Cancer Research Lab

The expression of microRNAs in acute myeloid leukemia (AML) is closely associated with disease prognosis and cytogenetics, according to a study by American and Italian researchers published online in the January 10th issue of Blood. The study also found that a small subset of microRNAs (miRNAs) correlates with AML survival.

MiRNAs are small (19-25 nucleotides long), non-coding RNAs that down-regulate gene expression. Their expression has been linked over the past 5 years or so to hematopoiesis and to cancer in both humans and mice.

The first report associating miRNAs and cancer involved chronic lymphocytic leukemia. Because of the specific mechanisms causing AML, and because patients with AML often have a relatively poor prognosis, creating a need for novel therapies, the researchers attempted to determine whether miRNAs are associated with cytogenetic abnormalities and clinical features in AML.

Dr. Ramiro Garzon of Ohio State University in Columbus and colleagues obtained bone marrow and blood samples from 182 untreated patients newly diagnosed with AML. Using a microarray system, the researchers analyzed the miRNA expression in 122 of these AML samples; the other 60 pretreatment samples were used to validate the miRNA signatures with quantitative real-time PCR. (A second cohort of 54 patients with relapsed or refractory AML was also evaluated.)

The researchers found a “distinct spectrum” of miRNA expression in the AML patients versus normal CD34+ progenitor cells, identifying 26 down-regulated miRNAs and none that were up-regulated. PCR testing of seven miRNAs validated all but one.

“Similar miRNAs signatures to those of the untreated patients were obtained” from the relapsed/refractory AML patients, the researchers wrote, “thereby supporting the hypothesis that miRNA expression is largely driven by cytogenetics.”