Lmo2 Induces Hematopoietic Stem Cell‐Like Features in T‐Cell Progenitor Cells Prior to Leukemia123. (24th April 2013)

• Record Type: Journal Article
• Authors: Cleveland, Susan M.; Smith, Stephen; Tripathi, Rati; Mathias, Elizabeth M.; Goodings, Charnise; Elliott, Natalina; Peng, Dunfa; El‐Rifai, Wael; Yi, Dajun; Chen, Xi; Li, Liqi; Mullighan, Charles; Downing, James R.; Love, Paul; Davé, Utpal P.
• Is Part Of: Stem cells. Volume 31:Number 5(2013:May)
• Page Start: 882
• Page End: 894
• Publication Date: 2013-04-24
• Subjects: Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1345
• Languages: English
• ISSNs: 1066-5099

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p> <italic>LIM domain only 2</italic> (<italic>Lmo2</italic>) 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, <italic>Lmo2</italic> expression can be enforced in multiple hematopoietic lineages but leukemia only arises from T cells. These data suggest that <italic>Lmo2</italic> confers clonal growth advantage in T‐cell progenitors. We analyzed proliferation, differentiation, and cell death in <italic>CD2‐Lmo2</italic> transgenic thymic progenitor cells to understand the cellular effects of enforced <italic>Lmo2</italic> expression. Most impressively, <italic>Lmo2</italic> 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 <italic>Lmo2</italic> 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 <italic>Lmo2</italic> in the maintenance of the HSC. The cellular effects and transcriptional effects have implications for <italic>LMO2</italic>‐dependent leukemogenesis and the treatment of <italic>LMO2</italic>‐induced T‐ALL. S<sc>TEM</sc> C<sc>ELLS</sc> 2013;31:882–894</p> </abstract>