Key Mechanism And Potential Target To Prevent Leukemia Identified

Key Mechanism And Potential Target To Prevent Leukemia Identified
(Image source)
Researchers have identified two proteins that appear crucial to the development, and patient relapse, of acute myeloid leukemia. They have also shown they can block the development of leukemia by targeting those proteins. The studies, in animal models, could lead to new effective treatments for leukemias that are resistant to chemotherapy. The research was reported today in the journal Cell Reports.
Mutations in two cellular structures known as receptors have previously been identified as cancer-causing. Patients with those mutations generally have a poor prognosis, but scientists have been uncertain what mechanism led to leukemia in the stem cells with those mutations. In the Cell Reports paper, the researchers describe the mechanism that leads to the development of acute myeloid leukemia, identifying two proteins known as FAK and PAK1 as key to the process.
In experiments with mice, the researchers showed that eliminating, or "knocking out," the genes that produce FAK and PAK1 prevented the development of leukemia in mice, even though their bone marrow stem cells contained the cancer-causing receptor mutations. Eliminating the FAK and PAK1 proteins did not prevent the mice from otherwise producing and maintaining a normal blood system, the researchers said.
In additional experiments in mice and human cell tissue samples, the researchers identified several drug compounds that target FAK and PAK1, now available for experimental use but not approved for use in humans, that were just as effective in blocking development of leukemia as knocking out the FAK and PAK1 genes.
The next step is to continue testing and refining those experimental drug compounds to verify their effectiveness for potential testing in human trials.