Biallelic transcriptional activation of oncogenic transcription factors in T-cell acute lymphoblastic leukemia.
Aberrant 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.
Ferrando
Adolfo A
AA
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Herblot
Sabine
S
Palomero
Teresa
T
Hansen
Mark
M
Hoang
Trang
T
Fox
Edward A
EA
Look
A Thomas
AT
D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D051792:Basic Helix-Loop-Helix Proteins; D002469:Cell Separation; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005434:Flow Cytometry; D015321:Gene Rearrangement; D020868:Gene Silencing; D006801:Humans; D060588:LIM Domain Proteins; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008667:Metalloproteins / Q000096:biosynthesis; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C085117:LMO2 protein, human; C067143:TAL1 protein, human