A protein-sugar molecule, CD99, occurs more frequently than normal on come cells responsible for blood cancers, including acute myeloid leukemia (AML) and the related myelodysplastic syndromes (MDS).
This is the finding of a study (“CD99 is a therapeutic focus on disease stem cells in myeloid malignancies”) led by researchers from NYU Langone Medical Center and Memorial service Sloan Kettering Cancer Center, and published online in Science Translational Medicine .
Building on this discovery, the study authors designed an antibody that recognizes and destroys CD99-covered leukemia cells whilst sparing normal blood stem cells, a finding verified by experiments in human cells and in mice along with AML cells.
“Our findings not just identify a new molecule expressed on stem cells that will drive these human malignancies, but we show that will antibodies against this target can directly kill human AML stem cells, ” says corresponding study author, Captain christopher Y. Park, MD, PhD, associate professor in the Division of Pathology at NYU Langone and its Perlmutter Malignancy Center. “While we still have important details to exercise, CD99 is likely to be an exploitable therapeutic target for most AML and MDS patients, and we are working urgently to complete a therapy for human testing. ”
AML and MDS arise from abnormal stem tissues that build up in bone marrow until they hinder normal blood cell production. Patients struggle with anemia, improved risk for infection, and bleeding.
The study results are based on the understanding that cancers, like normal cells, contain stem cells that give rise to all the other tissue. Such “cancer stem cells” are known to be major motorists of many cancer types. In AML, a small group of leukemic stem cells become incapable of maturing into red or white bloodstream cells as intended. Most leukemias respond initially in order to standard treatment, but relapse is common as standard remedies fail to kill leukemia stem cells, which continue to grow.
The research team became interested in CD99 when they observed that it occurs frequently on AML plus MDS cells, and then noted in the literature that CD99 is elevated in a rare bone cancer called Ewing’s Sarcoma. This prompted them to see if CD99 was essential in the development of these blood diseases.
When researchers examined stem cell populations from seventy nine AML and 24 MDS patients, they found that will approximately 85 percent of stem cells in both groupings expressed high levels of CD99. The levels were so higher that diseased stem cells could be cleanly separated through related, normal stem cells in AML patients.
Upon confirming that CD99 was plentiful on leukemia stem cells, the research team then produced several CD99 antibodies, and chose to focus on the one that the majority of effectively killed those cells. Researchers found that when the research antibody attaches itself to CD99 on the surface of a malignancy stem cell, it sends a signal inside the cell that will increases the activity of enzymes called SRC-family kinases.
While the team does not yet know why, the particular binding of their antibody to CD99, and the subsequent service of these enzymes, causes leukemia stem cells to expire. Most cells with genetic mistakes leading to cancer “sense” they are flawed and self-destruct, but CD99, so the concept goes, may be part of a mechanism that prevents this particular. As the antibody binds to CD99, it appears to unnecessary this block on self-destruction.
“With the appropriate support, we believe we can rapidly determine the very best antibodies for use in patients, produce them at the quality necessary to verify our results, and apply for permission to begin medical trials, ” says Dr . Park.