| CNRS Networks cnrs I international w 34 magazine Molecular Oncology A long and fruitful collaboration between two researchers fighting a rare form of leukemia has matured into a French-Lebanese joint laboratory. French-Lebanese Collaboration to Fight Leukemia By Alexander Hellemans The long-standing collaboration between Hugues de Thé, professor of molecular biology at Paris-VII University,1 and Ali Bazarbachi, professor of medicine at the American University of Beirut (Lebanon), has led to the creation in 2012 of the International Associated Laboratory (LIA) on leukemia targeted treatment. Both scientists are principal investigators of this new LIA dedicated to the development of a treatment for Adult T-cell leukemia (ATL), each leading a research team of four people in their respective universities. The two researchers started working together in the early 1990s. Bazarbachi, then a medical resident in Paris and a student of de Thé, focused his research on the HTLV-1 virus, which causes ATL. “After he left my lab to open his own in Beirut, we kept collaborating. It’s been almost 20 years,” recalls de Thé. ATL was identified in 1981 as the first cancer induced by a retrovirus. As with other diseases caused by retroviruses, like AIDS, it proved notoriously difficult to treat. “Chemotherapy is not a very efficient treatment, and tumors relapse, especially in leukemic forms,” says de Thé. “In 1998, Ali made the first breakthrough by observing that HTLV-1 infected cells were highly sensitive to interferon and arsenic,” the researcher continues. Furthermore, he showed that the combination of arsenic and interferon acted primarily on HTLV-1 infected cells, but not on other leukemia cells. “A few years later, we both discovered that this combination could induce the degradation of a specific viral protein called Tax, the main driver of viral replication. There were hints that Tax was essential in the proliferation of HTLVassociated leukemias,” says de Thé. The year 2009 marked a turning point in their collaboration when a team led by Bazarbachi reported a phase-2 clinical study in which ten patients with chronic ATL were treated with a combination of arsenic trioxide, interferon-alpha, and zidovudine. “We obtained a response in all patients, with complete remission in seven of them, and very good partial response in two,” reports Bazarbachi. Recently, another trial which will soon be published was performed with patients with ATL lymphoma, a more severe condition. It revealed that the combination including arsenic is also effective in fighting this disease. “What we really need to do now is carry out a randomized trial to confirm this result,” says de Thé. The two teams have co-published more than 40 papers in high-flying medical journals. “Our collaboration is very productive, both in terms of publication numbers and impact factor,” says Bazarbachi. “Moreover, our joint project has been funded by several grants that have proved decisive to continue our research. Some aspects of the role of Tax still need investigating, especially the persistence of oncogenes in the infected cells at the later stages of leukemia development,” he concludes. With this collaboration now structured in an LIA, it will be easier to enroll post-docs, as well as obtain funding to pursue their goal. The American University of Beirut recently initiated its own PhD program in medical research, which, coupled with this new LIA, should strengthen cooperation between the two institutions. 01. Pathologie et virologie moléculaire (CNRS / Inserm / Université Paris-VII). Contact information: Pathologie et virologie moléculaire, Paris. Hugues de Thé > dethe@univ-paris-diderot.fr American University of Beirut. Ali Bazarbachi > bazarbac@aub.edu.lb 01 The American University of Beirut campus (Lebanon). 02 Scanning electron micrograph of a human T-lymphocyte (blue) infected with the HTL V-1 virus (red). © offic e of communica tions /AUB © PHOTOTAKE/KUNKEL/BSIP 02 01
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