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 Lossos, Jose A. Martinez-Climents

Research output: Contribution to journalArticle

19 Citations (Scopus)

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
Pages (from-to)980-986
Number of pages7
JournalHaematologica
Volume96
Issue number7
DOIs
StatePublished - Jul 1 2011

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
B-Lymphocytes
Karyotype
B-Lymphoid Precursor Cells
Cytogenetics
Survival Rate
Lymphocytes
Lymphopoiesis
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Germinal Center
Survival
Lymphoma, Large B-Cell, Diffuse
Real-Time Polymerase Chain Reaction
T-Lymphocytes

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

Malumbres, R., Fresquet, V., Roman-Gomez, J., Bobadilla, M., Robles, E. F., Altobelli, G. G., ... 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

LMO2 expression reflects the different stages of blast maturation and genetic features in B-cell acute lymphoblastic leukemia and predicts clinical outcome. / Malumbres, Raquel; Fresquet, Vicente; Roman-Gomez, Jose; Bobadilla, Miriam; Robles, Eloy F.; Altobelli, Giovanna G.; Calasanz, M. José; Smeland, Erlend B.; Aznar, Maria Angela; Agirre, Xabier; Martin-Palanco, Vanesa; Prosper, Felipe; Lossos, Izidore; Martinez-Climents, Jose A.

In: Haematologica, Vol. 96, No. 7, 01.07.2011, p. 980-986.

Research output: Contribution to journalArticle

Malumbres, R, Fresquet, V, Roman-Gomez, J, Bobadilla, M, Robles, EF, Altobelli, GG, Calasanz, MJ, Smeland, EB, Aznar, MA, Agirre, X, Martin-Palanco, V, Prosper, F, Lossos, I & Martinez-Climents, JA 2011, 'LMO2 expression reflects the different stages of blast maturation and genetic features in B-cell acute lymphoblastic leukemia and predicts clinical outcome', Haematologica, vol. 96, no. 7, pp. 980-986. https://doi.org/10.3324/haematol.2011.040568
Malumbres, Raquel ; Fresquet, Vicente ; Roman-Gomez, Jose ; Bobadilla, Miriam ; Robles, Eloy F. ; Altobelli, Giovanna G. ; Calasanz, M. José ; Smeland, Erlend B. ; Aznar, Maria Angela ; Agirre, Xabier ; Martin-Palanco, Vanesa ; Prosper, Felipe ; Lossos, Izidore ; Martinez-Climents, Jose A. / LMO2 expression reflects the different stages of blast maturation and genetic features in B-cell acute lymphoblastic leukemia and predicts clinical outcome. In: Haematologica. 2011 ; Vol. 96, No. 7. pp. 980-986.
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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.",
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AU - Malumbres, Raquel

AU - Fresquet, Vicente

AU - Roman-Gomez, Jose

AU - Bobadilla, Miriam

AU - Robles, Eloy F.

AU - Altobelli, Giovanna G.

AU - Calasanz, M. José

AU - Smeland, Erlend B.

AU - Aznar, Maria Angela

AU - Agirre, Xabier

AU - Martin-Palanco, Vanesa

AU - Prosper, Felipe

AU - Lossos, Izidore

AU - Martinez-Climents, Jose A.

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N2 - 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.

AB - 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.

KW - Acute leukemia

KW - B lymphocytes

KW - Gene expression

KW - Prognostic factor

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