Lymphoma
Leukemia
Cell Therapy
Research

Our Mission

The mission of our department is to advance cures for cancer patients through world-class clinical care and innovative research.
Therefore, we offer the full spectrum of treatments for hematological malignancies and solid cancers and are dedicated to translational and clinical research with a main focus on lymphoma, leukemia and cellular therapies

→ OELLERICH LAB

The research laboratory of Dr. Thomas Oellerich, embedded within the German Cancer Consortium (DKTK) and the Frankfurt Cancer Institute (FCI), is dedicated to unraveling the intricate mechanisms underlying lymphoma and leukemia biology, along with the vision to translate our research findings into clinical advancement. Our focus is the identification of drug targets and predictive biomarkers, the elucidation of therapy resistance mechanisms, and the development of innovative therapeutic approaches, including molecular and cellular therapies. Therefore, we combine deep mechanistic research with cutting-edge technologies such as mass-spectrometry-based proteomics, functional genomics and high-resolution imaging to study innovative tumor models and patient-derived tumors.

→ SERVE LAB

Acute Myeloid Leukemia (AML) is an aggressive type of leukemia, which despite recent therapeutic progress still is fatal in the majority of cases. One important aspect of AML pathophysiology is its aggressive behavior in the bone marrow microenvironment. However, its molecular basis and metabolic mechanisms are still insufficiently understood.
Integrated into the Frankfurt Cancer Institute (FCI) and the German Cancer Consortium (DKTK), our interdisciplinary research laboratory is interested in deciphering targetable mechanisms that lead to clonal dominance and tumor expansion of AML cells. In this context, we are particularly focused on the analysis of metabolic dependencies, clonal hematopoiesis -associated genetic mutations and therapy-induced resistance mechanisms with the aim to develop novel therapeutic options

→ BRANDTS/KOSCHADE LAB

Our research lab, affiliated with the University Cancer Center Frankfurt (UCT) and the Frankfurt Cancer Institute (FCI), works at the interface of acute myeloid leukemia (AML) studying cellular and molecular mechanisms of AML maintenance and therapy resistance. Therefore, we explore the role of autophagy pathways using CRISPR/Cas9, proteomics, metabolic and flow cytometry-based assays. Investigating bone marrow adipocytes (BMAd) as the dominant population of the bone marrow microenvironment, we aim to understand the role of host autophagy pathways.
We also employ various molecular and cellular techniques looking at nongenetic adaptive pathways contributing to AML persistence during chemotherapy.
Additionally, integrating genomic data with phosphoproteomics enhances decision-making in molecular tumor boards and allows us to identify biomarkers for drug response.

→ CREMER LAB

Our research is dedicated to the translation of basic science to the clinic. Acute lymphocytic leukemia (ALL) is the second most common leukemia. Although the traditional multiagent chemotherapy regimens induce high complete remission (CR) rates, many adult patients experience relapse of their disease. Despite the breakthrough advances of antibody-based therapies, the overall long-term survival rate for patients with relapsed or refractory ALL, as well as for certain genetic subtypes is still dismal emphasizing the need for novel, targeted treatment strategies. By applying a multi-omics approach, as well as innovative screening strategies and complementing our results with clinical patient samples and data, our goal is to identify new oncogenic transcriptional networks in acute lymphoblastic leukemia (ALL) which will ultimately lead to new targeted treatment strategies for patients with this disease

→ SCHEICH LAB

Our group focuses on translational cancer research. We are dedicated to advancing knowledge in two specific research fields, lymphoid malignancies and the microbiome in cancer patients. Our overarching objective is to elucidate the fundamental mechanisms contributing to the onset of hematologic malignancies, patients' response to established therapeutic modalities and to find novel therapeutic targets. Through state-of-the art technologies such as CRISPR/Cas9 screens, functional proteomics and super resolution microscopy (dSTORM, SIM) we study lymphoma biology. Paired with the genomic and proteomic analysis of patient derived materials, we study disease development and therapy responses to ultimately improve patient outcomes.

