J Cancer Prev.
2022 Jun;27(2):129-138. 10.15430/JCP.2022.27.2.129.
A Pilot Clinical Study to Investigate the Hypomethylating Properties of Freeze-dried Black Raspberries in Patients with Myelodysplastic Syndrome or Myeloproliferative Neoplasm
- Dong A
1 - Pan X2
- Lin CW3
- Huang YW4
- Krause H1
- Pan P1
- Baim A1
- Thomas MJ5
- Chen X1
- Yu J6
- Michaelis L1
- Liu P7
- Wang LS1
- Atallah E1
- Affiliations
-
- 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, Medical College of Wisconsin, Milwaukee, WI, USA
- 4Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, USA
- 5Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA
- 6Department of Hematology and Hematopoietic Cell Transplantation, Comprehensive Cancer Center, City of Hope National Medical Center, Duarte, CA, USA
- 7Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
- KMID: 2531047
- DOI: http://doi.org/10.15430/JCP.2022.27.2.129
Abstract
- 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.
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