Researchers from UT Southwestern have recently identified receptors crucial for the development of acute myeloid leukemia (AML), the most frequent acute leukemia affecting adults.
The study entitled “The ITIM-containing receptor LAIR1 is essential for acute myeloid leukemia development” was published in Nature Cell Biology by Xunlei Kang, first author, and Cheng Cheng Zhang, senior author, from the Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center in Dallas, along with colleagues. In this study, the research team revealed that a type of class of receptors containing the immunoreceptor tyrosine-based inhibition motif (ITIM), which inhibits immune responses, are central to the development of AML.
Acute myeloid leukemia (AML) is a type of blood and bone marrow tumor where some stem cells or progenitor cells do not develop properly into mature forms of white blood cells and turn into atypical red cells, called leukemia cells, which proliferate in the bone marrow and blood taking the place of healthy white blood cells, red blood cells, and platelets. This in turn leads to infections, anemia, or bleeding. These cells can multiply in other parts of the body, including the central nervous system, skin, and gums. In adult patients with AML the most frequent symptoms are fever, tiredness, and easy bruising or bleeding.
Importantly, standard therapies do not show significant success in leukemia cases, normally even under constant therapy, the majority of AML patients relapse within 5 years, according to published studies.
“We showed that these receptors are expressed by AML cells and that they support the development of AML. Although counterintuitive, this result is consistent with the generally immune-suppressive and thus tumor-promoting roles of inhibitory receptors in the immune system,” said Dr. Zhang in a news release. Dr. Zhang added that these results suggest that blocking ITIM-receptor signaling together with standard treatments may constitute a new approach for AML therapy.
This study was focused on an ITIM-containing receptor designated LAIR1. The research team found that removing LAIR1 blocked the development of the disease in different mouse models of leukemia. They also identified a relevant pathway that enables the survival and self-renewal of AML cells, the mechanism by which LAIR1 promotes AML development.
Dr. Zhang said that their findings may explain why standard therapies may not target efficiently cancer stem cells because these inhibitory receptors allow leukemia stem cells to survive to standard treatments, ultimately leading to tumor relapse. He added that blocking ITIM-receptor signaling may be a potential new and effective approach to target leukemia stem cells and lead to total remission of the malignancy.
Dr. Zhang highlighted that there is an urgent need for novel therapies to treat AML, since new treatments have not been approved in the last 30 years. Although there are 50 experimental drugs under clinical trials until now very few drugs have showed promising results.
These findings may contribute for the identification of signaling pathways pivotal to the activity of leukemia stem cells providing targets for the development of novel treatments.