Biallelic transcriptional activation of oncogenic transcription factors in T-cell acute lymphoblastic leukemia
2003; Elsevier BV; Volume: 103; Issue: 5 Linguagem: Inglês
10.1182/blood-2003-07-2577
ISSN1528-0020
AutoresAdolfo A. Ferrando, Sabine Herblot, Teresa Palomero, Thomas Hansen, Trang Hoang, Edward A. Fox, A. Thomas Look,
Tópico(s)Acute Myeloid Leukemia Research
ResumoAberrant expression of transcription factor oncogenes such as HOX11, HOX11L2, TAL1/SCL, LYL1, LMO1, and LMO2 can be detected in lymphoblasts from up to 80% of patients with acute T-cell lymphoblastic leukemia (T-ALL). Transcriptional activation of these oncogenes in leukemic cells typically results from chromosomal rearrangements that place them next to highly active cis-acting transcriptional regulatory elements. However, biallelic activation of TAL1 in some T-ALL cases has been previously proposed. We have used allele-specific mRNA analysis to show that trans-acting mechanisms leading to biallelic overexpression of TAL1 are involved in 10 (42%) of 24 TAL1+ informative T-ALL cases, 2 (17%) of 12 HOX11+ informative cases, and 7 (64%) of 11 LMO2+ informative cases. We propose that aberrant expression of oncogenic transcription factors in a significant fraction of T-ALLs may result from loss of the upstream transcriptional mechanisms that normally down-regulate the expression of these oncogenes during T-cell development.
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