→ RIEGER LAB

The group of Michael Rieger focuses their research on basic mechanisms that control normal and disturbed stem cell fate decisions (self-renewal, differentiation, lineage choice, quiescence, metabolism). Clonal architecture, dominance and competition of stem cells in health and disease are studied. Hematopoietic stem cells and their orchestrated differentiation into blood cell lineages are primarily studied. Eary molecular drivers of clonal dominance and their consequences on interorgan communication and disease progression must be understood for early prevention and treatment of hematologic and non-hematologic diseases. We utilize and develop cutting-edge single cell technologies and bioinformatic analyses and apply them to stem cell systems from mice and humans. MultiOmics single cell sequencing combined with multi-color FACS sorting enable analysis of defined cell identites.

Our Mission

→ OELLERICH LAB

Our research laboratory, embedded within the German Cancer Consortium (DKTK) and the Frankfurt Cancer Institute, is dedicated to unraveling the intricate mechanisms underlying lymphoma and leukemia biology, along with the vision to translate our research findings into clinical advancement. Our focus is the identification of drug targets and predictive biomarkers, the elucidation of therapy resistance mechanisms, and the development of innovative therapeutic approaches, including molecular and cellular therapies. Therefore, we combine deep mechanistic research with cutting-edge technologies such as mass-spectrometry-based proteomics, functional genomics and high-resolution imaging to study innovative tumor models and patient-derived tumors.

→ SERVE LAB

Acute Myeloid Leukemia (AML) is an aggressive type of leukemia, which despite recent therapeutic progress still is fatal in the majority of cases. One important aspect of AML pathophysiology is its aggressive behavior in the bone marrow microenvironment. However, its molecular basis and metabolic mechanisms are still insufficiently understood.
Integrated into the Frankfurt Cancer Institute and the German Cancer Consortium (DKTK), our interdisciplinary research laboratory is interested in deciphering targetable mechanisms that lead to clonal dominance and tumor expansion of AML cells. In this context, we are particularly focused on the analysis of metabolic dependencies, clonal hematopoiesis -associated genetic mutations and therapy-induced resistance mechanisms with the aim to develop novel therapeutic options

→ BRANDTS/KOSCHADE LAB

→ CREMER LAB

→ SCHEICH LAB

→ RIEGER LAB

We focus our research on basic mechanisms that control normal and disturbed stem cell fate decisions (self-renewal, differentiation, lineage choice, quiescence, metabolism). Clonal architecture, dominance and competition of stem cells in health and disease are studied. Hematopoietic stem cells and their orchestrated differentiation into blood cell lineages are primarily studied. Eary molecular drivers of clonal dominance and their consequences on interorgan communication and disease progression must be understood for early prevention and treatment of hematologic and non-hematologic diseases. We utilize and develop cutting-edge single cell technologies and bioinformatic analyses and apply them to stem cell systems from mice and humans. MultiOmics single cell sequencing combined with multi-color FACS sorting enable analysis of defined cell identites.

Research Programs

Our department is embedded in a vibrant research environment, fostering numerous fruitful national and international collaborations. By combining expertise from diverse research sites, we accelerate discoveries in lymphoma, leukemia, and cell therapy research. Through this global network, we are translating cutting-edge findings into clinical advancements.

SFB1530

The Collaborative Research Center 1530 (SFB1530) is a network of internationally visible investigators with highly complementary technical expertise in innovative lymphoma models, cutting-edge genomics and proteomics platforms, comprehensively characterized, large cohorts of lymphoma patients, powerful bioinformatics and a successful clinical trial infrastructure.

The DFG-funded Research Unit FOR5643 (HERZBLUT) comprises a strong team of world-leading experts in the fields of hematology and cardiovascular medicine and emerging junior investigators to pair strong life science and medical research experience with sophisticated technologies and advanced research approaches.

The CARISMa research program for innovative cell therapy research is funded from 2025-2028 and aims to elucidate the molecular pathways controlling CAR T-cell activity and study resistance mechanisms mediated by the tumor microenvironment.

BITeAML

The innovation research program Boost Immuno-Therapy for AML (BITeAML) aims at revolutionizing immunotherapy against acute myeloid leukemia. Prof. Thomas Oellerich will be the overall coordinator.

NEWS

Recently Published

New paper published
in Cancer Cell (06/2026)
by Enssle, Häupl, Qoku et al.

