title: Lmo2 induces hematopoietic stem cell-like features in T-cell progenitor cells prior to leukemia.
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.
authors: Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6307, USA.
authors: Susan M
authors: SM
authors: Cleveland
authors: Stephen
authors: S
authors: Smith
authors: Rati
authors: R
authors: Tripathi
authors: Elizabeth M
authors: EM
authors: Mathias
authors: Charnise
authors: C
authors: Goodings
authors: Natalina
authors: N
authors: Elliott
authors: Dunfa
authors: D
authors: Peng
authors: Wael
authors: W
authors: El-Rifai
authors: Dajun
authors: D
authors: Yi
authors: Xi
authors: X
authors: Chen
authors: Liqi
authors: L
authors: Li
authors: Charles
authors: C
authors: Mullighan
authors: James R
authors: JR
authors: Downing
authors: Paul
authors: P
authors: Love
authors: Utpal P
authors: UP
authors: Davé
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D060588:LIM Domain Proteins / Q000096:biosynthesis* / Q000235:genetics; D015458:Leukemia, T-Cell / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; C513188:Lmo2 protein, mouse
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