Group Leader:

Dr. med. Maximilian Fleischmann
Department of Hematology and Oncology
Department of Internal Medicine II
Jena University Hospital

tel.: +49 (3641) 9-324258
email:

Team Members

• Julia Bechwar (PhD candidate)
• Sanja Bahr (MSc student)
• Lenny-Joseph Schwietzer (MSc student)
• Hannah Schieder (MD candidate)

Research Focus

Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy characterized by the clonal expansion of immature myeloid progenitor cells, leading to progressive bone marrow failure and systemic complications. Despite substantial advances in molecular diagnostics and the development of targeted therapies, prognosis, particularly in elderly patients, remains poor. The genetic complexity of AML poses major challenges to durable disease control and highlights the need for improved and individualized therapeutic approaches.

The research of our group focuses on the investigation of cellular mechanisms associated with treatment response and therapy tolerance in AML. Using functional cell-based models in combination with molecular analytical methods, we study adaptive survival processes in leukemic cells under therapeutic pressure.

Combination Therapies and Treatment Resistance

The limited long-term efficacy of many current AML therapies has significantly increased interest in combination strategies aimed at overcoming resistance. While targeted agents may induce initial responses, compensatory survival processes are frequently activated, contributing to therapy tolerance and subsequent disease relapse. The simultaneous modulation of multiple signaling pathways through drug combinations offers the potential to achieve synergistic effects and improve therapeutic efficacy.

Our work aims to systematically investigate resistance mechanisms at the cellular level and to identify rational combination strategies that address these adaptive processes. To this end, we establish and characterize leukemia cell models that reflect therapy-adapted disease states. These models enable functional and molecular analyses of altered signaling networks and serve as platforms for evaluating novel therapeutic concepts.

Autophagy and Cellular Stress Responses

Autophagy is a central cellular stress-response mechanism that supports metabolic adaptation, survival under therapeutic pressure, and long-term persistence of leukemic cells. Increasing evidence suggests a key role of autophagy in therapy tolerance and disease relapse in AML. Accordingly, a major focus of our research is the investigation of autophagy-dependent survival mechanisms and their therapeutic modulation within combination treatment approaches.

Determinants of Treatment Response and Toxicity

The interindividual variability in therapeutic response as well as therapy-associated toxicities during AML treatment with vidaza and venetoclax represents a significant clinical challenge. Our research aims to investigate the robustness of healthy hematopoiesis in the context of anti-leukemic therapies and thereby contribute to improved therapy guidance and optimization.

Advanced Preclinical Models

A major limitation of translational leukemia research is the lack of physiologically relevant preclinical models that adequately recapitulate the bone marrow microenvironment. To address this challenge, our group is involved in the development of a three-dimensional, microfluidic tumor-on-chip culture system for the cultivation of primary AML cells. This interdisciplinary project is conducted in collaboration with Carl Zeiss Microscopy GmbH, Microfluidic ChipShop GmbH, the Institut für Bioprozess- und Analysenmesstechnik e. V., and Dyomics GmbH, and is funded by the Thuringian Development Bank.

Proteomics and Systems Biology Analyses

Our research is complemented by close collaboration with the Functional Proteomics Group led by jun. Prof. Dr. Florian Meier-Rosar. Within this collaboration, proteomic and phosphoproteomic analyses are performed on primary AML patient samples, to identify and characterize novel prognostic and therapy-relevant biomarkers and protein patterns associated with resistance development.

Selected Publications 

2026

Fleischmann M, Hansen O, Voigtländer D, Bechwar J, Schwietzer LJ, Bahr S, Schnetzke U, Fischer M, Heidel FH, Schnöder TM, Müller JP, Hochhaus A, Scholl S. Targeting MCL-1 and MAPK overcomes venetoclax resistance in FLT3-ITD–positive AML cells harboring activating PTPN11 (SHP-2) mutations. Br J Haematol. Accepted for publication.

2025

Papayannidis C, Schnetzke U, Fleischmann M, De La Fuente Burguera A, Metzeler K, Lane M, Zhou L, Hamdy A, Cerchione C. Preliminary pharmacokinetic and MRD results from AML patients treated with 7- and 14-day dosing schedule of emavusertib added to combination therapy with azacitidine and venetoclax. Blood. 2025;146(Suppl 1):5201. Poster presented at: ASH Annual Meeting 2025; Orlando, FL.

2024

Fleischmann M, Jentzsch M, Brioli A, Eisele F, Frietsch JJ, Eigendorff F, Tober R, Schrenk KG, Hammersen JF, Yomade O, Hilgendorf I, Hochhaus A, Scholl S, Schnetzke U. Azacitidine in combination with shortened venetoclax treatment cycles in patients with acute myeloid leukemia. Ann Hematol. 2024 Oct 25. doi: 10.1007/s00277-024-06048-5.

Fleischmann M, Bechwar J, Voigtländer D, Fischer M, Schnetzke U, Hochhaus A, Scholl S. Synergistic Effects of the RARalpha Agonist Tamibarotene and the Menin Inhibitor Revumenib in Acute Myeloid Leukemia Cells with KMT2A Rearrangement or NPM1 Mutation. Cancers. 2024; 16(7):1311. https://doi.org/10.3390/cancers16071311

Arends CM, Kopp K, Hablesreiter R, Estrada N, Christen F, Moll UM, Zeillinger R, Schmitt WD, Sehouli J, Kulbe H, Fleischmann M, Ray-Coquard I, Zeimet A, Raspagliesi F, Zamagni C, Vergote I, Lorusso D, Concin N, Bullinger L, Braicu EI, Damm F. Dynamics of clonal hematopoiesis under DNA-damaging treatment in patients with ovarian cancer. Leukemia. 2024 Jun;38(6):1378-1389. doi: 10.1038/s41375-024-02253-3.

2022

Fleischmann M, Schnetzke U, Frietsch JJ, Sayer HG, Schrenk K, Hammersen J, Glaser A, Hilgendorf I, Hochhaus A, Scholl S. Impact of induction chemotherapy with intermediate-dosed cytarabine and subsequent allogeneic stem cell transplantation on the outcome of high-risk acute myeloid leukemia. J Cancer Res Clin Oncol. 2021 Jul 23. doi: 10.1007/s00432-021-03733-0.

Fleischmann, M., Schnetzke, U., Hochhaus, A. et al. Ziele und Optionen der palliativen Therapie der akuten myeloischen Leukämie. Onkologie 28, 483–491 (2022). https://doi.org/10.1007/s00761-022-01151-6

2021

Fleischmann M, Schnetzke U, Hochhaus A, Scholl S. Management of Acute Myeloid Leukemia: Current Treatment Options and Future Perspectives. Cancers (Basel). 2021 Nov 16;13(22):5722. doi: 10.3390/cancers13225722.

Fleischmann M, Fischer M, Schnetzke U, Fortner C, Kirkpatrick J, Heidel FH, Hochhaus A, Scholl S. Modulation of FLT3-ITD Localization and Targeting of Distinct Downstream Signaling Pathways as Potential Strategies to Overcome FLT3-Inhibitor Resistance. Cells. 2021 Nov 3;10(11):2992. doi: 10.3390/cells10112992.

Funding

Our work is supported by funding from national and institutional programs, including:

• German José Carreras Leukemia Foundation
• Interdisciplinary Center for Clinical Research (IZKF)
• Else Kröner Graduate Program “Autophagy – Recycling, Repair, Defense (AURA)”
• Thuringian Development Bank (TAB)