Format

Send to

Choose Destination
See comment in PubMed Commons below
Haematologica. 2014 Oct;99(10):1591-8. doi: 10.3324/haematol.2014.104695. Epub 2014 Jul 4.

The Sox4/Tcf7l1 axis promotes progression of BCR-ABL-positive acute lymphoblastic leukemia.

Author information

1
Department of Laboratory Medicine and the Center for Stem Cell and Developmental Biology, The University of Texas MD Anderson Cancer Center (MDACC), Houston, TX, USA Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
2
Department of Laboratory Medicine and the Center for Stem Cell and Developmental Biology, The University of Texas MD Anderson Cancer Center (MDACC), Houston, TX, USA.
3
Department of Molecular Carcinogenesis, The University of Texas MDACC, Houston, TX, USA.
4
Department of Translational Molecular Pathology, The University of Texas MDACC, Houston, TX, USA.
5
Department of Pathology, The University of Texas MDACC, Houston, TX, USA.
6
Department of Nanomedicine, Houston Methodist Research Institute, TX, and Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY, USA.
7
Department of Hematopathology, The University of Texas MDACC, Houston, TX, USA.
8
School of Health Sciences, The University of Texas MDACC, Houston, TX, USA.
9
Department of Pediatrics, The University of Texas MDACC, Houston, TX, USA.
10
Department of Pathology, Stony Brook University Medical Center, Stony Brook, NY, USA.
11
Department of Leukemia, The University of Texas MDACC, Houston, TX, USA.
12
Department of Microbiology and Immunology, The Medical University of South Carolina, Charleston, and Department of Pathology & Laboratory Medicine, The University of Texas Houston Health Science Center, Houston, TX, USA.
13
Department of Laboratory Medicine and the Center for Stem Cell and Developmental Biology, The University of Texas MD Anderson Cancer Center (MDACC), Houston, TX, USA xsun@mdanderson.org.

Abstract

The transcription factor Sox4 plays an indispensable role in the development of early progenitor B cells from hematopoietic stem cells. However, its role in B-cell acute lymphoblastic leukemia, a malignant counterpart of normal progenitor B cells, is not fully understood. Here we show that SOX4 is highly expressed in human acute lymphoblastic leukemia cells. To systematically study the function of Sox4 in acute lymphoblastic leukemia, we established a genetically defined mouse leukemia model by transforming progenitor B cells carrying a floxed Sox4 allele and inducing deletion of the allele by the self-excising Cre recombinase. This model allowed us to work with two groups of leukemic cells that had either one copy or both copies of Sox4 deleted. We found that depletion of Sox4 in transformed cells in vitro reduced cell growth in vitro and the progression of leukemia in vivo. Moreover, depletion of Sox4 in leukemic cells in vivo prolonged the survival of the mice, suggesting that it could be a potential target in acute lymphoblastic leukemia therapy. Our microarray and bioChIP studies revealed that Tcf7l1 was the key gene directly regulated by Sox4. Knockdown of Tcf7l1 reduced cell proliferation, just as did knockout of Sox4, and ectopic expression of Tcf7l1 could reverse the effect of Sox4 knockout on cell proliferation. These data suggest that Sox4 and Tcf7l1 form a functional axis that promotes the progression of BCR-ABL-positive acute lymphoblastic leukemia.

PMID:
24997151
PMCID:
PMC4181255
DOI:
10.3324/haematol.2014.104695
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center