PU.1 is essential for MLL leukemia partially via crosstalk with the MEIS/HOX pathway

J. Zhou, J. Wu, B. Li, D. Liu, J. Yu, X. Yan, S. Zheng, J. Wang, L. Zhang, L. Zhang, F. He, Q. Li, A. Chen, Y. Zhang, X. Zhao, Y. Guan, X. Zhao, J. Yan, J. Ni, M. A. NobregaB. Löwenberg, R. Delwel, P. J.M. Valk, A. Kumar, L. Xie, D. G. Tenen, G. Huang, Q. F. Wang

Producción científica: Articlerevisión exhaustiva

38 Citas (Scopus)


Mixed lineage leukemia (MLL) fusion proteins directly activate the expression of key downstream genes such as MEIS1, HOXA9 to drive an aggressive form of human leukemia. However, it is still poorly understood what additional transcriptional regulators, independent of the MLL fusion pathway, contribute to the development of MLL leukemia. Here we show that the transcription factor PU.1 is essential for MLL leukemia and is required for the growth of MLL leukemic cells via the promotion of cell-cycle progression and inhibition of apoptosis. Importantly, PU.1 expression is not under the control of MLL fusion proteins. We further identified a PU.1-governed 15-gene signature, which contains key regulators in the MEIS-HOX program (MEIS1, PBX3, FLT3, and c-KIT). PU.1 directly binds to the genomic loci of its target genes in vivo, and is required to maintain active expression of those genes in both normal hematopoietic stem and progenitor cells and in MLL leukemia. Finally, the clinical significance of the identified PU.1 signature was indicated by its ability to predict survival in acute myelogenous leukemia patients. Together, our findings demonstrate that PU.1 contributes to the development of MLL leukemia, partially via crosstalk with the MEIS/HOX pathway.

Idioma originalEnglish (US)
Páginas (desde-hasta)1436-1448
Número de páginas13
EstadoPublished - jul 2014
Publicado de forma externa

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


Profundice en los temas de investigación de 'PU.1 is essential for MLL leukemia partially via crosstalk with the MEIS/HOX pathway'. En conjunto forman una huella única.

Citar esto