Negative regulatory elements are present in the human LMO2 oncogene and may contribute to its expression in leukemia.
Ectopic expression of LMO2 occurs in approximately 45% of T-lineage acute lymphoblastic leukemias (T-ALL), sometimes in association with chromosomal translocations. Recently, a lymphoproliferative disorder developed in two participants in a gene therapy trial due to LMO2 activation via integration of the retroviral vector. To investigate these regulatory disruptions, we analyzed the promoter region and identified a tissue-specific repressor. The fragment containing this element could also produce tissue-specific suppression of transcription from the SV40 promoter. This suppression involves histone acetylation which can be relieved with Trichostatin A (TSA). The negative element is in a region consistently removed from LMO2 in the known chromosomal translocations.
Hammond
Suzan M
SM
Department of Pediatrics, Division of Hematology/Oncology, Cincinnati, Children's Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA.
Crable
Scott C
SC
Anderson
Kathleen P
KP
D048868:Adaptor Proteins, Signal Transducing; D001483:Base Sequence; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D006655:Histone Deacetylases / Q000502:physiology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D019169:Jurkat Cells; D020014:K562 Cells; D060588:LIM Domain Proteins; D007938:Leukemia / Q000235:genetics*; D008667:Metalloproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011518:Proto-Oncogene Proteins; D011519:Proto-Oncogenes; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D006877:Hydroxamic Acids; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins; C012589:trichostatin A; D006655:Histone Deacetylases