Pathogenesis of diffuse large B cell lymphoma proteogenotypes

The clinical and molecular heterogeneity of diffuse large B cell lymphoma (DLBCL) is incompletely understood. By integrating proteomic, transcriptomic, and genomic data from 478 DLBCL tumors, we identify seven DLBCL proteogenotypes (PGs) reflecting specific pathophysiological features that span known molecular subtypes. PG4 is associated with poor outcome independent of established risk factors such as cell-of-origin, international prognostic index, or genetic features. PG4 contains activated B cell-like and germinal center B cell-like tumors and genetically unclassified cases. It shares a dark-zone-related B cell phenotype and shows enrichment for BTG1 mutations that can activate MYC. Single-cell sequencing and spatial transcriptomics reveal enhanced MYC and TCF3/4 transcriptional activity irrespective of MYC translocations. The PG4 tumor microenvironment is characterized by exhausted CD8⁺ T cells. Our study identifies common oncogenic themes underlying high-risk DLBCL tumors and provides a proteogenomic framework for future diagnostic and therapeutic approaches.

RHOA controls oncogenic B cell receptor signaling in aggressive lymphoma

Diffuse large B cell lymphoma (DLBCL) is characterized by a variety of specific genetic alterations that impact signaling pathway dependencies and therapeutic outcomes. Among the recurrently mutated genes, we identified RHOA, a member of the small GTPase family, as a selective dependency in DLBCL. Here, we show that RHOA function is essential for the survival of ABC DLBCL cells because it sustains oncogenic B cell receptor (BCR) signaling through maintaining a signaling-permissive conformation of the cortical actin network. This enables the formation of active BCR microclusters at the cell surface, ultimately resulting in constitutive, BCR-driven NF-κB survival signaling. Moreover, we found that RHOA controlled endocytosis of the BCR and thereby the assembly of the endolysosomal My–T–BCR multiprotein complex, a central activator of NF-κB consisting of MYD88, Toll-like receptor 9, and the internalized BCR. The recurrent DLBCL-associated RHOA R5W mutation rendered RHOA constitutively active in its GTP-bound state and changed the conformation of the actin network from primarily filamentous actin to globular actin. This altered actin state led to an increase in BCR microcluster formation, amplification of NF-κB signaling, and resistance to inhibitors targeting chronic active BCR signaling. Hence, our study establishes RHOA and its mutant isoforms as critical regulators of oncogenic BCR signaling in DLBCL

Uncovering early gene network changes of human hematopoietic stem cells (HSCs) leading to differentiation induction is of utmost importance for therapeutic manipulation. We employed single cell proteo-transcriptomic sequencing to FACS-enriched bone marrow hematopoietic stem and progenitor cells (HSPCs) from 15 healthy donors. Pseudotime analysis reveals four major differentiation trajectories,which remain consistent upon aging, with an early branching point into megakaryocyte-erythroid progenitors. However, young donors suggest a more productive differentiation from HSPCs to committed progenitors of all lineages. tradeSeq analysis depicts continuous changes in gene expression of HSPC-related genes (DLK1, ADGRG6), and provides a roadmap of gene expression at the earliest branching points. We identify CD273/PD-L2 to be highly expressed in a subfraction of immature multipotent HSPCs with enhanced quiescence. Functional experiments confirm the immune-modulatory function of CD273/PD-L2onHSPCs in regulating T-cell activation and cytokine release. Here, we present a molecular map of early HSPC differentiation across human life.

Diagnosis, prognostic factors, and assessment of ALL in adults: 2024 ELN recommendations from a European expert panel
Working groups of the European LeukemiaNet have published several important consensus guidelines. Acute lymphoblastic leukemia (ALL) has many different clinical and biological subgroups and the knowledge on disease biology and therapeutic options is increasing exponentially. The European Working Group for Adult ALL has therefore summarized the current state of the art and provided comprehensive consensus recommendations for diagnostic approaches, biologic and clinical characterization, prognostic factors, and risk stratification as well as definitions of endpoints and outcomes. Aspects of treatment, management of subgroups and specific situations, aftercare, and supportive care are covered in a separate publication. The present recommendation intends to provide guidance for the initial management of adult patients with ALL and to define principles as a basis for future collaborative research.

