDK1 connection: More than just a road to PKB. Biochem J 2000; 346: 561-576.
3. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005; 307: 1098-1101.
4. Martelli AM, Nyåkern M, Tabellini G, Bortul R, Tazzari PL, Evangelisti C et al. Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia. Leukemia 2006; 20: 911-928.
5. Min YH, Eom JI, Cheong JW, Maeng HO, Kim JY, Jeung HK et al. Constitutive phosphorylation of Akt/PKB protein in acute myeloid leukemia: Its significance as a prognostic variable. Leukemia 2003; 17: 995-997.
6. Kornblau SM, Womble M, Qiu YH, Jackson CE, Chen W, Konopleva M et al Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia. Blood 2006; 108: 2358-2365.
7. Tamburini J, Elie C, Bardet V, Chapuis N, Park S, Broët P et al Constitutive phosphoinositide 3-kinase/Akt activation represents a favorable prognostic factor in de novo acute myelogenous leukemia patients. Blood 2007; 110: 1025-1028.
8. Tazzari PL, Cappellini A, Grafone T, Mantovani I, Ricci F, Billi AM et al. Detection of serine 473 phosphorylated Akt in acute myeloid leukaemia blasts by flow cytometry. Br J Haematol 2004; 126: 675-681.
9. Bardet V, Tamburini J, Ifrah N, Dreyfus F, Mayneux P, Bouscary D et al. Single cell analysis of phosphoinositide 3-kinase/Akt and ERK activation in acute myeloid leukemia by flow cytometry. Haematologica 2006; 91: 757-764.
10. Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: A Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 2000; 96: 4075-4083.
11. Zhao Z, Leister WH, Robinson RG, Barnett SF, Defeo-Jones D, Jones RE et al. Discovery of 2,3,5-trisubstituted pyridine derivatives as potent Akt1 and Akt2 dual inhibitors. Bioorg Med Chem Lett 2005; 15: 905-909.
12. Bousquet M, Le Guellec S, Quelen C, Rigal-Huguet F, Delsol G, Brousset P. Frequent detection of the JAK2 V617F mutation in bone marrow core biopsy specimens from chronic myeloproliferative disorders using the TaqMan polymerase chain reaction single nucleotide polymorphism genotyping assay: A retrospective study with pathologic correlations. Hum Pathol 2006; 37: 1458-1464.
13. Quentmeier H, Zaborski M, Drexler HG. The human bladder carcinoma cell line 5637 constitutively secretes functional cytokines. Leuk Res 1997; 21: 343-350.
14. Dos Santos C, Demur C, Bardet V, Prade-Houdellier N, Payrastre B, Récher C. A critical role for Lyn in acute myeloid leukemia. Blood 2008; 111: 2269-2279.
15. Bousquet M, Récher C, Queleen C, Demur C, Payrastre B, Brousset P. Assessment of somatic mutations in phosphatidylinositol 3-kinase gene in human lymphoma and acute leukaemia. Br J Haematol 2005; 131: 411-413.
16. Cornillet-Lefebvre P, Cuccuini W, Bardet V, Tamburini J, Gillot L, Ifrah N et al. Constitutive phosphoinositide 3-kinase activation in acute myeloid leukemia is not due to p110delta mutations. Leukemia 2006; 20: 374-376.
17. Carpten JD, Faber AL, Horn C, Donoho GP, Briggs SL, Robbins CM et al A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature 2007; 448: 439-444.
18. Tibes R, Kornblau SM, Qiu Y, Mousses SM, Robbins C, Moses T et al. PI3K/AKT pathway activation in acute myeloid leukaemias is not associated with AKT1 pleckstrin homology domain mutation. Br J Haematol 2008; 140: 344-347.
19. Zenz T, Döhner K, Denzel T, Döhner H, Stilgenbauer S, Bullinger L. Chronic lymphocytic leukaemia and acute myeloid leukaemia are not associated with AKT1 pleckstrin homology domain (E17K) mutations. Br J Haematol 2008; 141: 742-743.
20. Lian Z, Di Cristofano A. Class reunion: PTEN joins the nuclear crew. Oncogene 2005; 24: 7394-7400.
21. Liu TC, Lin PM, Chang JG, Lee JP, Chen TP, Lin SF. Mutation analysis of PTEN/MMAC1 in acute myeloid leukemia. Am J Hematol 2000; 63: 170-175.
22. Georgescu MM, Kirsch KH, Akagi T, Shishido T, Hanafusa H. The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region. Proc Natl Acad Sci USA 1999; 96: 10182-10187.
