New approach to acute myeloid leukemia therapy

The work focused on certain cancer cells that have a defect in the repair ability of their genetic material. About 15 percent of AML patients are carriers of this genetic variant (called GFI1-36N) and thus usually have a poorer prognosis for the course of the disease. The research team has now found a way to use the defect in the malignant (malignant) cells in therapy. The team was able to demonstrate in cell culture with human leukemia samples that the use of a so-called PARP inhibitor, a drug that blocks a DNA repair pathway, drives these cells to cell death because they can no longer repair defects in the genetic material. The procedure had no significant effect on the non-malignant cells.

Retrospective analysis of a study group of AML patients who received a PARP inhibitor showed that 80 percent of all patients with this variant responded to the therapy. This promising result now needs to be confirmed in a controlled trial. Acute leukemias are a form of blood cancer that are usually fatal within weeks without treatment. Until now, treatment has consisted of chemotherapy, often followed by stem cell transplantation. 

Cyrus Khandanpour and Nikolas von Bubnoff, Clinic for Hematology and Oncology, Lübeck Campus, Hauke Busch, Institute for Experimental Dermatology, Lübeck Campus, and Friedrich Stölzel, Clinic for Internal Medicine II, Kiel Campus, are the lead investigators. The study was supported, among others, by the German Cancer Aid and published in the renowned journal Blood. The study was conducted in cooperation with Matthias Mann, Max Planck Institute of Biochemistry, Ashok Kumar Jayavelu, Hopp Children's Cancer Center Heidelberg (KiTZ) and German Cancer Research Center (DKFZ), as well as several university hospitals (Hannover, Dresden, Münster, Essen) and research institutions in New York, USA, and Montreal, Canada. Also involved at the Lübeck campus were Pradeep Patnana (Khandanpour's research group) and Axel Künstner (Institute of Experimental Dermatology). 
 

Original publication

Daria Frank et al., Germline variant GFI1-36N affects DNA repair and sensitizes AML cells to DNA damage and repair therapy. Blood, Sep 26, 2023. https://doi.org/10.1182/blood.2022015752
 

Source: University Hospital Schleswig-Holstein