The most frequent type of malignancy in kids is acute lymphoblastic leukemia (ALL). The condition of T-lineage ALL, a kind of leukemia that develops from initial T lineage cells, is worse than that of B-lineage ALL. Relapsed T-ALL has an extremely poor prognosis, necessitating the urgent need for novel treatments.
A new medicine combination that is beneficial against T-ALL was identified through a collaboration between Tampere University’s Faculty of Medicine and Health Technology and Harvard Stem Cell Institute.
The findings are based on an earlier study by a research team at Tampere University, which showed that dasatinib, a generic tyrosine kinase inhibitor, was successful in about one-third of the patient samples studied. The current study looked for pharmacological combinations that might have an improved synergistic effect with dasatinib because the efficacy of a single agent in the treatment of leukemia often declines quickly.
Temsirolimus, a medication that blocks a parallel signaling pathway, was an example of this. In comparison to utilizing a single agent, the two medicines worked better together to eradicate leukemia cells in cell culture, zebrafish, and mouse models.
During the study, a new drug screening method for the rapid assessment of drug responses in leukemia samples was developed and optimized in a zebrafish T-ALL model. In this screen, an effective drug combination was found, which was later confirmed by several cell line models, patient samples and mouse models.”
Saara Laukkanen PhD, Study First Author, Tampere University
“This has been a long project, taking 4–5 years, and as a result, we now understand the mechanism of action of these drugs at molecular level in T-ALL,” Laukkanen adds.
Laukkanen worked with Professor David Langenau’s research team on the study for six months while serving as a visiting researcher at the Harvard Stem Cell Institute in Boston.
This is a promising new treatment option for T-acute leukemia. The next step is to take the discovery into clinical practice for patients with relapsed or refractory disease via early phase clinical trials.”
Olli Lohi MD, PhD, Research Director, Tampere University
Lohi was also a research director at Tays Hospital’s Cancer Centre.
“The development of precision treatments is slow and requires accurate knowledge of the molecular mechanisms that cause and maintain disease. Here we utilized a specific dependency of T-ALL cells on certain signaling routes that the combination of dasatinib and temsirolimus shuts off,” Lohi says.
Blood, the most esteemed academic publication in the discipline of hematology, published the findings. Scientists from the Universities of North Carolina, Eastern Finland, and Helsinki, in contrast to those from Tampere University and the Harvard Stem Cell Institute, also participated in the research.
Laukkanen, S., et al. (2022) Combination therapies to inhibit LCK tyrosine kinase and mTOR signaling in T-cell Acute Lymphoblastic Leukemia. Blood. doi.org/10.1182/blood.2021015106.