Hematologic Malignancies Marker Unmasked

Study Identifies Possible Acute Leukemia Marker and Treatment Target

Guido MarcucciA study led by researchers at the OSUCCC – James has identified microRNA-155 as an independent prognostic marker and treatment target in patients with acute myeloid leukemia (AML) that has normal-looking chromosomes (i.e., cytogenetically normal AML, or CN-AML).

The study found that, when microRNA-155 (miR-155) is present at abnormally high levels in CNAML 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.

The findings suggest that miR- 155 plays a pivotal role in CN-AML development and could be a target for emerging drugs designed to inhibit microRNAs, says first author Guido Marcucci, MD, a leukemia specialist and associate director for translational research at the OSUCCC – James.

“MiR-155 would be relatively easy to measure at diagnosis,” Marcucci says. “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.

“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,” says principal investigator Clara D. Bloomfield, MD, a Distinguished University Professor who serves as cancer scholar and senior adviser to the OSUCCC – James.

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.

Published in the Journal of Clinical Oncology with an accompanying editorial and an “Understanding the Pathway” article.

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