A Legacy of Excellence: Ken H. Young’s Continuing Contributions to Hematopathology and Blood Cancer Study

Ken H. Young, MD, PhD, professor of pathology and director of Duke's Division of Hematopathology, began his journey into hematopathology with a fascination for understanding diseases at the cellular and molecular levels. "The complex nature of the disease and its value to improve clinical management in patients is what attracted me to pathology," he explained.

Young spent his graduate career in pathology with Björn Dahlbäck, MD, who introduced him to hematology. Dahlbäck was a Swedish physician and member of the Royal Swedish Academy of Sciences. He was known for the discovery of thrombotic diseases and Factor V Leiden - a gene mutation that results in thrombophilia, which is an increased tendency to form abnormal blood clots that can block blood vessels. Young chose hematopathology as his specialty, working as a fellow with John C. Chan, MD, and Dennis D. Weisenburger, MD, at the University of Nebraska Medical Center, known for the discovery of mantle cell lymphoma and the inauguration of the Lymphoma/Leukemia Molecular Profiling Project (LLMPP).

“The significant success of LLMPP lays the foundation for the molecular classification of both B-cell and T-cell lymphoma in the world,” he said, appreciating the guidance from his mentors.

Young's work with the LLMPP and his fellowship training at the Howard Hughes Medical Institute, which allowed him to develop clinical and pathologic research on blood cancer, are standouts for him. To unite pathologists with similar academic interests and foster a better understanding of the molecular mechanisms of lymphoma and other blood cancers, he initiated a Multicenter Lymphoma Consortium. This program, composed of major hematology centers in the United States and Europe, has been highly productive, leading to 92 publications in high-impact medical journals, including 38 invited review articles. "The consortium program is composed of major hematology centers in the US and Europe, and collaboration has been very productive with combined efforts," Young noted.

Young joined Duke in 2019, where his research significantly impacts the field of lymphoma, particularly in diffuse large B-cell lymphoma (DLBCL), the most common and aggressive type of lymphoma. His work includes the development of the Visco-Young Algorithm for Practical DLBCL Classification, the impact of TP53 mutation in DLBCL in the rituximab immunotherapy era, and studies on MYC/BCL2 double expressors in DLBCL. These double expressors are associated with poor prognosis when treated with standard immunochemotherapy regimens.

"We have succeeded in the study of various therapeutic and prognostic biomarkers with important impact in the lymphoma field," he explained. His pioneering studies contribute to modifications in the International Consensus Committee (ICC) and World Health Organization (WHO) classification of high-grade B-cell lymphoma with double hit and double expression. This work helps in providing more accurate risk stratification and better treatment plans for patients, improving their outcomes and quality of life.

In the past three years, he has focused on tumor-infiltrating normal B cells in DLBCL, inspiring the development of novel immunotherapeutic strategies for patients who have a disease that doesn’t respond to an adequate course of standard treatment. His research refines the genetic signature in subsets of DLBCL based on immune biomarker expression and tumor microenvironment (TME) repertoire. Understanding TME’s composition is crucial for developing cancer therapies. Collaborative efforts within his consortium also have led and continue to lead to novel discoveries in rare blood cancers, such as primary brain and testicular lymphoma, which promise significant future clinical applications and novel drug development.

These advancements mean that patients with these rare conditions can hope for better diagnostic tools and more effective treatments. Young's Multicenter Lymphoma Consortium exemplifies the power of collaborative research in addressing clinical and pathologic questions. By combining the expertise of pathologists and hematologists from different centers worldwide, the consortium enhances academic pursuits and empowers medical contributions to improve diagnosis, treatment, and patient management.

"The clinical and pathologic collaborations among the pathologists and hematologists with similar academic interest and passion will enhance the common academic interest," Young emphasized. "This collaborative effort not only advances research but also fosters lifelong professional friendships and education among its members, ultimately improving patient care through shared knowledge and resources."

In January 2024, he collaborated with colleagues at various institutions to identify mutational cancer drivers and microenvironment factors for the progression of myeloma and lymphoma and to generate innovative and effective agents for cancer prevention and treatment. Their work resulted in the National Institutes of Health (NIH)/National Cancer Institute (NCI) awarding them a CAP-MGUS U54 Center Award. The award, totaling $4.65 million, is being disbursed over four years to the institutions who will share the funds. This funding reflects the strength of the Pathology Department and its robust collaboration with other institutions, which places it at the forefront of blood cancer pathologic and translational research. Based on progresses made in tumor microenvironmental immune cell profiling (2024 Clinical Cancer Research), novel immunotherapeutic strategy has been developed and led to new NIH/NCI R01 funding in September 2024.

He continues to drive forward clinical practice in hematopathology and pathology research in blood cancers. His leadership in the Department of Pathology is instrumental in fostering an environment of academic excellence and innovative research. In June 2023, he assumed another leadership role when he was named as the new Research Quality Leader of the Pathology Research Quality Management Program (RQMP) and Vice Chair in the Department. In this role he is responsible for innovating and implementing best practices in quality research, as well as with scientific integrity and accountability across Duke University. Outside of his professional life, Young enjoys hiking, badminton, basketball, cooking, and music, which provide a balance to his dedicated career in pathology.

Young envisions that large-scale clinical and pathologic studies will continue to support future research strategies and

treatment algorithms. These efforts elucidate disease mechanisms, discover novel therapeutic targets, and identify prognostic biomarkers for follow-up evaluation and residual disease monitoring. Importantly, this research provides valuable resources for training and educating the next generation of physicians and pathologists.

"It’s important to train and educate our next generation of young physicians and pathologists, supporting them to be successful in their future careers," he explained. This dedication ensures that future patients will receive care from highly trained professionals who are well-versed in the latest advancements in pathology.

Young finds his daily work highly rewarding, particularly in mentoring and supporting fellows, residents, and trainees in their careers. He takes pride in seeing successful young physicians and pathologists emerge from Duke University Medical Center, the Department of Pathology, and the hematopathology program. "We love to see more successful young physicians and pathologists coming from our Duke Medical Center, Pathology Department, and our Hematopathology Division, because they represent our future in the medical field," he shared.

Young's trainees speak highly of his mentorship and collaborative spirit. Now in the private sector, one of Young’s former mentees, Catherine Alexander, MD, shared, "Dr. Young has served as a role model to me throughout my hematopathology fellowship training. Not only is he prolific in terms of his research and clinical accomplishments, but he also creates a very positive working environment. He has an infectiously enthusiastic attitude and consistently advocates for the success and well-being of his trainees."

Zijun Yidan Xu-Monette, PhD, assistant professor in Duke Pathology, noted, "Dr. Young’s mentorship totally changed my career, since I had not worked on clinical aspects before the postdoctoral fellowship under his mentorship. During the postdoc job interview almost fifteen years ago, Dr. Young made me realize that using my knowledge and skills in clinical researches will be meaningful and can make significant contributions to the patients."

Beyond his dedication to mentorship, Young's long-term goals include continuing to advance the field of hematopathology through innovative research and collaboration. He aims to further develop the Multicenter Lymphoma Consortium and explore new therapeutic targets for blood cancers. Additionally, he is committed to mentoring the next generation of pathologists, ensuring they are equipped with the knowledge and skills to push the boundaries of medical science for the future.