The MDS Beacon™

Dr. Pearlie Epling-Burnette, from the H. Lee Moffitt Cancer Center & Research Institute, presented new research highlighting immune system disorders at the 10th Annual International Symposium for Myelodysplastic Syndromes (MDS) in Patras, Greece. Auto-immune diseases seem to affect some MDS patients, even though it is only a small percentage of the overall MDS patient population.

Her presentation on May 7, called “Controlling the ‘Fate’ of T-Cells in MDS,” focused on natural killer T-cells, white blood cells that are the immune system’s first non-specific defense against foreign pathogens and defective cells. Natural killer cells are normally functional in low-risk MDS patients, but they may become exhausted with time and lose their ability to suppress cancer cells. As a result, numbers of abnormal leukemic cells may increase, allowing MDS to progress to Acute Myeloid Leukemia (AML). Her talk highlighted research about why T-cells lose their ability to suppress cancer cells, and increasing evidence that receptors that activate them may play a role in their fate. The immune system seems to be linked to MDS through this research, as reduced natural killer function is associated with higher-risk MDS.

Dr. Burnette’s team is also exploring other aspects of immunology that are important in MDS, such as specific gene sequences that have been found to be linked to patient responses to treatments. Corresponding gene markers are being developed to predict responses and possible underlying autoimmune disorders. Such markers can become an important part of distinguishing MDS from other possible diseases and ensuring that patients receive the most appropriate therapy as soon as possible. Studies have shown that MDS patients with autoimmune diagnoses have better responses to immunosuppressive drugs than only MDS-specific therapies. To date, the National Heart Blood and Lung Institute (NHLBI) at the National Institutes of Health (NIH) has shown that younger patients with lower-risk MDS and the HLA-DR15 gene sequence (genotype) respond most favorably to immunosuppressive drugs.

Patients who need to address compound autoimmune-MDS disorders will benefit from establishment of gene biomarkers. Identification of genotypes, such as HLA-DR15, can increase the rate of successful MDS treatments by specifying patients who will have good responses to immunosuppressive therapy.

“If these markers are confirmed to be predictive for response to immunosuppressive therapy in an independent study, then patients with the biomarkers will be placed on immunosuppressive drugs as a first line of therapy,” says Epling-Burnette.

As research in immunopathology clarifies the relationship between autoimmune disorders and MDS, combination therapies can become more individualized.
“We are working on better predictive biomarkers to indicate which patients have autoimmunity so that immunosuppressive therapy can be given to the right patient,” says Epling-Burnette. “Since the currently available immunosuppressive therapies work non-specifically, we hope to develop novel treatment modalities based on specific immune abnormalities in MDS.”

A video of her interview following her presentation can be viewed at the MDS Foundation International Symposium Web site.