Impact of intrinsic and extrinsic immune cell signaling on chronic lymphocytic leukemia
Dr. rer. nat. Maike Buchner
School of Medicine
Technical University of Munich
Institute of Clinical Chemistry and Pathobiochemistry(link is external)
TranslaTUM(link is external)
Project Summary
Chronic lymphocytic leukemia (CLL) is characterized by an expansion of monoclonal B cells that carry autoreactive B cell receptors and exerts complex alterations within the associated immune cell compartment. Autoreactive B cells would normally undergo negative selection. The proposal aims to define whether mutations that activate NF-κB signaling, in particular MyD88 and Notch1, inhibit negative selection and thereby allow autoreactive B lymphocytes to transform to CLL. Furthermore, this study aims to elucidate the role of NF-κB activation via innate immune receptors in the myeloid cell compartment within the CLL microenvironment.
A research team at the Technical University of Munich (TUM) has now found a possible cause for these self-destructive immune system attacks: a hyperactive RANK protein on the surface of B cells.
Image: Andreas Heddergott / TUM
Ecker, V., Brandmeier, L., Stumpf, M., Giansanti, P., Moreira, A.V., Pfeuffer, L., Fens, M., Lu, J., Kuster, B., Engleitner, T., Heidegger, S., Rad, R., Ringshausen, I., Zenz, T., Wendtner, C.M., Muschen, M., Jellusova, J., Ruland, J., Buchner, M. (2023). Cell Rep 42, 113017.
DOI:10.1016/j.celrep.2023.113017(link is external)
Zecha, J., Bayer, F. P., Wiechmann, S., Woortman, J., Berner, N., Müller, J., Schneider, A., Kramer, K., Abril-Gil, M., Hopf, T., Reichart, L., Chen, L., Hansen, F. M., Lechner, S., Samaras, P., Eckert, S., Lautenbacher, L., Reinecke, M., Hamood, F., Prokofeva, P., Vornholz, L., Falcomatà, C., Dorsch, M., Schröder, A., Venhuizen, A., Wilhelm, S., Médard, G., Stoehr, G., Ruland, J., Grüner, B. M., Saur, D., Buchner, M., Ruprecht, B., Hahne, H., The, M., Wilhelm, M. & Kuster, B. (2023). Science, 380, 93-101.
DOI:10.1126/science.ade3925(link is external)
Ecker, V., Stumpf, M., Brandmeier, L., Neumayer, T., Pfeuffer, L., Engleitner, T., Ringshausen, I., Nelson, N., Jucker, M., Wanninger, S., Zenz, T., Wendtner, C., Manske, K., Steiger, K., Rad, R., Muschen, M., Ruland, J., Buchner, M. (2021). Nat Commun 12, 3526.
DOI:10.1038/s41467-021-23752-2(link is external)
Sadras, T., Martin, M., Kume, K., Robinson, M. E., Saravanakumar, S., Lenz, G., Chen, Z., Song, J. Y., Siddiqi, T., Oksa, L., Knapp, A. M., Cutler, J., Cosgun, K. N., Klemm, L., Ecker, V., Winchester, J., Ghergus, D., Soulas-Sprauel, P., Kiefer, F., Heisterkamp, N., Pandey, A., Ngo, V., Wang, L., Jumaa, H., Buchner, M., Ruland, J., Chan, W. C., Meffre, E., Martin, T., Muschen, M. (2021). Mol Cell 81, 2094-2111 e2099.
DOI:10.1016/j.molcel.2021.03.043(link is external)
Alankus, B., Ecker, V., Vahl, N., Braun, M., Weichert, W., Macher-Goppinger, S., Gehring, T., Neumayer, T., Zenz, T., Buchner, M., Ruland, J. (2021). J Exp Med 218.
DOI:10.1084/jem.20200517(link is external)
Park, E., Chen, J., Moore, A., Mangolini, M., Santoro, A., Boyd, J. R., Schjerven, H., Ecker, V., Buchner, M., Williamson, J. C., Lehner, P. J., Gasparoli, L., Williams, O., Bloehdorn, J., Stilgenbauer, S., Leitges, M., Egle, A., Schmidt-Supprian, M., Frietze, S., Ringshausen, I. (2020). Sci Transl Med 12.
DOI:10.1126/scitranslmed.aax9340(link is external)