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.

LMO2 expression reflects the different stages of blast maturation and genetic features in B-cell acute lymphoblastic leukemia and predicts clinical outcome / Malumbres, R; Fresquet, V; Roman Gomez, J; Bobadilla, M; Robles, Ef; Altobelli, GIOVANNA GIUSEPPINA; Calasanz, Mj; Smeland, Eb; Aznar, Ma; Agirre, X; Martin Palanco, V; Prosper, F; Lossos, Is; Martinez Climent, Ja. - In: HAEMATOLOGICA. - ISSN 0390-6078. - 96:(2011). [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.

ALTOBELLI, GIOVANNA GIUSEPPINA;
2011

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.
2011
LMO2 expression reflects the different stages of blast maturation and genetic features in B-cell acute lymphoblastic leukemia and predicts clinical outcome / Malumbres, R; Fresquet, V; Roman Gomez, J; Bobadilla, M; Robles, Ef; Altobelli, GIOVANNA GIUSEPPINA; Calasanz, Mj; Smeland, Eb; Aznar, Ma; Agirre, X; Martin Palanco, V; Prosper, F; Lossos, Is; Martinez Climent, Ja. - In: HAEMATOLOGICA. - ISSN 0390-6078. - 96:(2011). [10.3324/haematol.2011.040568]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/575478
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