The Movement of Medicine: The Mindful Path of an MPN Giant

Ayalew Tefferi, MD, walks 30,000 steps per day.

“The thing is,” Tefferi, professor of medicine and consultant in the Division of Hematology, Department of Internal Medicine, at Mayo Clinic, said, “when I walk, I am meditating. I am writing my papers. I’m thinking of my projects. I am coming up with the right title. I’m coming back with the right abstract. I am coming up with the right strategy to do a clinical trial. I’m coming up with the right strategy to educate and so forth.”

Tefferi is disciplined in his practice, trekking 3 or 4 hours a day and taking all of his meetings while roaming around the Mayo Clinic campus. Movement is so critical to Tefferi’s life that, if he were not an oncologist, he said he would be a marathon runner, or even a construction worker.

“I like to do something that requires physical movement,” Tefferi said. “I need to move.” The same energy that propels him forward physically also powers his deep commitment to myeloproliferative neoplasm (MPN) research and translational science. His driving force, above all, is his commitment to his patients and ensuring the best possible care.

From passion to purpose: A career in medicine

Tefferi, who was named a 2025 Giant of Cancer Care for Community Outreach/Education, came into his specialty through the guidance of one of his mentors, Murray Silverstein, MD, of Mayo Clinic. However, Tefferi noted that his entry into the field of MPNs came about through knowing his skills and identifying the opportunity. Silverstein was a leader in the field, playing a pivotal role in defining the clinical characteristics and natural history of the disease.

“I knew where the opportunity was, because Dr Silverstein was the world-renowned expert in this field, and Mayo Clinic has a large database of these patients. I could have gone to lymphoma or myeloma— very crowded fields—but [MPNs] was not as crowded. So, there were opportunities, and I jumped into it,” Tefferi explained. “Medicine is medicine. It doesn’t really matter what you do…. It’s all about the same disease processes. The fun is the same. You just have to know where you would fit better and where you will grow.”

Tefferi has always been interested in and drawn to biology, and his decision to pursue medicine was born out of his desire to marry his interests with the ability to do good.

“You only have one life to live, and you have to live it the best way you can,” he said. “So, I thought going into medicine would accomplish both missions—my interest in biology as well as doing something that’s worthy in life.”

After attending the University of Athens Medical School and a residency at St Joseph Hospital in Chicago, Illinois, Tefferi went on to pursue a residency and fellowship in 1989 at Mayo Clinic, thanks to another early mentor, Christine Winter, MD, who was then the hematology chief at St Joseph.

“She took a liking to me, and she simply picked up the phone and called Mayo Clinic, because that’s where she was trained,” Tefferi recalled. “She told them, ‘Take Tefferi,’ and that was it.”

Tefferi also cited Robert Kyle, MD, professor of medicine at Mayo Clinic, as another role model. At 97 years old, Kyle is still working, and Tefferi often sees him on his afternoon walks through the Mayo Clinic campus.

“To me, he is the picture of a person who is selfless, whose work ethic is totally unmatched and second to none. Brilliant and always reliable and loyal,” Tefferi said. “He was a wonderful role model to be around. He is the one who pushed me into scholarly activities and publications, but most importantly, keeping your integrity.”

Collaboration as a force

Tefferi has a notable résumé of research in myeloid disorders, from identifying diagnostic and risk stratification models to disease management. Throughout his career, he has maintained a long-term collaboration and friendship with Tiziano Barbui, MD, founder of the Hematology Department at Papa Giovanni XXIII Hospital in Bergamo, Italy, and Alessandro Vannucchi, MD, professor of hematology and director of the Hematology Department at the University of Florence in Italy.

Barbui first met Tefferi at a meeting at Mayo Clinic more than 30 years ago. Reflecting on that time, he said, “Ayalew Tefferi was a young physician who stood out during that meeting for the sharpness of his questions and comments. I continued to follow his work, which I found very stimulating, and we became friends. The intense scientific collaboration we share and the sincere friendship that has developed between us and with his colleagues are a sign of the deep respect I have for Ayalew. His expertise and his way of approaching problems reveal a rare kind of leadership.”

Vannucchi echoed these sentiments and praised Tefferi’s professional impact and collaborative spirit.

“I have known Dr Tefferi for at least 2 decades, owing to our mutual interest in chronic myeloid neoplasms,” Vannucchi said. “Since then, I had the exciting opportunity to collaborate with him, contributing to pivotal discoveries with impact on patient care that were reported in hundreds of collaborative papers. I appreciated Dr Tefferi’s extensive knowledge of hematology; he is an acute observer, far-seeing, and has an exceptional writing ability.”

Together, the group has worked to improve diagnosis and management of the disease through their research, including assessments of diagnostic criteria^1,2 and current therapies.³

“We call ourselves the Three Musketeers,” Tefferi said. “We’ve had decades of collaboration, and without them, I wouldn’t be who I am now. It’s a wonderful academic collaboration, and it’s ongoing and stronger, because we’re all older, and we’re all wiser.”

Exciting developments in myeloid malignancies

Tefferi is excited and energized by the research developments that have emerged in recent years in his field. He noted that the discovery of the JAK2 V617F mutation “completely revolutionized diagnostics, prognostication, and treatment research and development. This was, by far, the most important contribution.”

Following the discovery of the JAK2 V617F mutation in 2005 by William Vainchenker and other colleagues,^4,5 other JAK-STAT activating mutations in MPNs were subsequently described and enhanced the collaboration between Tefferi and Gary Gilliland, MD, PhD, of Dana-Farber Cancer Institute.⁶

According to Tefferi, the research following the discovery of the JAK2 mutation not only led to the identification of other important mutations, but also to the application of this knowledge in developing targeted therapies.

“I think the JAK2 inhibitors have made a major difference in alleviation of symptoms for many, many, many patients,” he said. “It’s a major, major discovery. Those drugs have helped significantly.” However, these drugs do not modify the natural history of the disease that is currently accomplished only by allogeneic stem cell transplantation.

The World Health Organization and the International Consensus Classification systems, in which Tefferi played a key role, brought together hematopathologists, clinicians, geneticists, and other specialists to develop a common language and comprehensive guidelines for classifying these diseases, which he believes is incredibly important for the field. Tefferi admires the incredible knowledge and work provided by the hematopathology leaders of these formal criteria, including Daniel Arber, MD, from the University of Chicago in Illinois; Attilio Orazi, MD, of Texas Tech University Health Sciences Center in El Paso; and Robert Hasserjian, MD, of Massachusetts General Hospital in Boston.⁷

Becoming an educator and mentor

Tefferi considers one of his biggest contributions to the field to be his role as an educator within his institution, nationally, and internationally. As his early mentors served as role models for him, Tefferi does the same for younger doctors and researchers entering the field.

“Young people interested in deepening their knowledge of polycythemia, myelofibrosis, and chronic myeloid hematologic diseases in general are naturally drawn to Ayalew and aspire to spend…periods at the Mayo Clinic,” Barbui noted. “They tell me about Professor Tefferi and his kindness and about his way of teaching, which reveals an innate ability to truly be a mentor and a giant in hematology. Vannucchi echoed that, saying that Tefferi is “kind, very generous, and always ready to help and support colleagues, particularly the youngest ones.”

“When I first met Dr Tefferi more than 15 years ago, I was extremely impressed,” said John Crispino, PhD, MBA, director of the Division of Experimental Hematology and Wall Street Committee Endowed Chair at St Jude Children’s Research Hospital. “He was already an icon in the field of myeloid malignancies, yet he was excited to embark on a collaboration with me, a scientist who had never studied the MPNs. My interactions with him transformed my approach to medical research and led to many notable discoveries.” These included the clinical benefit of Aurora kinase inhibition in myelofibrosis⁸ as well as identifying AKT as a therapeutic target in MPNs.⁹

As an educator, Tefferi ensures that the lessons he brings to his students extend beyond medicine.

“I always teach my students, in order to be very happy in life, you don’t have to do what you like to do. You have to be very good at [what you do,]” Tefferi said. “I might like playing basketball. OK, but I can’t dunk like Michael Jordan. So, I would be miserable.”

