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Journal of Cancer Prevention

Original Article

J Cancer Prev 2022; 27(2): 129-138

Published online June 30, 2022

© Korean Society of Cancer Prevention

A Pilot Clinical Study to Investigate the Hypomethylating Properties of Freeze-dried Black Raspberries in Patients with Myelodysplastic Syndrome or Myeloproliferative Neoplasm

Athena Dong1,* , Xiaoqing Pan2,* , Chien-Wei Lin3,* , Yi-Wen Huang4,* , Hayden Krause1 , Pan Pan1 , Arielle Baim1 , Michael J Thomas5 , Xiao Chen1 , Jianhua Yu6 , Laura Michaelis1 , Pengyuan Liu7,** , Li-Shu Wang1,** , Ehab Atallah1,**

1Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA, 2Department of Mathematics, Shanghai Normal University, Shanghai, China, 3Division of Biostatistics, Medical College of Wisconsin, 4Department of Obstetrics and Gynecology, 5Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, WI, 6Department of Hematology and Hematopoietic Cell Transplantation, Comprehensive Cancer Center, City of Hope National Medical Center, Duarte, CA, 7Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA

Correspondence to :
Pengyuan Liu, E-mail:,
Li-Shu Wang, E-mail:,
Ehab Atallah, E-mail:,
*These authors contributed equally to this work as co-first authors.
**These authors contributed equally to this work as co-correspondence authors.

Received: May 20, 2022; Revised: June 9, 2022; Accepted: June 9, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are bone marrow disorders characterized by cytopenias and progression to acute myeloid leukemia. Hypomethylating agents (HMAs) are Food and Drug Administration-approved therapies for MDS and MDS/MPN patients. HMAs have improved patients’ survival and quality of life when compared with other therapies. Although HMAs are effective in MDS and MDS/MPN patients, they are associated with significant toxicities that place a large burden on patients. Our goal is to develop a safer and more effective HMA from natural products. We previously reported that black raspberries (BRBs) have hypomethylating effects in the colon, blood, spleen, and bone marrow of mice. In addition, BRBs exert hypomethylating effects in patients with colorectal cancer and familial adenomatous polyposis. In the current study, we conducted a pilot clinical trial to evaluate the hypomethylating effects of BRBs in patients with low-risk MDS or MDS/MPN. Peripheral blood mononuclear cells (PBMCs) were isolated before and after three months of BRB intervention. CD45+ cells were isolated from PBMCs for methylation analysis using a reduced-representation bisulfite sequencing assay. Each patient served as their own matched control, with their measurements assessed before intervention providing a baseline for post-intervention results. Clinically, our data showed that BRBs were well-tolerated with no side effects. When methylation data was combined, BRBs significantly affected methylation levels of 477 promoter regions. Pathway analysis suggests that BRB-induced intragenic hypomethylation drives leukocyte differentiation. A randomized, placebo-controlled clinical trial of BRB use in low-risk MDS or MDS/MPN patients is warranted.

Keywords: Rubus, Myelodysplastic syndromes, Leukocytes, mononuclear, Peripheral blood stem cells, Clinical trial


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