Nature Communications (Jul 2021)
The role of the PZP domain of AF10 in acute leukemia driven by AF10 translocations
- Brianna J. Klein,
- Anagha Deshpande,
- Khan L. Cox,
- Fan Xuan,
- Mohamad Zandian,
- Karina Barbosa,
- Sujita Khanal,
- Qiong Tong,
- Yi Zhang,
- Pan Zhang,
- Amit Sinha,
- Stefan K. Bohlander,
- Xiaobing Shi,
- Hong Wen,
- Michael G. Poirier,
- Aniruddha J. Deshpande,
- Tatiana G. Kutateladze
Affiliations
- Brianna J. Klein
- Department of Pharmacology, University of Colorado School of Medicine
- Anagha Deshpande
- Tumor Initiation and Maintenance Program, National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute
- Khan L. Cox
- Department of Physics, Ohio State University
- Fan Xuan
- Center for Epigenetics, Van Andel Research Institute
- Mohamad Zandian
- Department of Pharmacology, University of Colorado School of Medicine
- Karina Barbosa
- Tumor Initiation and Maintenance Program, National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute
- Sujita Khanal
- Tumor Initiation and Maintenance Program, National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute
- Qiong Tong
- Department of Pharmacology, University of Colorado School of Medicine
- Yi Zhang
- Department of Pharmacology, University of Colorado School of Medicine
- Pan Zhang
- Tumor Initiation and Maintenance Program, National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute
- Amit Sinha
- Basepair Inc
- Stefan K. Bohlander
- Leukaemia and Blood Cancer Research Unit, Department of Molecular Medicine and Pathology, University of Auckland
- Xiaobing Shi
- Center for Epigenetics, Van Andel Research Institute
- Hong Wen
- Center for Epigenetics, Van Andel Research Institute
- Michael G. Poirier
- Department of Physics, Ohio State University
- Aniruddha J. Deshpande
- Tumor Initiation and Maintenance Program, National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute
- Tatiana G. Kutateladze
- Department of Pharmacology, University of Colorado School of Medicine
- DOI
- https://doi.org/10.1038/s41467-021-24418-9
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 15
Abstract
Chromosomal translocations involving the AF10 gene, especially with CALM, are associated with aggressive leukemias. Here the authors show that the PZP domain of AF10, a histone reader, is always excluded/impaired in AF10 fusions, whereas incorporation of this domain downregulates Hoxa genes and blocks leukemogenesis.