title: LMO2 expression reflects the different stages of blast maturation and genetic features in B-cell acute lymphoblastic leukemia and predicts clinical outcome.
abstract: BACKGROUND
  LMO2 is highly expressed at the most immature stages of lymphopoiesis. In T-lymphocytes, aberrant LMO2 expression beyond those stages leads to T-cell acute lymphoblastic leukemia, while in B cells LMO2 is also expressed in germinal center lymphocytes and diffuse large B-cell lymphomas, where it predicts better clinical outcome. The implication of LMO2 in B-cell acute lymphoblastic leukemia must still be explored.
  
  
  METHODS
  We measured LMO2 expression by real time RT-PCR in 247 acute lymphoblastic leukemia patient samples with cytogenetic data (144 of them also with survival and immunophenotypical data) and in normal hematopoietic and lymphoid cells.
  
  
  RESULTS
  B-cell acute lymphoblastic leukemia cases expressed variable levels of LMO2 depending on immunophenotypical and cytogenetic features. Thus, the most immature subtype, pro-B cells, displayed three-fold higher LMO2 expression than pre-B cells, common-CD10+ or mature subtypes. Additionally, cases with TEL-AML1 or MLL rearrangements exhibited two-fold higher LMO2 expression compared to cases with BCR-ABL rearrangements or hyperdyploid karyotype. Clinically, high LMO2 expression correlated with better overall survival in adult patients (5-year survival rate 64.8% (42.5%-87.1%) vs. 25.8% (10.9%-40.7%), P= 0.001) and constituted a favorable independent prognostic factor in B-ALL with normal karyotype: 5-year survival rate 80.3% (66.4%-94.2%) vs. 63.0% (46.1%-79.9%) (P= 0.043).
  
  
  CONCLUSIONS
  Our data indicate that LMO2 expression depends on the molecular features and the differentiation stage of B-cell acute lymphoblastic leukemia cells. Furthermore, assessment of LMO2 expression in adult patients with a normal karyotype, a group which lacks molecular prognostic factors, could be of clinical relevance.
authors: Division of Oncology, Center for Applied Medical Research (CIMA) University of Navarra, Pamplona, Spain.
authors: Raquel
authors: R
authors: Malumbres
authors: Vicente
authors: V
authors: Fresquet
authors: Jose
authors: J
authors: Roman-Gomez
authors: Miriam
authors: M
authors: Bobadilla
authors: Eloy F
authors: EF
authors: Robles
authors: Giovanna G
authors: GG
authors: Altobelli
authors: M José
authors: MJ
authors: Calasanz
authors: Erlend B
authors: EB
authors: Smeland
authors: Maria Angela
authors: MA
authors: Aznar
authors: Xabier
authors: X
authors: Agirre
authors: Vanesa
authors: V
authors: Martin-Palanco
authors: Felipe
authors: F
authors: Prosper
authors: Izidore S
authors: IS
authors: Lossos
authors: Jose A
authors: JA
authors: Martinez-Climent
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016175:B-Lymphocyte Subsets / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007621:Karyotyping; D060588:LIM Domain Proteins; D008667:Metalloproteins / Q000235:genetics*; D008875:Middle Aged; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D011379:Prognosis; D011518:Proto-Oncogene Proteins; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins