First person: Ali Bazarbachi, MD, PhD: The professor at the American University of Beirut has advanced the treatment of leukemia and cancer research in the Middle East and worldwide.

Abstract

Civil war in Lebanon forced him to leave his country at the age of 16 years, but Ali Bazarbachi, MD, PhD, never stopped hoping to return. When he finally did, he helped to pioneer cancer research and treatment efforts that have made a significant impact in the Middle East and throughout the world. Currently, Dr. Bazarbachi serves as professor of hematology and oncology; professor of anatomy, cell biology, and physiological sciences; associate dean for basic research; and director of the bone marrow transplantation program at the American University of Beirut (AUB). His research focuses on developing targeted therapies for leukemia and lymphoma and bone marrow transplantation. Among the many national and international prizes and awards he has garnered over the years are the French Ligue Nationale Contre le Cancer Prize for Cancer Research, the Hafez Kobeissi Prize for Excellence in Scientific Research, and the 2008 award of the French National Academy of Medicine. “Ali was one of my first and most brilliant fellows,” says Hugues de Thé, MD, PhD, professor of molecular oncology at the College de France and a physician at St. Louis Hospital in Paris. “He deserves special credit for developing cutting-edge clinical and translational research in a difficult environment with frequent unrest and threats.” Dr. de Thé continues to collaborate with Dr. Bazarbachi in numerous research arenas, including adult T-cell leukemia (ATL) and acute myeloid leukemia (AML), and he is effusive in his admiration for his colleague. “When he has an idea, he never stops until we finalize and publish that research,” Dr. de Thé says. “That is very stimulating.” The habit of perseverance began at an early age. As a young man growing up in Tripoli in Lebanon, Dr. Bazarbachi was fascinated by scientific discoveries and mathematics. Even after the civil war in Lebanon forced him to move to France in 1981, he continued to pursue his interests in the field. He earned his medical and doctoral degrees and completed his residency and fellowship training at the University of Paris VII. (His sister and 2 brothers followed in his footsteps and subsequently earned their medical degrees as well.) Dr. Bazarbachi was especially drawn to hematology. The field appeared to lead the way in pioneering scientific discoveries, partly due to the relative ease of access to human blood samples. “I was fascinated by the blood cancers such as leukemia and lymphoma, and how a normal bone marrow cell would become a malignant cell,” he says. “I completed my PhD in the molecular and cellular basis of oncogenesis in parallel to my residency in hematology/oncology.” After serving 2 years on the junior faculty at the University of Paris VII, Dr. Bazarbachi turned his attention back to his homeland of Lebanon. It was 1996, the civil war had ended, and he was eager to return. He would not have done so, however, had he not been able to join AUB. The prestigious university, established more than 150 years ago, was “by far the leading academic medical center between Italy and China,” Dr. Bazarbachi says. “The challenge is not only to do good science in Western Europe, North America, or Japan, but to do it in your own country.” With that mission in mind, he has proceeded to conduct groundbreaking research in several areas. The first was in the treatment of ATL, a disease that has had an extremely poor prognosis. Dr. Bazarbachi led an international research network that made a key discovery: By targeting the main driver of ATL, namely the human T-lymphotropic virus type I (HTLV-1) retrovirus, they could dramatically improve survival rates with a combination of the antiviral agents zidovudine and interferon-α.1 The group published its findings, a worldwide metaanalysis, in the Journal of Clinical Oncology in 2010. The outlined treatment, which now is the standard of care for patients with ATL, increased 5-year survival rates from 10% to nearly 50%. Today, Dr. Bazarbachi and his colleagues continue their eff orts to improve on those survival rates through a variety of research eff orts. They demonstrated, for example, that ATL-derived cells are addicted to continuous expression of the viral oncoprotein Tax, indicating that Tax degradation underlies clinical responses in mice and patients.2 Furthermore, they demonstrated that treatment with arsenic/interferon targets Tax, which could lead to greater survival among patients with ATL. Although this treatment is not yet part of international guidelines, it currently is being tested in ongoing clinical trials, he reports. “The aim is not only to further improve survival rates but also to help people remain alive without having to continue treatment for years,” Dr. Bazarbachi says. In building on their discoveries, the physician and his colleagues demonstrated that arsenic-based targeted therapy can lead to degradation of the nucleophosmin 1 (NPM-1) mutation, which is present in approximately 30% of patients with AML.3 Currently, Dr. Bazarbachi is working to develop a large clinical trial that will demonstrate the eff ectiveness of combining this targeted treatment with chemotherapy in patients with AML who have this mutation. Reflecting on the significance of these discoveries, Dr. Bazabachi says, “We are proud to give another image of Lebanon than what you see in the news.” He also acknowledges the ongoing challenges that his research team faces at AUB, most notably the small number of funding opportunities available in Lebanon. Thankfully, intramural funding from AUB as well as support from the Lebanese National Council for Scientific Research have helped. Another challenge is the small number of research scientists in Lebanon but, “We have overcome that by having a very strong group at AUB and also collaborating with an international network of scientists,” Dr. Bazarbachi says. The university has undergone tremendous changes since Dr. Bazarbachi first came aboard in the 1990s, at which time there were few modern laboratories. Over the course of a decade, AUB has established core laboratories, enabling faculty to perform basic research. A new administration took charge of the AUB medical school in 2009, and with this change came a remodeling that included brand-new facilities with high-tech laboratory equipment. In part due to these changes, a “reverse brain drain” is occurring, with AUB attracting promising and established investigators who previously left Lebanon for major Western universities. Simultaneously, Dr. Bazabachi has noted that outstanding students from throughout the region are drawn to the university because of its highly recognized facilities, scientists, and research accomplishments. Having worked on developing therapies for ATL since 1989, Dr. Bazarbachi does not want to retire before patients are cured of the disease. In addition, he hopes to see worldwide targeted therapy and precision medicine applications for both leukemia and lymphoma. Last, he hopes to help transform bone marrow transplantation from a treatment currently associated with high mortality and toxicity to “a platform of adoptive immunotherapy followed by targeted therapy posttransplantation, increasing efficacy and reducing both toxicity and mortality of transplants.” In the meantime, his ongoing eff orts include leading “a group of outstanding scientists who will continue on this mission.” When not pursuing these goals, Dr. Bazarbachi enjoys spending time with his wife and his children, who are carrying on the family tradition of pursuing careers in the sciences. He proudly reports that his eldest son, aged 24 years, is finishing his last year of medical school at AUB and currently is doing a rotation at The University of Texas MD Anderson Cancer Center in Houston; his 19-year-old daughter is studying psychology at AUB; and his 16-year-old son, who is still in high school, has set his sights on becoming an engineer.