The origin of evil: stem cell-like cells are the reason for relapses of blood cancer in children and adolescents

Stem cell-like leukemia cells are responsible for relapses in children and adolescents with a certain type of blood cancer, T-ALL. Researchers at the Hopp Children’s Cancer Center Heidelberg (KiTZ), the Molecular Medicine Partnership Unit (MMPU) – an inter-institutional partnership between the European Molecular Biology Laboratory (EMBL) and the Medical Faculty of Heidelberg University – and the German Cancer Research Center (DKFZ) were able to show this in a recent study. The results could help to overcome resistance in this form of blood cancer and prevent relapses.

The “Hopp Children’s Cancer Center Heidelberg” (KiTZ) is a joint institution of the German Cancer Research Center (DKFZ), Heidelberg University Hospital (UKHD) and Heidelberg University (Uni HD).

Acute lymphoblastic leukemia (ALL) is the most common form of leukemia in children and adolescents and accounts for a good fifth of all childhood and adolescent cancers. Every year, around 550 to 600 children and adolescents in Germany are diagnosed with this form of blood cancer. Around 80 percent of these can be cured. The others suffer relapses with poor prognoses due to resistance.

Resistance to chemotherapy is particularly common in T-ALL, a subtype of ALL. As a recent study has now shown, the source of the problem is a small treatment-resistant cell population that is already present at the time of diagnosis and multiplies considerably in the event of a relapse.

Researchers from the Molecular Medicine Partnership Unit, the Hopp Children’s Cancer Center Heidelberg (KiTZ) and the German Cancer Research Center (DKFZ) analyzed individual T-ALL cells from a total of 18 patients at the time of diagnosis and after a relapse and compared their molecular make-up with leukemia cells from patients who did not suffer a relapse.

As the single cell analyses showed, many patients carry a small cell population with stem cell-like properties early on in the course of the disease. These stem cell-like cells show particular resistance to chemotherapeutic agents both in cell culture and in mice. The clinical relevance of this discovery was also demonstrated in the analysis of a large number of patient samples: the stem cell-like cells were increasingly found in patients in whom treatment with these chemotherapeutic agents did not work well from the outset. 

Studies in other cancers also indicate that cells with stem cell-like properties are the reason why therapies no longer work. “So far, however, it has not been possible to identify individual stem cell-like T-ALL cells that are responsible for relapses and to precisely characterize their molecular properties,” emphasizes Jan Korbel, head of the “Molecular Pediatric Oncology” research group at MMPU, interim head of EMBL in Heidelberg and research group leader at DKFZ. He heads the MMPU research group and the study together with Andreas Kulozik, Professor of Pediatric Oncology, Hematology and Immunology at the Medical Faculty of Heidelberg University, founder of MMPU, Medical Director of the Clinic for Pediatric Oncology, Hematology and Immunology at UKHD, Director of the Clinical Program of KiTZ and Head of the Clinical Cooperation Unit Pediatric Leukemias at DKFZ.

The single cell analyses also showed that the stem cell-like cancer cells have different molecular characteristics that could also be relevant for therapy decisions: stem cell-like cells with certain gene activity patterns were an indicator of relapse. According to the authors, the stem cell score developed in the study could therefore serve as a clinical biomarker in the future to assess the risk of relapse and, if necessary, adapt the therapy.

“With the approach developed in the study of being able to examine stem cell-like leukemia cells individually and characterize them molecularly, we would also like to examine in future what influence different treatment regimes and therapeutic agents have on the development of these cells,” explains Andreas Kulozik.

The authors hope that stem cell-like cells are a promising therapeutic target for preventing relapses in children and adolescents with T-ALL and overcoming resistance.

Original publication

Costea J. et al. Role of Stem-Like Cells in Chemotherapy Resistance and Relapse in Pediatric T-Cell Acute Lymphoblastic Leukemia. In: Nature Communications (Online publication, June 27, 2025) DOI: 10.1038/s41467-025-61222-1

About the Molecular Medicine Partnership

MMPU is an inter-institutional partnership between the Medical Faculty of Heidelberg University and the European Molecular Biology Laboratory (EMBL).

It promotes innovations and their translational implementation in medicine – at the interface between basic research in molecular biology and clinical healthcare. The MMPU currently consists of nine international and interdisciplinary research groups, which are supported by physicians, doctoral scientists, doctoral students and technicians. The research focus of the MMPU group “Molecular Pediatric Oncology” is on childhood leukemia.