Patients with multiple myeloma (MM) routinely receive mRNA-based vaccines to reduce COVID-19-related mortality. However, whether disease- and therapy-related alterations in immune cells and cytokine-responsiveness contribute to the observed heterogeneous vaccination responses is unclear. Thus, we analyzed peripheral blood mononuclear cells from patients with MM during and after SARS-CoV-2 vaccination and breakthrough infection (BTI) using combined whole-transcriptome and surface proteome single-cell profiling with functional serological and T-cell validation in 58 MM patients. Our results demonstrate that vaccine-responders showed a significant overrepresentation of cytotoxic CD4+ T- and mature CD38+ NK-cells expressing FAS+/TIM3+ with a robust cytokine-responsiveness, such as type-I-interferon-, IL-12- and TNF-α-mediated signaling. Patients with MM experiencing BTI developed strong serological and cellular responses and exhibited similar cytokine-responsive immune cell patterns as vaccine-responders. This study can expand our understanding of molecular and cellular patterns associated with immunization responses and may benefit the design of improved vaccination strategies in immunocompromised patients.

Diffuse large B cell lymphoma (DLBCL) is an aggressive, profoundly heterogeneous cancer, presenting a challenge for precision medicine. Bruton’s tyrosine kinase (BTK) inhibitors block B cell receptor (BCR) signaling and are particularly effective in certain molecular subtypes of DLBCL that rely on chronic active BCR signaling to promote oncogenic NF-κB. The MCD genetic subtype, which often acquires mutations in the BCR subunit, CD79B, and in the innate immune adapter, MYD88L265P, typically resists chemotherapy but responds exceptionally to BTK inhibitors.

However, the underlying mechanisms of response to BTK inhibitors are poorly understood. Herein, we find a non-canonical form of chronic selective autophagy in MCD DLBCL that targets ubiquitinated MYD88L265P for degradation in a TBK1-dependent manner. MCD tumors acquire genetic and epigenetic alterations that attenuate this autophagic tumor suppressive pathway. In contrast, BTK inhibitors promote autophagic degradation of MYD88L265P, thus explaining their exceptional clinical benefit in MCD DLBCL.

New paper published
in Cancer Discovery (08/2023)
by Scheich et al.

Glycosylation controls oncogenic B-cell receptor signaling

Diffuse large B-cell lymphoma (DLBCL) can be subdivided into the activated B-cell (ABC) and germinal center B cell–like (GCB) subtypes. Self-antigen engagement of B-cell receptors (BCR) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-κB and PI3 kinase. Constitutive BCR signaling is essential in some GCB tumors but primarily activates PI3 kinase. We devised genome-wide CRISPR–Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-κB and an indicator of proximal BCR signaling in ABC DLBCL. Unexpectedly, inactivation of N-linked protein glycosylation by the oligosaccharyltransferase-B (OST-B) complex reduced IRF4 expression. OST-B inhibition of BCR glycosylation reduced BCR clustering and internalization while promoting its association with CD22, which attenuated PI3 kinase and NF-κB activation. By directly interfering with proximal BCR signaling, OST-B inactivation killed models of ABC and GCB DLBCL, supporting the development of selective OST-B inhibitors for the treatment of these aggressive cancers.

The proteogenomic subtypes of acute myeloid leukemia
Acute myeloid leukemia (AML) is an aggressive blood cancer with a poor prognosis. We report a comprehensive proteogenomic analysis of bone marrow biopsies from 252 uniformly treated AML patients to elucidate the molecular pathophysiology of AML in order to inform future diagnostic and therapeutic approaches. In addition to in-depth quantitative proteomics, our analysis includes cytogenetic profiling and DNA/RNA sequencing. We identify five proteomic AML subtypes, each reflecting specific biological features spanning genomic boundaries. Two of these proteomic subtypes correlate with patient outcome, but none is exclusively associated with specific genomic aberrations. Remarkably, one subtype (Mito-AML), which is captured only in the proteome, is characterized by high expression of mitochondrial proteins and confers poor outcome, with reduced remission rate and shorter overall survival on treatment with intensive induction chemotherapy. Functional analyses reveal that Mito-AML is metabolically wired toward stronger complex I-dependent respiration and is more responsive to treatment with the BCL2 inhibitor venetoclax.

