Lmo2 induces hematopoietic stem cell-like features in T-cell progenitor cells prior to leukemia

Susan M. Cleveland, Stephen Smith, Rati Tripathi, Elizabeth M. Mathias, Charnise Goodings, Natalina Elliott, Dunfa Peng, Wael El-Rifai, Dajun Yi, Xi Chen, Liqi Li, Charles Mullighan, James R. Downing, Paul Love, Utpal P. Davé

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

LIM domain only 2 (Lmo2) is frequently deregulated in sporadic and gene therapy-induced acute T-cell lymphoblastic leukemia (T-ALL) where its overexpression is an important initiating mutational event. In transgenic and retroviral mouse models, Lmo2 expression can be enforced in multiple hematopoietic lineages but leukemia only arises from T cells. These data suggest that Lmo2 confers clonal growth advantage in T-cell progenitors. We analyzed proliferation, differentiation, and cell death in CD2-Lmo2 transgenic thymic progenitor cells to understand the cellular effects of enforced Lmo2 expression. Most impressively, Lmo2 transgenic T-cell progenitor cells were blocked in differentiation, quiescent, and immortalized in vitro on OP9-DL1 stromal cells. These cellular effects were concordant with a transcriptional signature in Lmo2 transgenic T-cell progenitor cells that is also present in hematopoietic stem cells (HSCs) and early T-cell precursor ALL. These results are significant in light of the crucial role of Lmo2 in the maintenance of the HSC. The cellular effects and transcriptional effects have implications for LMO2-dependent leukemogenesis and the treatment of LMO2-induced T-ALL.

Original languageEnglish (US)
Pages (from-to)882-894
Number of pages13
JournalSTEM CELLS
Volume31
Issue number5
DOIs
StatePublished - May 2013

Keywords

  • Hematopoiesis
  • Leukemia
  • Stem cells
  • T cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Cleveland, S. M., Smith, S., Tripathi, R., Mathias, E. M., Goodings, C., Elliott, N., Peng, D., El-Rifai, W., Yi, D., Chen, X., Li, L., Mullighan, C., Downing, J. R., Love, P., & Davé, U. P. (2013). Lmo2 induces hematopoietic stem cell-like features in T-cell progenitor cells prior to leukemia. STEM CELLS, 31(5), 882-894. https://doi.org/10.1002/stem.1345