Identification of two cancer genes for targeted leukemia therapy
Modern cancer therapy aims to tailor treatment to each individual patient's needs by identifying specific molecular targets with essential functions in the tumor of these patients. Leukemia, or blood cancer, is a common tumor in children and occurs in many different genetic variations, thus complicating treatment. In a recent study, researchers around Irmela Jeremias, Head of the Research Unit “Apoptosis in Hematopoietic Stem Cells” (AHS) at Helmholtz Munich, identified two genes that can be effectively used in precision medicine of acute myeloid leukemia.
Which genetic alterations represent powerful anchors for targeted leukemia therapy? First authors Maryam Ghalandary and Yuyiao Gao from the Research Unit AHS headed by Irmela Jeremias have addressed this question in their recent work published in the journal Blood. Methodically, the researchers worked with patient-derived xenograft (PDX) mouse models, which allow studying tumor cells of individual patients while growing in mice and faithfully mimicking the clinical situation in the individual patient. After transplanting tumor cells in mice, the researchers systematically knocked out several genes with so-called “gene scissors” to assess their function in the tumor.
"We could show for the first time that the genes WT1 or DNMT3A harbor an essential function in leukemia stem cells of individual patients, although the literature did not suggest it," state Maryam Ghalandary and Yuyiao Gao. "WT1 and DNMT3A can be used as targets for leukemia therapy in certain patients to eliminate their tumor cells via precision oncology."
The study impressively demonstrates the importance of using such in vivo models, since the results of the mouse model could not be reproduced in cell culture dishes.
Ghalandary et al. (2022). WT1 and DNMT3A play essential roles in the growth of certain patient AML cells in mice. Blood, blood.2022016411. Advance online publication. https://doi.org/10.1182/blood.2022016411
Prof. Irmela Jeremias, Head of the “Research Unit Apoptosis in Hematopoietic Stem Cells” at Helmholtz Munich, Contact: Irmela.Jeremias@helmholtz-muenchen.de
This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Consolidator Grant and Starting Grant agreement No. 681524 and No. 950293 to I.J. and M.M., respectively); a Mildred Scheel Professorship by German Cancer Aid; Bettina Bräu Stiftung and Dr. Helmut Legerlotz Stiftung (to I.J.) and a China Scholarship Council (to Y.G;. CSC No. 202108080142).