apl. Prof. Dr. med. Lüder H. Meyer
Ulm University Medical Center
Department of Pediatrics and Adolescent Medicine
Eythstr. 24 (Research Lab, House 16)
89075 Ulm, Germany
phone: +49-731-500 57254 or -57261
fax: +49-731-500 57042
Among all pediatric cancers, acute lymphoblastic leukemia (ALL) is the most common malignant disease in childhood and adolescence. Over the past decades, substantial achievements have been made resulting in successful treatment of pediatric ALL and cure rates of more than 80%. Despite this success in pediatric oncology, therapy fails in about 20% of the patients leading to reoccurrence of the disease associated with clearly reduced prognosis and outcome. However, the majority of patients encountering relapse are not identified using the currently available risk markers and extramedullary leukemia manifestation outside the hematopoietic system as for example in the central nervous system remains a diagnostic and therapeutic challenge. Moreover, although generally well tolerated, anti-leukemia therapies bear the risk of late sequelae and side effects, in particular for intensified treatment in relapse situations. These problems and limitations clearly highlight the need for less toxic treatment modalities including directed therapies acting on identified targets and improved risk stratification.
In our Leukemia Research Group, the main interests focus on acute lymphoblastic leukemia (ALL). In our work, we want to better understand leukemia biology and to analyze and characterize molecular mechanisms of disease initiation, development and manifestation. Based on our findings, we aim to investigate and develop novel therapeutic approaches like evaluation of new risk markers and new therapeutic agents including preclinical validation in corresponding model systems. By combining comprehensive molecular and functional analyses, we characterize leukemia-specific biological mechanisms and try to identify possible starting points for new therapy strategies for leukemia. Moreover, we have established and refined a leukemia model that mimics the disease seen in patients thus allowing to investigate different aspects of disease biology but also evaluate new treatment modalities pre-clinically and have provided evidence for a good efficacy of several substances alone and in combination with conventional chemotherapy against different subgroups and manifestations of ALL.
- Wang F, Demir S, Gehringer F, Osswald CD, Seyfried F, Enzenmüller S, Eckhoff SM, Maier T, Holzmann K, Debatin KM, Wirth T*, Meyer LH*, Ushmorov A*. Tight regulation of FOXO1 is essential for maintenance of B-cell precursor acute lymphoblastic leukemia. Blood. 2018 Jun 28; 131(26):2929-2942. (*joint last authorship)
- Trentin L, Queudeville M, Eckhoff SM, Hasan N, Münch V, Boldrin E, Seyfried F, Enzenmüller S, Debatin KM, Meyer LH. Leukemia reconstitution in vivo is driven by cells in early cell cycle and low metabolic state. Haematologica. 2018 Jun; 103(6):1008-1017.
- Münch V, Trentin L, Herzig J, Demir S, Seyfried F, Kraus JM, Kestler HA, Köhler R, Barth TFE, Te Kronnie G, Debatin KM, Meyer LH. Central nervous system involvement in acute lymphoblastic leukemia is mediated by vascular endothelial growth factor. Blood. 2017 Aug 3; 130(5):643-654.
- Köhrer S, Havranek O, Seyfried F, Hurtz C, Coffey GP, Kim E, Ten Hacken E, Jäger U, Vanura K, O'Brien S, Thomas DA, Kantarjian H, Ghosh D, Wang Z, Zhang M, Ma W, Jumaa H, Debatin KM, Müschen M, Meyer LH, Davis RE, Burger JA. Pre-BCR signaling in precursor B-cell acute lymphoblastic leukemia regulates PI3K/AKT, FOXO1 and MYC, and can be targeted by SYK inhibition. Leukemia. 2016 Jun; 30(6):1246-54.
- Schirmer M, Trentin L, Queudeville M, Seyfried F, Demir S, Tausch E, Stilgenbauer S, Eckhoff SM, Meyer LH, Debatin KM. Intrinsic and chemo-sensitizing activity of SMAC-mimetics on high-risk childhood acute lymphoblastic leukemia. Cell Death Dis. 2016 Jan 14; 7:e2052.
- Hasan MN, Queudeville M, Trentin L, Eckhoff SM, Bronzini I, Palmi C, Barth T, Cazzaniga G, te Kronnie G, Debatin KM, Meyer LH. Targeting of hyperactivated mTOR signaling in high-risk acute lymphoblastic leukemia in a pre-clinical model. Oncotarget. 2015 Jan 30; 6(3):1382-95.
- Frishman-Levy L, Shemesh A, Bar-Sinai A, Ma C, Ni Z, Frenkel S, Muench V, Bruckmueller H, Vokuhl C, Debatin KM, Eckert C, Stanulla M, Schrappe M, Campbell KS, Loewenthal R, Schewe DM, Hochman J, Meyer LH, Kaufman D, Cario G, Porgador A, Izraeli S. Central nervous system acute lymphoblastic leukemia: role of natural killer cells. Blood. 2015 May 28; 125(22):3420-31.
- Meyer LH, Eckhoff SM, Queudeville M, Kraus JM, Giordan M, Stursberg J, Zangrando A, Vendramini E, Möricke A, Zimmermann M, Schrauder A, Lahr G, Holzmann K, Schrappe M, Basso G, Stahnke K, Kestler HA, Te Kronnie G, Debatin KM. Early relapse in ALL is identified by time to leukemia in NOD/SCID mice and is characterized by a gene signature involving survival pathways. Cancer Cell. 2011 Feb 15; 19(2):206-17.