Acute myeloid leukemia (AML) is a cancer of the hematopoietic cells that causes the uncontrolled proliferation of certain immature blood cells. The disease is characterized by frequent relapses driven by leukemic stem cells (LSCs) or progenitor cells.
The treatment of AML usually involves intensive chemotherapy to normalize the blood count and remove diseased cells from the bone marrow. However, due to the toxic side effects, this approach is unsuitable for patients with weakened immune systems. A more targeted therapy might result in improved patient outcomes and fewer side effects.
In their current publication in Science Translational Medicine, Sayantanee Dutta, Philipp Jost, Michael Dengler, and their team present an innovative and promising therapeutic approach that could facilitate precise and selective treatment of AML in the future.[1]
Focus on stem cells
Leukemic stem cells are a major problem in the treatment of AML. These dormant cells possess highly efficient DNA repair mechanisms and a distinctive ability to expel drugs selectively. They are more resistant than conventional therapies. Consequently, these leukemic stem cells play a key role in disease persistence and recurrence, i.e., the return of the cancer. Selective elimination of these cells might be especially advantageous for patients.
Through extensive investigations of primary samples from AML patients and various AML mouse models, Philipp Jost’s team demonstrated that the body’s own cytokine, lymphotoxin alpha, has an AML-inhibiting effect and thus therapeutic potential to eliminate malignant leukemic stem cells specifically. Lymphotoxin alpha employs an intracellular mechanism and offers clear advantages compared with conventional cytotoxic therapies. The researchers showed that, in contrast to aggressive chemotherapy, which is frequently accompanied by bone marrow suppression, lymphotoxin alpha can inhibit cancer cells while promoting healthy blood cells.
The findings show the clear therapeutic potential of lymphotoxin alpha, which might fundamentally change how AML is treated. In particular, older or weakened patients who are unable to receive chemotherapy might benefit from this new approach.
Reference
[1] Höckendorf U, Dutta S, Kloos A, Runtsch M, Zötsch C, Vosberg S, Wang Y, Kienreich S, Flasch B, Malovan G, Jäger V, Stanzer S, Prein S, Odinius TO, Wagner CV, Buschhorn L, Dill V, Perfler B, Haferlach T, Döhner K, Götze KS, Ruland J, Bassermann F, Wahida A, Heikenwälder M, Branca C, Schmöllerl J, Zuber J, Burk AC, Zeiser R, Sill H, Jayavelu AK, Zebisch A, Heuser M, Dengler MA, Jost PJ. Lymphotoxin alpha eradicates acute myeloid leukemia and simultaneously promotes healthy hematopoiesis in mice. Sci Transl Med. 2025 Nov 26;17(826):eadu3313. doi: 10.1126/scitranslmed.adu3313. Epub 2025 Nov 26. PMID: 41296826.
Featured image: The researchers: MedUni Graz, Team Univ. Prof. Dr. Philipp J. Jost. Pgot courtesy: © 2025 Med Uni Graz/Lunghammer
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