Unknown

Dataset Information

0

NKX3.1 is a direct TAL1 target gene that mediates proliferation of TAL1-expressing human T cell acute lymphoblastic leukemia.


ABSTRACT: TAL1 (also known as SCL) is expressed in >40% of human T cell acute lymphoblastic leukemias (T-ALLs). TAL1 encodes a basic helix-loop-helix transcription factor that can interfere with the transcriptional activity of E2A and HEB during T cell leukemogenesis; however, the oncogenic pathways directly activated by TAL1 are not characterized. In this study, we show that, in human TAL1-expressing T-ALL cell lines, TAL1 directly activates NKX3.1, a tumor suppressor gene required for prostate stem cell maintenance. In human T-ALL cell lines, NKX3.1 gene activation is mediated by a TAL1-LMO-Ldb1 complex that is recruited by GATA-3 bound to an NKX3.1 gene promoter regulatory sequence. TAL1-induced NKX3.1 activation is associated with suppression of HP1-? (heterochromatin protein 1 ?) binding and opening of chromatin on the NKX3.1 gene promoter. NKX3.1 is necessary for T-ALL proliferation, can partially restore proliferation in TAL1 knockdown cells, and directly regulates miR-17-92. In primary human TAL1-expressing leukemic cells, the NKX3.1 gene is expressed independently of the Notch pathway, and its inactivation impairs proliferation. Finally, TAL1 or NKX3.1 knockdown abrogates the ability of human T-ALL cells to efficiently induce leukemia development in mice. These results suggest that tumor suppressor or oncogenic activity of NKX3.1 depends on tissue expression.

SUBMITTER: Kusy S 

PROVIDER: S-EPMC2947082 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

NKX3.1 is a direct TAL1 target gene that mediates proliferation of TAL1-expressing human T cell acute lymphoblastic leukemia.

Kusy Sophie S   Gerby Bastien B   Goardon Nicolas N   Gault Nathalie N   Ferri Federica F   Gérard Delphine D   Armstrong Florence F   Ballerini Paola P   Cayuela Jean-Michel JM   Baruchel André A   Pflumio Françoise F   Roméo Paul-Henri PH  

The Journal of experimental medicine 20100920 10


TAL1 (also known as SCL) is expressed in >40% of human T cell acute lymphoblastic leukemias (T-ALLs). TAL1 encodes a basic helix-loop-helix transcription factor that can interfere with the transcriptional activity of E2A and HEB during T cell leukemogenesis; however, the oncogenic pathways directly activated by TAL1 are not characterized. In this study, we show that, in human TAL1-expressing T-ALL cell lines, TAL1 directly activates NKX3.1, a tumor suppressor gene required for prostate stem cell  ...[more]

Similar Datasets

| S-EPMC4884991 | biostudies-literature
| S-EPMC1895859 | biostudies-literature
| S-EPMC4782046 | biostudies-literature
| S-EPMC8197659 | biostudies-literature
| S-EPMC3422504 | biostudies-literature
| S-EPMC1536060 | biostudies-literature
| S-EPMC4634719 | biostudies-other
| S-EPMC6127084 | biostudies-other
| S-EPMC7848433 | biostudies-literature
| S-EPMC3727321 | biostudies-literature