Prof. Dr. Michael Hallek

Chronic lymphocytic leukemia (CLL) is caused by the concerted action of genetic events in the cancer cell and of a sustained, chronic inflammation and subsequent stimulation of immune cells. This contributes to leukemogenesis, typically in older patients. The team of Prof. Dr. Michael Hallek investigates the signals that influence immune cells in the tumor microenvironment to support the development of leukemia. The aim of the group is to understand the mechanisms by which genetic driver mutations interact with cancer-supporting factors of the microenvironment to initiate and enhance leukemic development. The long-term goal is the development of improved therapeutic concepts for leukemia patients.

Our research: Chronic lymphocytic leukemia (B-CLL), the typical leukemia of the elderly, is triggered by an interaction of genetic aberrations in B cells and their microenvironment. In this disease, leukemic development can be seen as the result of a chronic inflammation and stimulation of the immune system. These events prevent the apoptosis of clonal, long-lived CD5+ B cells which subsequently accumulate and facilitate the development of subsequent mutations. The team of Prof. Hallek investigates the mechanisms that trigger leukemic development through their interaction with the cancer microenvironment. In particular, the group aims to understand which specific pathways are critical for the dialogue between leukemic cells and microenvironmental cells and could serve as targets for novel treatments. Moreover the group is benefitting from a strong clinical trial portfolio of the German CLL study group (head Michael Hallek), that facilitates the translation of novel ideas and concepts into therapeutic reality.

Our successes: 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 increasing 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.

Our goals: 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.

Our methods/techniques: The team employs a very wide range of laboratory and clinical research methods, including laboratory testing with cell cultures and a variety of different leukemia mouse models. The resultant treatment concepts are being tested in small to large-scale clinical trials (first in man, phase I to III). The laboratory and the GCLLSG, currently one of the largest study groups on this disease world-wide (www.dcllsg.de), cooperate with many other centers in world-wide. Clinical trials currently assess studies therapeutic success and form the basis for determining clinical guidelines.