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DNA methylation in circulating leukocytes is a novel biomarker in multiple myeloma

Bone Marrow Transplantation volume 58, pages 334–336 (2023)Cite this article

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We recently reported long-term trajectories of quality of life (QOL) recovery after standard-of-care high-dose melphalan conditioning, autologous hematopoietic cell transplantation (AHCT), and post-transplant lenalidomide maintenance in multiple myeloma (MM) [1]. We found that by 1 year post transplantation, MM survivors who achieved disease control recovered Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) scores, even exceeding population norms. Nonetheless, many patients continued to experience moderate to severe levels of symptom burden beyond 1 year [1].

While patient-reported outcomes (PROs) are established clinical outcomes, few studies have explored relations with known biomarkers in disease processes. Conducting such research can aid in the mechanistic understanding of symptom burden and the potential for biomarker-focused therapeutic interventions to improve QOL. A large body of evidence exists on the utility of circulating leukocyte DNA methylation as a biomarker of cancer [2, 3], hematopoietic cell transplantation [4], and in the natural history of mature B-cell tumors [5]. The impact of aberrant DNA methylation on MM development, progression, and outcome is also well established [6]. Thus, we conducted an ancillary follow-up study aimed at complementing PROs with DNA methylation measurement.

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Fig. 1: PBMC DNA methylation in patients with myeloma from the BMT CTN 0702 (STaMINA) phase 3 trial.

Data availability

The clinical data that support the findings of this study are publicly available at BioLINCC: Blood and Marrow Transplant Clinical Trials Network (BMT CTN) A Trial of Single Autologous Transplant With or Without Consolidation Therapy Versus Tandem Autologous Transplant With Lenalidomide Maintenance for Patients With Multiple Myeloma (0702) (nih.gov). DNA methylation data will be shared upon reasonable request with the corresponding author.

References

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Acknowledgements

This ancillary study was funded by a Froedtert & MCW Cancer Center grant (project 3379013). AD is supported by K23 HL141445. The BMT CTN 0702 was supported by Grant No. U10HL069294 to the Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung, and Blood Institute and the National Cancer Institute; by Celgene Corporation and Millennium (Takeda) Pharmaceuticals; and by The Alliance for Clinical Trials in Oncology, the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group, and SWOG. The content of this article is solely the responsibility of the authors and does not represent the official views of the funding parties.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

    Anita D’Souza, Hannah Uttley, Jing Dong, Marcelo C. Pasquini & Siegfried Janz

  2. Division of Biostatistics, Insitute of Health and Equity, Medical College of Wisconsin, Milwaukee, WI, USA

    Ruta Brazauskas & Bi Qing Teng

  3. MCW Medical School, Milwaukee, WI, USA

    Grant Yun

  4. Center for Immunology, Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI, USA

    Michael B. Dwinell

  5. Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Sergio Giralt & Heather Landau

  6. Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Edward Stadtmauer

  7. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Cancer Center, Duarte, CA, USA

    Amrita Krishnan

Authors
  1. Anita D’Souza
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  13. Siegfried Janz
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Contributions

AD designed the study, obtained funding, reviewed the analysis, and wrote the manuscript. RB designed and conducted the biostatistical analysis, and edited the manuscript. BQT conducted biostatistical analysis. GY, HU and SJ conducted the DNA methylation assays, reviewed the analysis, and edited the manuscript. JD and MBD reviewed the analysis and edited the manuscript. MCP (Protocol Officer, BMT CTN 0702), SG, HL, ES (Protocol Co-Chair, BMT CTN 0702), and AK (Protocol Co-Chair, BMT CTN 0702) led the BMT CTN 0702 study and/or were from the top 3 centers that provided data contributing to this study, reviewed the current analysis, and edited the manuscript. All authors approved the final manuscript draft.

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Correspondence to Anita D’Souza.

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D’Souza, A., Brazauskas, R., Teng, B.Q. et al. DNA methylation in circulating leukocytes is a novel biomarker in multiple myeloma. Bone Marrow Transplant 58, 334–336 (2023). https://doi.org/10.1038/s41409-022-01887-0

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