Head:

Dr. Maximilian Fleischmann
Department of Hematology and Oncology
Clinic for Internal Medicine II
University Hospital Jena
Tel.: +49 (3641) 9-324258
E-mail:

Members

Julia Bechwar (Doctoral Student)
Sanja Bahr (Master’s Student)

Acute Myeloid Leukemia (AML)

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by the clonal expansion of undifferentiated myeloblasts. This leads to progressive bone marrow failure and systemic complications. Despite significant therapeutic advances, the prognosis remains poor, particularly for elderly patients. The genetic complexity and molecular dynamics of AML pose considerable challenges for diagnosis and treatment, necessitating the development of effective, targeted, and personalized therapeutic strategies.

Combination Therapies to Overcome Resistance

Given the limitations of conventional AML therapies, combination treatments are gaining increasing importance. They have the potential to enhance therapeutic efficacy and minimize resistance. By simultaneously inhibiting multiple oncogenic signaling pathways, synergistic effects can often be achieved, leading to improved therapeutic responses.

Preclinical studies from our research group have demonstrated that combining different compounds can overcome PTPN11 mutations, which confer resistance to Venetoclax therapy. Furthermore, combinations of novel agents such as Menin inhibitors (Revumenib) and Tamibarotene (RARalpha agonist) exhibit synergistic and differentiation-inducing effects.

3D Microfluidic Tumor-on-Chip Model

A major challenge in translational AML research is the development of physiologically relevant preclinical models that accurately mimic the bone marrow microenvironment and enable realistic drug testing. The ex vivo cultivation of primary mononuclear cells (MNCs) is often limited by rapid differentiation and apoptosis, restricting their application for drug testing and mechanistic studies.

To address this challenge, we are developing a 3D microfluidic tumor-on-chip platform for the cultivation of primary AML cells as part of a collaborative project. This innovative model aims to replicate the bone marrow stem cell niche, enhance cell viability, and enable physiologically relevant pharmacological evaluation.

Collaboration with the Proteomics Research Group

We maintain a close collaboration with the Proteomics Research Group, led by Junior Professor Dr. Florian Meier-Rosar, to conduct proteomic and phosphoproteomic analyses on primary AML patient samples. These studies aim to characterize novel prognostic and therapeutic biomarkers and identify protein signatures contributing to resistance development.

Selected Publications 

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

German José Carreras Leukemia Foundation
Institute and Center for Clinical Research (IZKF)