LMO2 expression reflects the different stages of blast maturation and genetic features in B-cell acute lymphoblastic leukemia and predicts clinical outcome

Haematologica. 2011 Jul;96(7):980-6. doi: 10.3324/haematol.2011.040568. Epub 2011 Apr 1.

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.

Design and 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • B-Lymphocyte Subsets / metabolism
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Child
  • Child, Preschool
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Immunophenotyping
  • Infant
  • Karyotyping
  • LIM Domain Proteins
  • Metalloproteins / genetics*
  • Middle Aged
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Prognosis
  • Proto-Oncogene Proteins
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • LIM Domain Proteins
  • LMO2 protein, human
  • Metalloproteins
  • Proto-Oncogene Proteins