CARISMa Grant (4,8 Mio)
successfully acquired
from 2025-2028!

The collaborative CARISMa research program was successfully acquired for 2025-2028, providing 4.8 million in funding for innovative cell therapy research. The excellence research funding program of the state of Hessen (LOEWE) provides the grant. (Speaker: T. Oellerich)

BITeAML funding successfully acquired
in the 12th DKTK Joint Funding Call
"INNOVATION 2024"

The 12th DKTK Joint Funding Call “INNOVATION 2024” is completed. With the DKTK Joint Funding Program line “INNOVATION”, DKTK supports translational research projects of DKTK scientists for up to three years. At least three DKTK partner sites must be involved in the proposed research project. Maximum budget that can be requested in this call is 1.5 Mio €. A total of 35 proposals have been submitted during this call. (Speaker: T. Oellerich)

German Lymphoma Alliance 2023 Award
in Lymphoma Biology
for Sebastian Scheich ↓

In 2023, Sebastian Scheich was honored with the German Lymphoma Alliance Award in Lymphoma Biology. This recognition celebrates his outstanding dedication and significant contributions to the field of lymphoma biology.
His work has not only deepened the understanding of lymphoma biology but also paved the way for novel approaches in their treatment and therapy. This award underscores his commitment and passion for researching and combating this disease.

Seer’s Proteograph XT
available in our
proteomics lab

We’re happy to implement Seer’s nanoparticle-based Proteograph platform for deep plasma proteomics. Our proteomics team already received extensive application training and is looking forward to work with the instrument. Special thanks got to Ryan, Maik, Dave and Helmut from Seer. Image credits: Maik Pruess, Seer Inc.

Orbitrap Astral
arrived in our
proteomics lab

We’re excited to get in touch with Thermo Fisher’s next-generation Tribrid mass spectrometer. Its exceptional combination of sensitivity, speed, and versatility will boost our proteomics workflows, especially for deep plasma and low-input analyses. The instrument has just been deployed to our facilities and is ready to be installed and put into service.

"Scientist of the Year" Award
for Prof. Dr. Oellerich and
Prof. Dr. Vehreschild

14.11.2025:

Congratulations to Prof. Dr. Thomas Oellerich and Prof. Dr. Maria Vehreschild for receiving the "Scientist of the Year" award by the Goethe University and Kassel-Stiftung for their exceptional research and support of young scientists.

13.04.2026:

Congratulations to Dr. Ariana Jacobs for successfully defending her PhD thesis titled “The Role of RhoA in Activated B-Cell-Like Large B-Cell Lymphoma” with Summa cum laude!

CRC1530 obtains
follow-up funding (10.3M €)
for another 3.5 years

15.05.2026:

CRC1530: Elucidation and targeting of pathogenic mechanisms in B cell malignancies was successfully evaluated, and the German Research Foundation (DFG) approved the second funding period with €10.3M. We highly appreciate this continued support which allows us to further study the mechanisms that drive B cell cancers in order to identify potential novel therapeutic options for patients.

Upcoming Events

Frankfurt Cancer Conference 2026 02-04 September

The Frankfurt Cancer Conference is a three-day on-site meeting of internationally leading cancer researchers as well as junior scientists and clinical oncologists. The main theme of the conference in 2026 is “Translating Paul Ehrlich's Magic Bullet into Novel Targeted Therapies”.

The ongoing translational research activities of the Georg-Speyer-Haus and the University Cancer Center (UCT) Frankfurt and their research consortia such as the German Cancer Consortium (DKTK) in Frankfurt/Mainz and the LOEWE Center Frankfurt Cancer Institute (FCI) provide the framework for the conference. International, national and local research activities will be presented with focus on the following topics:

Tumor Microenvironment
Immunotherapy
Precision Immuno-Oncology
Tumor and Immunometabolism
Microbiome
Cell Plasticity, Senescence and Metastasis
Drug Discovery

LymphomaLeukemiaCell Therapy Research