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ResearchIn-Press PreviewCell biologyHematologyOncology Open Access | 10.1172/JCI176818

Identification of CD84 as a potent survival factor in acute myeloid leukemia

Yinghui Zhu,1 Mariam Murtadha,2 Miaomiao Liu,1 Enrico Caserta,2 Ottavio Napolitano,2 Le Xuan Truong Nguyen,3 Huafeng Wang,4 Milad Moloudizargari,2 Lokesh Nigam,2 Theophilus Tandoh,2 Xuemei Wang,1 Alex Pozhitkov,2 Rui Su,5 Xiangjie Lin,4 Marc Denisse Estepa,2 Raju Pillai,6 Joo Song,6 James F. Sanchez,2 Yu-Hsuan Fu,3 Lianjun Zhang,3 Man Li,3 Bin Zhang,3 Ling Li,3 Ya-Huei Kuo,3 Steven Rosen,2 Guido Marcucci,3 John C. Williams,7 and Flavia Pichiorri2

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

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1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

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1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Liu, M. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Caserta, E. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

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1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Nguyen, L. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Wang, H. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

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1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

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1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

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1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Wang, X. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

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1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Su, R. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Lin, X. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Estepa, M. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Pillai, R. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Song, J. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Sanchez, J. in: JCI | PubMed | Google Scholar |

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Fu, Y. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Zhang, L. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Li, M. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Zhang, B. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Li, L. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Kuo, Y. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Rosen, S. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Marcucci, G. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

Find articles by Williams, J. in: JCI | PubMed | Google Scholar

1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Cent, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China

2Judy and Bernard Briskin Center for Multiple Myeloma Research, Department o, City of Hope, Duarte, United States of America

3Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, United States of America

4Department of Hematology, the First Affiliated Hospital, Zhejiang University School of 15 Medicine, Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China

5Department of System Biology, Beckman Research Institute, City of Hope, Duarte, United States of America

6Department of Pathology, City of Hope National Medical Center, Duarte, United States of America

7Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, United States of America

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Published April 8, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI176818.
Copyright © 2025, Zhu et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published April 8, 2025 - Version history
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Abstract

Acute myeloid leukemia (AML) is an aggressive and often deadly malignancy associated with proliferative immature myeloid blasts. Here, we identified CD84 as a critical survival regulator in AML. High levels of CD84 expression provided a survival advantage to leukemia cells, whereas CD84 downregulation disrupted their proliferation, clonogenicity and engraftment capabilities in both human cell lines and patient derived xenograft cells. Critically, loss of CD84 also markedly blocked leukemia engraftment and clonogenicity in MLL-AF9 and inv(16) AML mouse models, highlighting its pivotal role as survival factor across species. Mechanistically, CD84 regulated leukemia cells’ energy metabolism and mitochondrial dynamics. Depletion of CD84 altered mitochondrial ultra-structure and function of leukemia cells, and it caused down-modulation of both oxidative phosphorylation and fatty acid oxidation pathways. CD84 knockdown induced a block of Akt phosphorylation and down-modulation of nuclear factor erythroid 2-related factor 2 (NRF2), impairing AML antioxidant defense. Conversely, CD84 over-expression stabilized NRF2 and promoted its transcriptional activation, thereby supporting redox homeostasis and mitochondrial function in AML. Collectively, our findings indicated that AML cells depend on CD84 to support antioxidant pro-survival pathways, highlighting a therapeutic vulnerability of leukemia cells.

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