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Monoallelic or biallelic LMO2 expression in relation to the LMO2 rearrangement status in pediatric T-cell acute lymphoblastic leukemia

Leukemia volume 22, pages 1434–1437 (2008)Cite this article

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes in which multiple genetic defects cooperate during pathogenesis resulting in uncontrolled cell growth. For T-ALL, a large variety of genetic rearrangements have been identified, including chromosomal translocations, deletions, amplifications, duplications and mutations. Translocations predominantly involve aberrant rearrangements of the T-cell receptor (TCR) loci during T-cell development through illegitimate V(D)J recombination. These recombination errors ultimately result in the activation of oncogenes.1

One such important oncogene is LMO2. In the t(11;14)(p13;q11) and t(7;11)(q35;p13) translocations, the LMO2 gene is brought in close proximity of the TCRα/δ or TCRβ enhancers possibly boosting LMO2 expression.1 Hammond et al.2 demonstrated that deletion of a negative regulatory element (NRE) located just upstream the LMO2 locus also activates the LMO2 gene. This alternative mechanism for LMO2 activation also occurs in human cancer as we identified the recurrent interstitial deletion, del(11)(p12p13), in pediatric T-ALL in which loss of the NRE region is associated with LMO2 activation.3 It was recently proposed that for most LMO2 translocations, LMO2 activation is presumably caused by the loss of the NRE region during the translocation event rather than the juxtaposition of LMO2 in the vicinity of the TCR enhancers.4

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Authors and Affiliations

  1. Department of Pediatric Oncology/Hematology, ErasmusMC-Sophia Children's Hospital, Rotterdam, The Netherlands

    P Van Vlierberghe, J Buijs-Gladdines, R Pieters & J P P Meijerink

  2. Department of Clinical Genetics, ErasmusMC, Rotterdam, The Netherlands

    H B Beverloo

  3. Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands

    E R van Wering

  4. German Co-Operative Study Group for Childhood Acute Lymphoblastic Leukemia (COALL), Hamburg, Germany

    M Horstmann

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  1. P Van Vlierberghe
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  2. H B Beverloo
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  4. E R van Wering
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  7. J P P Meijerink
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Correspondence to J P P Meijerink.

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Van Vlierberghe, P., Beverloo, H., Buijs-Gladdines, J. et al. Monoallelic or biallelic LMO2 expression in relation to the LMO2 rearrangement status in pediatric T-cell acute lymphoblastic leukemia. Leukemia 22, 1434–1437 (2008). https://doi.org/10.1038/sj.leu.2405063

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