Principal Investigator
Director of Department I of Internal Medicine
Advances in understanding the pathogenesis of chronic lymphocytic leukemia and a clear commitment to the rapid implementation of this knowledge in the clinics have dramatically changed management of CLL and improved clinical outcome for patients.
Our laboratory has a long-term interest in studying oncogenic signaling events in CLL and investigating the mechanisms that trigger leukemic development through their interaction with the cancer microenvironment. Moreover, our group benefits from a strong clinical trial portfolio of the German CLL Study Group as headed by Michael Hallek that facilitates the translation of novel ideas and concepts into therapeutic reality.
The overall goal of our research is to substantially increase the cure rate of chronic lymphocytic leukemia by a holistic approach that elaborates a comprehensive inventory of the clonal dynamics of this leukemia in patients and in laboratory models.
This research group is investigating the development of novel therapeutic concepts. One approach to treatment of the future is the use of molecules targeting specific pathways in combination with monoclonal antibodies to interrupt leukemogenic signaling pathways. Combinations of specific therapeutics are applied to specific subgroups of patients in an increasingly personalized way. As a prerequisite, the careful genetic analysis of leukemia cells usually determines treatment, from a watch-and-wait strategy to immediate therapy with either chemoimmunotherapy or the combined use of targeted agents. The goal of our group is clearly to optimize therapy to allow CLL patients to gain a normal life expectancy with a good quality of life.
Prof. Hallek’s laboratory has a long-term interest to study oncogenic signaling events in CLL. More recently, the laboratory has decoded the influence of macrophage migration inhibitory factor (MIF) and its putative receptors, CD 74 and CD 44, on leukemic development. MIF appears to have a strong effect on leukemic development: progression is delayed considerably in the absence of MIF, therapy increases survival time of CLL-carrying mice. In clinical trials, the group has shown the impact of B-cell-receptor signaling pathway inhibitors and antibodies to induce clinical remissions of this leukemia.
CLL is at the forefront of research efforts in this present innovative era in cancer medicine that is currently providing many new cancer drugs with promising efficacy. The advent of several, targeted therapies for CLL and the availability of novel analytical tools such as next generation sequencing has provided major ingredients for the creation of targeted anti-leukemic therapies. These advances allow testing of a probabilistic approach, which navigates the cancer patient through molecularly targeted therapies, thus preventing the onset of resistance by using a comprehensive array of cutting-edge technologies. The discoveries made by this approach will be used in a systematic and rapid translation of discoveries into clinical application.
Our specific research aims include:
Al-Sawaf O, Zhang C, Tandon M, Sinha A, Fink AM, Robrecht S, Samoylova O, Liberati AM, Pinilla-Ibarz J, Opat S, Sivcheva L, Le Dû K, Fogliatto LM, Niemann CU, Weinkove R, Robinson S, Kipps TJ, Tausch E, Schary W, Ritgen M, Wendtner CM, Kreuzer KA, Eichhorst B, Stilgenbauer S, Hallek M, Fischer K. Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020 Sep;21(9):1188-1200. doi: 10.1016/S1470-2045(20)30443-5. PMID: 32888452.
Kurtz DM, Esfahani MS, Scherer F, Soo J, Jin MC, Liu CL, Newman AM, Dührsen U, Hüttmann A, Casasnovas O, Westin JR, Ritgen M, Böttcher S, Langerak AW, Roschewski M, Wilson WH, Gaidano G, Rossi D, Bahlo J, Hallek M, Tibshirani R, Diehn M, Alizadeh AA. Dynamic Risk Profiling Using Serial Tumor Biomarkers for Personalized Outcome Prediction. Cell. 2019 Jul 25;178(3):699-713.e19. doi: 10.1016/j.cell.2019.06.011. Epub 2019 Jul 4. PMID: 31280963; PMCID: PMC7380118.
Fischer K, Al-Sawaf O, Bahlo J, Fink AM, Tandon M, Dixon M, Robrecht S, Warburton S, Humphrey K, Samoylova O, Liberati AM, Pinilla-Ibarz J, Opat S, Sivcheva L, Le Dû K, Fogliatto LM, Niemann CU, Weinkove R, Robinson S, Kipps TJ, Boettcher S, Tausch E, Humerickhouse R, Eichhorst B, Wendtner CM, Langerak AW, Kreuzer KA, Ritgen M, Goede V, Stilgenbauer S, Mobasher M, Hallek M. Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions. N Engl J Med. 2019 Jun 6;380(23):2225-2236. doi: 10.1056/NEJMoa1815281. Epub 2019 Jun 4. PMID: 31166681.
Nguyen PH, Niesen E, Hallek M. New roles for B cell receptor associated kinases: when the B cell is not the target. Leukemia. 2019 Mar;33(3):576-587. doi: 10.1038/s41375-018-0366-8. Epub 2019 Jan 30. PMID: 30700840.
Principal Investigator
Director of Department I of Internal Medicine