Possible new acute leukemia marker treatment target identified
MicroRNA-155 has been identified as a new independent prognostic marker and treatment target in patients with acute myeloid leukemia whose chromosomes look normal under the microscope. When microRNA-155 is present at abnormally high levels in this type of leukemia, known as cytogenetically normal acute myeloid leukemia (CN-AML), patients are less likely to have a complete remission. Also, both disease-free periods and overall survival are shorter. The effect is independent of other known prognostic gene mutations present in the cells.
These findings suggest that miR-155 plays a pivotal role in CN-AML development. Also, miR-155 could be a valuable target for an emerging class of drugs designed to inhibit microRNAs.
“MiR-155 would be relatively easy to measure at the time of diagnosis,” said Guido Marcucci, MD, of The Ohio State University in Columbus. “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.”
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.
“Overall, our findings indicate that miR-155 expression is a strong and independent prognostic marker in CN-AML, and they provide clinical validation of data from preclinical models that support a crucial role of miR-155 in leukemia,” said principal investigator Clara D. Bloomfield, MD, also of Ohio State.
This study analyzed bone-marrow or blood specimens from 363 CN-AML patients, with 153 under age 60 years and 210 age 60 years and over. This study was published in the Journal of Clinical Oncology (2013; doi: 10.1200/JCO.2012.45.6228).
The study found that patients with high miR-155 expression were about 50% less likely to achieve complete remission and had a 60% increase in the risk of death compared with patients with low miR-155 expression. High expression of miR-155 was associated with pro-survival, proliferation, and inflammatory gene activity, which suggests a pivotal role in leukemia development.In patients under 60 years of age, higher miR-155 expression was associated with a lower complete response rate, shorter disease-free survival, and shorter overall survival. In patients age 60 years and older, higher miR-155 expression was associated only with a lower complete response rate and shorter overall survival. The differences 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 biological differences.