title: Proteomic profile of pre - B2 lymphoblasts from children with acute lymphoblastic leukemia (ALL) in relation with the translocation (12; 21).
abstract: BACKGROUND
  Until now, the major prognostic factors for pediatric acute lymphoblastic leukemia (ALL), age, white blood cell count and chromosomal alterations are initially taken into account for the risk stratification of patients. In the light of protein marker studies to classify subtypes of Acute Myeloblastic Leukemia efficiently, we have compared the lymphoblastes proteome in Childhood ALL in accordance with the presence of t(12;21), indicator of good prognosis, usually.
  
  
  METHODS
  Protein expression in pre-B2 lymphoblastic cells, collected from residual bone marrow cells after diagnostic procedures, was analyzed using two dimensional gel electrophoresis protocol. Protein spots whose average normalized volumes were statistically different in the two patients groups (n = 13; student t test p < 0.01), were excised. Tryptic peptides were then analyzed using a nano-LC1200 system coupled to a 6340 Ion Trap mass spectrometer equipped with a HPLC-chip cube interface. The tandem mass spectrometry peak lists extracted using the DataAnalysis program, were compared with the protein database Mascot Daemon.
  
  
  RESULTS
  We focused on twelve spots corresponding to sixteen identified candidate proteins among the 26 found differentially expressed (p ≤ 0.05) regarding the presence of t(12;21). Among over expressed proteins, two proteins were implicated in cellular growth arrest (i.e. calponine 2, p ≤ 0.001 and phosphatidylinositol transfer protein beta, p ≤ 0.001) in accordance with good prognosis, while two other proteins favored cell cycle proliferation (i.e. methionine adenosyl transferase 2β, p ≤ 0.005 and heterogeneous nuclear ribonucleo-proteins A2 p ≤ 0.01) and could therefore be good marker candidates of aggressiveness. Level of expression of proteasome subunit beta type-2 (p ≤ 0.01) and protein casein kinase 2α (p ≤ 0.01) which both favored apoptosis, deubiquitinating enzyme OTUB1 (p ≤ 0.05) and MLL septin-like fusion protein MSF-B, septin 9 i4 (p ≤ 0.01) were in accord with a good prognosis related to t(12;21) lymphoblasts.
  
  
  CONCLUSIONS
  By drawing up the protein map of leukemic cells, these new data identified marker candidates of leukemic aggressiveness and new t(12;21) patients subgroups. These preliminary results will be in the near future confirmed by using a larger sample of pre-B2 childhood ALLs from national lymphoblastic cell collections.
authors.affiliation: Laboratoire MERCI, Faculté de Médecine et de Pharmacie de Rouen, 123 boulevard Gambetta, Rouen, Cedex 76183, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Costa
authors.affiliation: Laboratoire MERCI, Faculté de Médecine et de Pharmacie de Rouen, 123 boulevard Gambetta, Rouen, Cedex 76183, France ; Service d'Immuno-Hématologie Onco-pédiatrique du CHRU de Rouen, Hôpital Charles Nicolle, Rouen 76031, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Schneider
authors.affiliation: PISSARO Proteomic facility, (IRIB), U-Rouen, Mont Saint- Aignan, France ; CNRS UMR 6270, Team « Biofilms, Résistance, Interactions Cellules-Surfaces », U-Rouen, Mont Saint-Aignan, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Coquet
authors.affiliation: PISSARO Proteomic facility, (IRIB), U-Rouen, Mont Saint- Aignan, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Chan
authors.affiliation: Laboratoire de Cytogénétique, Centre Henri Becquerel, Rouen 76000, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Penther
authors.affiliation: Laboratoire MERCI, Faculté de Médecine et de Pharmacie de Rouen, 123 boulevard Gambetta, Rouen, Cedex 76183, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Legrand
authors.affiliation: PISSARO Proteomic facility, (IRIB), U-Rouen, Mont Saint- Aignan, France ; CNRS UMR 6270, Team « Biofilms, Résistance, Interactions Cellules-Surfaces », U-Rouen, Mont Saint-Aignan, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Jouenne
authors.affiliation: Laboratoire MERCI, Faculté de Médecine et de Pharmacie de Rouen, 123 boulevard Gambetta, Rouen, Cedex 76183, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Vasse
authors.affiliation: Laboratoire MERCI, Faculté de Médecine et de Pharmacie de Rouen, 123 boulevard Gambetta, Rouen, Cedex 76183, France ; Service d'Immuno-Hématologie Onco-pédiatrique du CHRU de Rouen, Hôpital Charles Nicolle, Rouen 76031, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vannier
keywords: Biomarkers; Calponin; Childhood ALL; OTUB1; Protein casein kinase CK2α and Ikaros