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

Raquel Malumbres, Vicente Fresquet, Jose Roman-Gomez, Miriam Bobadilla, Eloy F. Robles, Giovanna G. Altobelli, M. José Calasanz, Erlend B. Smeland, Maria Angela Aznar, Xabier Agirre, Vanesa Martin-Palanco, Felipe Prosper, Izidore S. Lossos, Jose A. Martinez-Climents

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)980-986
Number of pages7
JournalHaematologica
Volume96
Issue number7
DOIs
StatePublished - Jul 2011

Keywords

  • Acute leukemia
  • B lymphocytes
  • Gene expression
  • Prognostic factor

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'LMO2 expression reflects the different stages of blast maturation and genetic features in B-cell acute lymphoblastic leukemia and predicts clinical outcome'. Together they form a unique fingerprint.

  • Cite this

    Malumbres, R., Fresquet, V., Roman-Gomez, J., Bobadilla, M., Robles, E. F., Altobelli, G. G., Calasanz, M. J., Smeland, E. B., Aznar, M. A., Agirre, X., Martin-Palanco, V., Prosper, F., Lossos, I. S., & Martinez-Climents, J. A. (2011). LMO2 expression reflects the different stages of blast maturation and genetic features in B-cell acute lymphoblastic leukemia and predicts clinical outcome. Haematologica, 96(7), 980-986. https://doi.org/10.3324/haematol.2011.040568