Study identifies possible new acute leukemia marker, treatment target

May 13, 2013

A study has identified microRNA-155 as a new independent prognostic marker and treatment target in patients with acute myeloid leukemia that has normal-looking chromosomes under the microscope (that is, cytogenetically normal acute myeloid leukemia, or CN-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 CN-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 in CN-AML development, and that it could be a valuable target for the emerging class of drugs designed to inhibit microRNAs, says first author Dr. Guido Marcucci, professor of , a leukemia specialist and associate director for Translational Research at the OSUCCC – James. "MiR-155 would be relatively easy to measure at the time of diagnosis," Marcucci says. "We believe it will prove to be a good marker for stratifying patients according to and a good target for emerging compounds designed to inhibit microRNAs."

Principal investigator Dr. Clara D. Bloomfield, Distinguished University Professor and Ohio State University Cancer Scholar and Senior Advisor and William Greenville Pace III Endowed Chair in notes that, "Overall, our findings indicate that miR-155 expression is a strong and independent in CN-AML, and they provide 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.

For this study, Marcucci, Bloomfield and their colleagues analyzed bone-marrow or blood specimens from 363 CN-AML patients, 153 of whom 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.

The study's key technical findings include:

  • Overall, patients with high miR-155 expression were about 50 percent less likely to achieve complete remission, and to have a 60 percent increase in the risk of death compared to patients with low miR-155 expression.
  • High miR-155 expression was associated with pro-survival, proliferation 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 biological differences.

Explore further: Researchers say one specific microrna promotes tumor growth and cancer spread

Related Stories

Researchers say one specific microrna promotes tumor growth and cancer spread

April 3, 2013
Researchers at Moffitt Cancer Center have determined that the overexpression of microRNA-155 (miR-155), a short, single strand of ribonucleic acid encoded by the miR-155 host gene, promotes the growth of blood vessels in ...

A microRNA prognostic marker identified in acute leukemia

May 14, 2012
A study has identified microRNA-3151 as a new independent prognostic marker in certain patients with acute leukemia. The study involves patients with acute myeloid leukemia and normal-looking chromosomes (CN-AML).

Mini-molecule governs severity of acute graft vs. host disease, study finds

March 12, 2012
Researchers have identified a molecule that helps control the severity of graft-versus-host disease, a life-threatening complication for many leukemia patients who receive a bone-marrow transplant.

Gene mutation signals a high risk of recurrence in some older acute-leukemia patients

December 12, 2011
Older people with acute myeloid leukemia and normal looking chromosomes in their cancer cells have a higher risk of recurrence if they have mutations in a gene called ASXL1, according to a new study by researchers at the ...

Atherosclerosis: Specific microRNAs promote inflammation

March 22, 2013
(Medical Xpress)—Atherosclerosis, an inflammatory reaction, is at the root of the most common forms of cardiovascular disease. Researchers at Ludwig-Maximilians-Universitaet in Munich have now identified a microRNA that ...

Recommended for you

No dye: Cancer patients' gray hair darkened on immune drugs

July 21, 2017
Cancer patients' gray hair unexpectedly turned youthfully dark while taking novel drugs, and it has doctors scratching their heads.

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.