Identification of novel therapeutic approaches in a xenograft model of juvenile myelomonocytic leukemia (JMML)

Juvenile myelomonocytic leukemia (JMML) is a highly aggressive myeloproliferative disorder of early childhood and the only curative treatment is hematopoietic stem cell transplantation (HSCT). However, the main cause of treatment failure is relapse in up to 30 % of patients urging the strong need for novel therapies. In JMML, malignant transformation is driven by constitutive activation of the RAS signaling pathway suggesting attractive candidates for therapy. By using our xenograft model that closely mimics human disease, we are testing different novel therapies including BH3-mimetics, RAS pathway inhibitors and HSP90 inhibitors to identify treatment strategies able to cure JMML. It is our primary goal to deplete leukemia-initiating cells to prevent relapse after HSCT. In addition, our studies will contribute to a better understanding of pathogenetic mechanisms of JMML. Eventually, it is our goal to transfer our preclinical observations to phase I/II clinical trials and in that way improve care of JMML patients.

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Artikel online veröffentlicht:
13. Mai 2020