Patient care above all

Through it all, however, Tefferi’s guiding force and what he considers to be his biggest contribution is his unwavering diligence and advocacy for his patients.

“The true giants are our patients. Those are the warriors. They are the best people to be friends with, and it is an honor to be a partner in their journey, no matter how difficult it is,” Tefferi said. “That is my ethos. Everything I do is what [I feel] is right for the patient.” He added that he is “accessible to patients and their doctors at all times, 24/7. That stamina—God gave me that stamina.”

Tefferi believes his work cannot happen in a vacuum and that he is only one part of a patient’s cancer journey.

“Never forget the patients and never forget the unsung heroes—the pathologists, the nurses, the pharmacists,” Tefferi said. “I come to my patients, and I tell them, ‘This is what you have, and this is what we’re going to do.’ And they think I did it all. They think that I am God. No, no, no, no. I talked to my hematopathologist, who took the time to review the material and give me the right diagnosis that I can then go and tell the patient. And in the hospital, everything is done by the nurses. Everything. We go around and spend a few minutes [with patients] here and there, but [the nurses are] there 24 hours a day. These are the unsung heroes. I really feel that they need to be recognized.”

Considering the state of MPN treatment, Tefferi acknowledges that a major challenge remains, which is that science has not yet defeated the underlying cancer itself.

“We can mask the symptoms. We can definitely provide value in that regard. But I don’t think we should spin that around and feel that we have made a biologically credible difference in outcome,” he said.

The goal is to find drugs that specifically target the cancer, much like imatinib (Gleevec) did for chronic myeloid leukemia.

“Everyone’s working very hard,” Tefferi said. “All those [efforts] are coming through in order to find drugs that could specifically target the mutant clones that would make a major difference. But that might take another 100 years; I hope it takes another 20 years instead. We’re getting there, slowly but surely.”

Despite his impact as a clinician and researcher, Tefferi remains grounded—and walking.

“What people need to realize is you have to take care of yourself. Nobody cares about what you did after you die. I mean, really, nobody,” Tefferi said. “I think you owe it to yourself to stay young, to stay strong. That’s why I like the movement. It’s not a waste of time. Your mind is the clearest when you’re just walking and doing nothing. That’s when all the good things come to your mind.”

References

1. Tefferi A, Thiele J, Vannucchi AM, Barbui T. An overview on CALR and CSF3R mutations and a proposal for revision of WHO diagnostic criteria for myeloproliferative neoplasms. Leukemia. 2014;28(7):1407-1413. doi:10.1038/leu.2014.35
2. Barbui T, Thiele J, Vannucchi AM, Tefferi A. Rethinking the diagnostic criteria of polycythemia vera. Leukemia. 2014;28(6):1191-1195. doi:10.1038/leu.2013.380
3. Pardanani A, Vannucchi AM, Passamonti F, Cervantes F, Barbui T, Tefferi A. JAK inhibitor therapy for myelofibrosis: critical assessment of value and limitations. Leukemia. 2011;25(2):218-225. doi:10.1038/leu.2010.269
4. James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434(7037):1144-1148. doi:10.1038/nature03546
5. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365(9464):1054-1061. doi:10.1016/ S0140-6736(05)71142-9
6. MPD gene mutation discovered. MPN Research Foundation. May 3, 2006. Accessed August 7, 2025. https://tinyurl.com/re2tyym6
7. Tefferi A, Thiele J, Orazi A, et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood. 2007;110(4):1092-1097. doi:10.1182/ blood-2007-04-083501
8. Gangat N, Marinaccio C, Swords R, et al. Aurora kinase A inhibition provides clinical benefit, normalizes megakaryocytes, and reduces bone marrow fibrosis in patients with myelofibrosis: a phase I trial. Clin Cancer Res. 2019;25(16):4898-4906. doi:10.1158/1078-0432.CCR-19-1005
9. Fu C, Wen QJ, Marinaccio C, et al. AKT activation is a feature of CALR mutant myeloproliferative neoplasms. Leukemia. 2019;33(1):271-274. doi:10.1038/s41375-018-0224-8