title: Constitutive AKT activation in follicular lymphoma.
abstract: BACKGROUND
  The phosphoinositide 3- kinase (PI3K) pathway is involved in the growth of various human cancers, including lymphoid malignancies. However its role in the pathogenesis of follicular lymphoma (FL) has not been yet described.
  
  
  METHODS
  To clarify this point, biopsy tissue samples from 38 human FL cases were investigated for PIK3CA somatic mutations in exon 9 and 20 using direct sequencing. The same samples were analyzed using western blotting and immunohistochemistry to detect expression of AKT, phosphorylated AKT (pAKT), and PTEN proteins. Two cases of benign lymphadenitis were used as controls.
  
  
  RESULTS
  AKT expression was present in all FL and lymphadenitis cases. 14/38 (37%) FL and 2/2 lymphadenitis cases expressed pAKT. 9/38 (24%) FL samples showed high level of pAKT, whereas 5/38 (13%) FL cases and 2/2 benign lymphadenitis samples expressed low level of pAKT. PTEN expression was observed in 30/38 (79%) FL and 2/2 benign lymphadenitis cases, whereas 8/38 (21%) FL cases showed loss of PTEN expression. 3 cases with positive pAKT did not express PTEN. PIK3CA mutations were not detected in any sample.
  
  
  CONCLUSIONS
  These data suggest that the PI3K/AKT signaling pathway could be activated in a subset of FL cases, due to either AKT phosphorylation or PTEN downregulation, in the absence of PIK3CA mutations.
authors.affiliation: Inserm, U1068, Centre de Recherche en Cancérologie de Marseille, Marseille, France. imene.yahiaoui@inserm.fr.
authors.forename: Ouardia I
authors.initials: OI
authors.lastname: Yahiaoui
authors.forename: Jacques A
authors.initials: JA
authors.lastname: Nunès
authors.forename: Céline
authors.initials: C
authors.lastname: Castanier
authors.forename: Raynier
authors.initials: R
authors.lastname: Devillier
authors.forename: Florence
authors.initials: F
authors.lastname: Broussais
authors.forename: Aurélie J
authors.initials: AJ
authors.lastname: Fabre
authors.forename: Dalila
authors.initials: D
authors.lastname: Naimi
authors.forename: Réda
authors.initials: R
authors.lastname: Bouabdallah
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
authors.forename: Luc
authors.initials: L
authors.lastname: Xerri
mesh_terms: D000328:Adult; D000368:Aged; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
references.citation: Int J Cancer. 1995 Aug 22;64(4):280-5
references.pmid: 7657393
references.citation: Sci Signal. 2009 Sep 01;2(86):pl3
references.pmid: 19724061
references.citation: Leukemia. 2003 May;17(5):995-7
references.pmid: 12750723
references.citation: Science. 2002 May 31;296(5573):1655-7
references.pmid: 12040186
references.citation: Apoptosis. 2004 Nov;9(6):667-76
references.pmid: 15505410
references.citation: Science. 2004 Apr 23;304(5670):554
references.pmid: 15016963
references.citation: Int J Cancer. 2005 Mar 20;114(2):242-8
references.pmid: 15543611
references.citation: Leukemia. 2010 Oct;24(10):1781-4
references.pmid: 20703254
references.citation: Oncogene. 2000 May 25;19(23):2739-44
references.pmid: 10851074
references.citation: Curr Opin Oncol. 2006 Jan;18(1):77-82
references.pmid: 16357568
references.citation: Lab Invest. 2004 Feb;84(2):235-44
references.pmid: 14767488
references.citation: Annu Rev Pathol. 2009;4:127-50
references.pmid: 18767981
references.citation: Cell Cycle. 2004 Oct;3(10):1221-4
references.pmid: 15467468
references.citation: Mol Cell. 2005 Apr 1;18(1):13-24
references.pmid: 15808505
references.citation: Clin Cancer Res. 2005 Aug 15;11(16):5847-55
references.pmid: 16115925
references.citation: J Immunol. 2009 Jun 15;182(12):7681-9
references.pmid: 19494292
references.citation: Leukemia. 2006 Feb;20(2):374-6
references.pmid: 16341041
references.citation: Clin Cancer Res. 2009 Sep 15;15(18):5724-32
references.pmid: 19723646
references.citation: Cancer Res. 2004 Nov 1;64(21):7678-81
references.pmid: 15520168
references.citation: Nat Rev Cancer. 2002 Jul;2(7):489-501
references.pmid: 12094235
references.citation: Leukemia. 2007 Nov;21(11):2368-70
references.pmid: 17657213
references.citation: Exp Cell Res. 1999 Nov 25;253(1):239-54
references.pmid: 10579926
references.citation: Adv Cancer Res. 2005;94:29-86
references.pmid: 16095999
references.citation: Expert Opin Investig Drugs. 2012 Jan;21(1):15-22
references.pmid: 22112004
references.citation: J Biol Chem. 1997 Aug 1;272(31):19236-41
references.pmid: 9235916
references.citation: J Exp Med. 2002 Sep 16;196(6):753-63
references.pmid: 12235209
references.citation: J Hematol Oncol. 2013 Aug 02;6:55
references.pmid: 23915913
references.citation: Am J Respir Crit Care Med. 2004 Nov 15;170(10):1088-94
references.pmid: 15317667
references.citation: Blood. 2006 Sep 1;108(5):1668-76
references.pmid: 16645163
references.citation: Nat Rev Cancer. 2005 Dec;5(12):921-9
references.pmid: 16341083
references.citation: Hematology Am Soc Hematol Educ Program. 2009;:523-31
references.pmid: 20008237
references.citation: Brain Pathol. 2003 Oct;13(4):507-18
references.pmid: 14655756
references.citation: Blood. 2011 Jan 13;117(2):591-4
references.pmid: 20959606
references.citation: Adv Cancer Res. 2009;102:19-65
references.pmid: 19595306
references.citation: Blood. 2006 Dec 15;108(13):4178-86
references.pmid: 16946303
references.citation: Nature. 2007 Jul 26;448(7152):439-44
references.pmid: 17611497
references.citation: J Clin Oncol. 2011 May 10;29(14):1803-11
references.pmid: 21483013
references.citation: J Natl Cancer Inst. 1999 Nov 17;91(22):1922-32
references.pmid: 10564676
references.citation: Leukemia. 2002 May;16(5):894-901
references.pmid: 11986952
references.citation: Nat Rev Genet. 2006 Aug;7(8):606-19
references.pmid: 16847462
references.citation: Int J Cancer. 2003 Apr 10;104(3):318-27
references.pmid: 12569555
references.citation: Cancer Res. 2001 Oct 15;61(20):7426-9
references.pmid: 11606375