
LIM domain only-2 (LMO2) overexpression in T cells induces leukemia but the molecular mechanism remains to be elucidated. In hematopoietic stem and progenitor cells, Lmo2 is part of a protein complex comprised of class II basic helix loop helix proteins, Tal1and Lyl1. The latter transcription factors heterodimerize with E2A proteins like E47 and Heb to bind E boxes. LMO2 and TAL1 or LYL1 cooperate to induce T-ALL in mouse models, and are concordantly expressed in human T-ALL. Furthermore, LMO2 cooperates with the loss of E2A suggesting that LMO2 functions by creating a deficiency of E2A. In this study, we tested this hypothesis in Lmo2-induced T-ALL cell lines. We transduced these lines with an E47/estrogen receptor fusion construct that could be forced to homodimerize with 4-hydroxytamoxifen. We discovered that forced homodimerization induced growth arrest in 2 of the 4 lines tested. The lines sensitive to E47 homodimerization accumulated in G1 and had reduced S phase entry. We analyzed the transcriptome of a resistant and a sensitive line to discern the E47 targets responsible for the cellular effects. Our results suggest that E47 has diverse effects in T-ALL but that functional deficiency of E47 is not a universal feature of Lmo2-induced T-ALL.
Leukemia, T-Cell, Cell Cycle Checkpoints, LIM Domain Proteins, Response Elements, Transcription Factor 3, Cell Transformation, Neoplastic, Cell Line, Tumor, Proto-Oncogene Proteins, Basic Helix-Loop-Helix Transcription Factors, Humans, Protein Multimerization, Adaptor Proteins, Signal Transducing
Leukemia, T-Cell, Cell Cycle Checkpoints, LIM Domain Proteins, Response Elements, Transcription Factor 3, Cell Transformation, Neoplastic, Cell Line, Tumor, Proto-Oncogene Proteins, Basic Helix-Loop-Helix Transcription Factors, Humans, Protein Multimerization, Adaptor Proteins, Signal Transducing
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