The Hopp Children’s Cancer Center Heidelberg (KiTZ)

The „Hopp Children’s Cancer Center Heidelberg” (KiTZ) is a joint institution of the German Cancer Research Center (DKFZ), Heidelberg University Hospital and Heidelberg University. As the National Center for Tumor Diseases (NCT), which focusses on adult oncology, the KiTZ is based on the US model of so-called “Comprehensive Cancer Centers” (CCC). As a therapy and research center for oncologic and hematologic diseases in children and adolescents, the KiTZ is committed to scientifically exploring the biology of childhood cancer and to closely linking promising research approaches with patient care– from diagnosis to treatment and aftercare. Children suffering from cancer, especially those with no established therapy options, are given an individual therapy plan in the KiTZ, which is created by interdisciplinary expert groups in so-called tumor boards. Many young patients can participate in clinical trials which ensures access to new therapy options. Thus, the KiTZ is a pioneering institution for transferring research knowledge from the laboratory to the clinic.

While the KiTZ focuses on pediatric oncology, the focus of the National Center for Tumor Diseases (NCT), founded in 2004, is adult oncology. Both facilities in Heidelberg are based on the US model of so-called “Comprehensive Cancer Centers” (CCC).

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ’s Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.

To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:

• National Center for Tumor Diseases (NCT, 6 sites)
• German Cancer Consortium (DKTK, 7 sites)
• Hopp Children’s Cancer Center (KiTZ) Heidelberg
• Helmholtz Institute for Translational Oncology (HI-TRON Mainz) – A Helmholtz Institute of the DKFZ
• DKFZ-Hector Cancer Institute at the University Medical Center Mannheim
• National Cancer Prevention Center (jointly with German Cancer Aid)

The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

Heidelberg University Hospital and Faculty of Medicine: Internationally Renowned Patient Care, Research and Teaching

Heidelberg University Hospital (Universitätsklinikum Heidelberg, UKHD) is one of the largest and most prestigious medical centers in Germany. The Medical Faculty of Heidelberg University (Medizinische Fakultät Heidelberg, MFHD) belongs to the internationally renowned biomedical research institutions in Europe. Both institutions have the common goal of developing new therapies and implementing them rapidly for patients. Heidelberg University Hospital and the Medical Faculty of Heidelberg University employs around 14.500 employees and is committed to providing trainings and qualifications. Every year, around 86,000 patients and more than 1.100.000 outpatient cases are treated in more than 50 clinical departments with almost 2.500 beds.

Together with the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and the German Cancer Aid, the UKHD established the first National Center for Tumor Diseases (NCT) in Heidelberg. The goal is to provide care at the highest level as an oncology center of excellence and to rapidly transfer promising approaches from cancer research to the hospital. In addition, the UKHD operates in partnership with the DKFZ and the University of Heidelberg the Hopp Children’s Cancer center Heidelberg (KiTZ), a unique and nationally known therapy and research center for oncological and hematological diseases in children and adolescents.

The Heidelberg Curriculum Medicinale (HeiCuMed) is one of the top medical training programs in Germany. Currently, there are about 4.000 future physicians studying in Heidelberg.

Press contact:

Dr. Alexandra Moosmann
Head of communications KiTZ 
Hopp Children’s Cancer Center Heidelberg (KiTZ) 
Im Neuenheimer Feld 130.3
69120 Heidelberg
T: +49 (0) 6221 56 36434
a.moosmann@kitz-heidelberg.de
presse@kitz-heidelberg.de
www.kitz-heidelberg.de

Dr. Sibylle Kohlstädt
Strategic Communication and Public Relations 
Press speaker 
German Cancer Research Center 
Im Neuenheimer Feld 280
69120 Heidelberg
T: +49 6221 42 2843
F: +49 6221 42 2968
S.Kohlstaedt@dkfz.de
presse@dkfz.de
www.dkfz.de

Julia Bird
Interim Head of Corporate Communications and Press Speaker of Heidelberg University Hospital and Medical Faculty
Im Neuenheimer Feld 672
69120 Heidelberg
T: +49 6221 56-7071
F: +49 6221 56-4544
presse@med.uni-heidelberg.de
www.klinikum.uni-heidelberg.de