Study Identifies Possible New Treatment Target for Acute Leukemia
A study has identified microRNA-155 as a new independent prognostic marker and treatment target in patients with cytogenetically normal acute myeloid leukemia (AML).
The study was led by researchers at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James). The researchers found that when microRNA-155 (miR-155) is present at abnormally high levels in cytogenetically normal AML cells, patients are less likely to have a complete remission, and they experience a shorter disease-free period and shorter overall survival. The effect is independent of other known prognostic gene mutations present in the cells.
Published in the Journal of Clinical Oncology with an accompanying editorial and an “Understanding the Pathway” article, the findings suggest that miR-155 plays a pivotal role in cytogenetically normal AML development, and that it could be a valuable target for the emerging class of drugs designed to inhibit microRNAs, said first author Guido Marcucci, MD, Professor of Hematology and Associate Director for Translational Research at the OSUCCC – James.
microRNA-155
“MiR-155 would be relatively easy to measure at the time of diagnosis,” Dr. Marcucci said. “We believe it will prove to be a good marker for stratifying patients according to recurrence risk and a good target for emerging compounds designed to inhibit microRNAs.”
Principal investigator Clara D. Bloomfield, MD, Distinguished University Professor and Ohio State University Cancer Scholar and Senior Advisor and William Greenville Pace III Endowed Chair in Cancer Research noted that, “Overall, our findings indicate that miR-155 expression is a strong and independent prognostic marker in cytogenetically normal AML, and they provide clinical validation of data from preclinical models that support a crucial role of miR-155 in leukemia.”
The researchers also note that because a molecule called NF-kB is believed to regulate miR-155, treatments that inhibit that molecule might also help patients with high miR-155 levels.
Cells use microRNA molecules to help regulate the kinds and amount of proteins they make. Abnormal levels of certain microRNAs are likely to play a key role in cancer development. Abnormally high expression of miR-155 is associated with lymphoma, aggressive chronic leukemias, and certain solid tumors, and microRNA levels have been associated with patient survival.
Study Details
For this study, Drs. Marcucci, Bloomfield, and their colleagues analyzed bone marrow or blood specimens from 363 patients with cytogenetically normal AML. Of these patients, 153 were under age 60 and 210 were age 60 and over. All were treated on Cancer and Leukemia Group B (CALGB) clinical trials.
The researchers evaluated the association of abnormal miR-155 expression levels with clinical and molecular characteristics and with disease-free survival and overall survival.
Key Findings
Overall, patients with high miR-155 expression were about 50% less likely to achieve complete remission, and experienced a 60% increase in the risk of death compared to patients with low miR-155 expression.
High miR-155 expression was associated with survival and proliferation of leukemia cells and inflammatory gene activity, suggesting a pivotal role in leukemia development.
In patients under age 60, higher miR-155 expression was associated with a lower complete response rate, and shorter disease-free survival and overall survival; in older patients, higher miR-155 expression was associated only with a lower complete response rate and shorter overall survival.
The difference between older and younger patients may be related to differences in the intensity of consolidation therapy administered to younger versus older patients, as well as to biologic differences.
Funding from the NIH/National Cancer Institute (grants CA101140, CA114725, CA31946, CA33601, CA16058, CA77658, CA129657 and CA140158), The Coleman Leukemia Research Foundation, the Deutsche Krebshilfe-Dr Mildred Scheel Cancer Foundation, the Pelotonia Fellowship Program, and the Conquer Cancer Foundation supported this research.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
