Sox4 Is a Key Oncogenic Target in C/EBP alpha Mutant Acute Myeloid Leukemia

H Zhang; M Alberich-Jorda; G Amabile; H Yang; PB Staber; A DiRuscio; RS Welner; A Ebralidze; JY Zhang; E (Elena) Levantini; V Lefebvre; Peter Valk; Ruud Delwel; M Hoogenkamp; C Nerlov; J Cammenga; B Saez; DT Scadden; C Bonifer; M Ye; DG Tenen

doi:10.1016/j.ccr.2013.09.018

Sox4 Is a Key Oncogenic Target in C/EBP alpha Mutant Acute Myeloid Leukemia

H Zhang, M Alberich-Jorda, G Amabile, H Yang, PB Staber, A DiRuscio, RS Welner, A Ebralidze, JY Zhang, E (Elena) Levantini, V Lefebvre, Peter Valk, Ruud Delwel, M Hoogenkamp, C Nerlov, J Cammenga, B Saez, DT Scadden, C Bonifer, M YeDG Tenen

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Mutation or epigenetic silencing of the transcription factor C/EBP alpha is observed in similar to 10% of patients with acute myeloid leukemia (AML). In both cases, a common global gene expression profile is observed, but downstream targets relevant for leukemogenesis are not known. Here, we identify Sox4 as a direct target of C/EBP alpha whereby its expression is inversely correlated with C/EBP alpha activity. Downregulation of Sox4 abrogated increased self-renewal of leukemic cells and restored their differentiation. Gene expression profiles of leukemia-initiating cells (LICs) from both Sox4 overexpression and murine C/EBP alpha mutant AML models clustered together but differed from other types of AML. Our data demonstrate that Sox4 overexpression resulting from C/EBP alpha inactivation contributes to the development of leukemia with a distinct LIC phenotype.

Original language	Undefined/Unknown
Pages (from-to)	575-588
Number of pages	14
Journal	Cancer Cell
Volume	24
Issue number	5
DOIs	https://doi.org/10.1016/j.ccr.2013.09.018
Publication status	Published - 2013

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10.1016/j.ccr.2013.09.018

http://hdl.handle.net/1765/54351

Cite this

Zhang, H., Alberich-Jorda, M., Amabile, G., Yang, H., Staber, PB., DiRuscio, A., Welner, RS., Ebralidze, A., Zhang, JY., Levantini, E., Lefebvre, V., Valk, P., Delwel, R., Hoogenkamp, M., Nerlov, C., Cammenga, J., Saez, B., Scadden, DT., Bonifer, C., ... Tenen, DG. (2013). Sox4 Is a Key Oncogenic Target in C/EBP alpha Mutant Acute Myeloid Leukemia. Cancer Cell, 24(5), 575-588. https://doi.org/10.1016/j.ccr.2013.09.018

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title = "Sox4 Is a Key Oncogenic Target in C/EBP alpha Mutant Acute Myeloid Leukemia",

abstract = "Mutation or epigenetic silencing of the transcription factor C/EBP alpha is observed in similar to 10% of patients with acute myeloid leukemia (AML). In both cases, a common global gene expression profile is observed, but downstream targets relevant for leukemogenesis are not known. Here, we identify Sox4 as a direct target of C/EBP alpha whereby its expression is inversely correlated with C/EBP alpha activity. Downregulation of Sox4 abrogated increased self-renewal of leukemic cells and restored their differentiation. Gene expression profiles of leukemia-initiating cells (LICs) from both Sox4 overexpression and murine C/EBP alpha mutant AML models clustered together but differed from other types of AML. Our data demonstrate that Sox4 overexpression resulting from C/EBP alpha inactivation contributes to the development of leukemia with a distinct LIC phenotype.",

author = "H Zhang and M Alberich-Jorda and G Amabile and H Yang and PB Staber and A DiRuscio and RS Welner and A Ebralidze and JY Zhang and Levantini, {E (Elena)} and V Lefebvre and Peter Valk and Ruud Delwel and M Hoogenkamp and C Nerlov and J Cammenga and B Saez and DT Scadden and C Bonifer and M Ye and DG Tenen",

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doi = "10.1016/j.ccr.2013.09.018",

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Zhang, H, Alberich-Jorda, M, Amabile, G, Yang, H, Staber, PB, DiRuscio, A, Welner, RS, Ebralidze, A, Zhang, JY, Levantini, E, Lefebvre, V, Valk, P , Delwel, R, Hoogenkamp, M, Nerlov, C, Cammenga, J, Saez, B, Scadden, DT, Bonifer, C, Ye, M & Tenen, DG 2013, 'Sox4 Is a Key Oncogenic Target in C/EBP alpha Mutant Acute Myeloid Leukemia', Cancer Cell, vol. 24, no. 5, pp. 575-588. https://doi.org/10.1016/j.ccr.2013.09.018

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T1 - Sox4 Is a Key Oncogenic Target in C/EBP alpha Mutant Acute Myeloid Leukemia

AU - Zhang, H

AU - Alberich-Jorda, M

AU - Amabile, G

AU - Yang, H

AU - Staber, PB

AU - DiRuscio, A

AU - Welner, RS

AU - Ebralidze, A

AU - Zhang, JY

AU - Levantini, E (Elena)

AU - Lefebvre, V

AU - Valk, Peter

AU - Delwel, Ruud

AU - Hoogenkamp, M

AU - Nerlov, C

AU - Cammenga, J

AU - Saez, B

AU - Scadden, DT

AU - Bonifer, C

AU - Ye, M

AU - Tenen, DG

PY - 2013

Y1 - 2013

N2 - Mutation or epigenetic silencing of the transcription factor C/EBP alpha is observed in similar to 10% of patients with acute myeloid leukemia (AML). In both cases, a common global gene expression profile is observed, but downstream targets relevant for leukemogenesis are not known. Here, we identify Sox4 as a direct target of C/EBP alpha whereby its expression is inversely correlated with C/EBP alpha activity. Downregulation of Sox4 abrogated increased self-renewal of leukemic cells and restored their differentiation. Gene expression profiles of leukemia-initiating cells (LICs) from both Sox4 overexpression and murine C/EBP alpha mutant AML models clustered together but differed from other types of AML. Our data demonstrate that Sox4 overexpression resulting from C/EBP alpha inactivation contributes to the development of leukemia with a distinct LIC phenotype.

AB - Mutation or epigenetic silencing of the transcription factor C/EBP alpha is observed in similar to 10% of patients with acute myeloid leukemia (AML). In both cases, a common global gene expression profile is observed, but downstream targets relevant for leukemogenesis are not known. Here, we identify Sox4 as a direct target of C/EBP alpha whereby its expression is inversely correlated with C/EBP alpha activity. Downregulation of Sox4 abrogated increased self-renewal of leukemic cells and restored their differentiation. Gene expression profiles of leukemia-initiating cells (LICs) from both Sox4 overexpression and murine C/EBP alpha mutant AML models clustered together but differed from other types of AML. Our data demonstrate that Sox4 overexpression resulting from C/EBP alpha inactivation contributes to the development of leukemia with a distinct LIC phenotype.

U2 - 10.1016/j.ccr.2013.09.018

DO - 10.1016/j.ccr.2013.09.018

M3 - Article

VL - 24

SP - 575

EP - 588

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 5

ER -