23. Vazquez F, Ramaswamy S, Nakamura N, Sellers WR. Phosphorylation of the PTEN tail regulates protein stability and function. Mol Cell Biol 2000; 20: 5010-5018.
24. Cheong JW, Eom JI, Maeng HY, Lee ST, Hahn JS, Ko YW et al. Phosphatase and tensin homologue phosphorylation in the C-terminal regulatory domain is frequently observed in acute myeloid leukaemia and associated with poor clinical outcome. Br J Haematol 2003; 122 454-456.
25. Millward TA, Zolnierowicz S, Hemmings BA. Regulation of protein kinase cascades by protein phosphatase 2A. Trends Biochem Sci 1999; 24 186-191.
26. Neviani P, Santhanam R, Oaks JJ, Eiring AM, Notari M, Blaser BW et al FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia. J Clin Invest 2007; 117: 2408-2421.
27. Papa V, Tazzari PL, Chiarini F, Cappellini A, Ricci F, Billi AM et al Proapoptotic activity and chemosensitizing effect of the novel Akt inhibitor perifosine in acute myelogenous leukemia cells. Leukemia 2008; 22: 147-160.
28. Cheng JQ, Lindsley CW, Cheng GZ, Yang H, Nicosia SV. The Akt/PKB pathway: Molecular target for cancer drug discovery. Oncogene 2005; 24: 7482-7492.
29. Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H et al The selectivity of protein kinase inhibitors: A further update. Biochem J 2007; 408: 297-315.
30. Beyne-Rauzy O, Récher C, Dastugue N, Demur C, Pottier G, Laurent G et al. Tumor necrosis factor alpha induces senescence and chromosomal instability in human leukemic cells. Oncogene 2004; 23: 7507-7516.
31. Jordan CT, Guzman ML. Mechanisms controlling pathogenesis and survival of leukemic stem cells. Oncogene 2004; 23: 7178-7187.
32. 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: 1315-1321.
33. Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 2006; 7: 606-619.
34. Gao T, Furnari F, Newton AC. PHLPP: A phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth. Mol Cell 2005; 18: 13-24.
35. Adachi Y, Pavlakis GN, Copeland TD. Identification and characterization of SET, a nuclear phosphoprotein encoded by the translocation break point in acute undifferentiated leukemia. J Biol Chem 1994; 269 2258-2262.
36. Adler HT, Nallaseth FS, Walter G, Tkachuk DC. HRX leukemic fusion proteins form a heterocomplex with the leukemia-associated protein SET and protein phosphatase 2A. J Biol Chem 1997; 272: 28407-28414.
37. Toker A, Newton AC. Cellular signaling: Pivoting around PDK-1. Cell 2000; 103: 185-188.
38. Stokoe D, Stephens LR, Copeland T, Gaffney PR, Reese CB, Painter GF et al. Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. Science 1997; 277: 567-570.
39. Pearn L, Fisher J, Burnett AK, Darley RL. The role of PKC and PDK1 in monocyte lineage specification by Ras. Blood 2007; 109: 4461-4469.
40. Xu Q, Simpson SE, Scialla TJ, Bagg A, Carroll M. Survival of acute myeloid leukemia cells requires PI3 kinase activation. Blood 2003; 102: 972-980.
41. Grandage VL, Gale RE, Linch DC, Khwaja A. PI3-kinase/Akt is constitutively active in primary acute myeloid leukaemia cells and regulates survival and chemoresistance via NF-kappaB, Mapkinase and p53 pathways. Leukemia 2005; 19: 586-594.
42. Harris SL, Levine AJ. The p53 pathway: Positive and negative feedback loops. Oncogene 2005; 24: 2899-2908.
43. Tsurutani J, Fukuoka J, Tsurutani H, Shih JH, Hewitt SM, Travis WD et al. Evaluation of two phosphorylation sites improves the prognostic significance of Akt activation in non-small-cell lung cancer tumors. J Clin Oncol 2006; 24: 306-314.
44. Jacinto E, Facchinetti V, Liu D, Soto N, Wei S, Jung SY et al. SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrates. Cell 2006; 127: 125-137.
45. Park S, Chapuis N, Bardet V, Tamburini J, Gallay N, Willems L et al PI-103, a dual inhibitor of class IA phosphatidylinositide 3-kinase and mTOR, has antileukemic activity in AML. Leukemia 2008; 22 1698-1706.
46. Guzman ML, Rossi RM, Neelakantan S, Li X, Corbett CA, Hassane DC et al. An orally bioavailable parthenolide analog selectively eradicates acute myelogenous leukemia stem and progenitor cells. Blood 2007; 110: 4427-4435.