Featured Research

from universities, journals, and other organizations

AML score combining genetic, epigenetic changes might help guide therapy

Date:
January 8, 2014
Source:
Ohio State University Wexner Medical Center
Summary:
Currently, doctors use chromosome markers and gene mutations to determine the best treatment for patients with acute myeloid leukemia. But a new study suggests that a score based on seven mutated genes and the epigenetic changes that the researchers discovered were also present might help guide treatment by identifying novel subsets of patients. Patients with a low score had the best outcomes, and those with high scores had the poorest outcomes.

Currently, doctors use chromosome markers and gene mutations to determine the best treatment for a patient with acute myeloid leukemia (AML). But a new study suggests that a score based on seven mutated genes and the epigenetic changes that the researchers discovered were present might help guide treatment by identifying novel subsets of patients.

Related Articles


The findings, published in the Journal of Clinical Oncology, come from a study 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 epigenetic change used in the study is DNA methylation. It involves the addition of methyl groups to DNA, which can reduce or silence a gene's activity, or expression. Abnormal DNA methylation alters normal gene expression and often plays an important role in cancer development.

Overall, the findings suggest that patients with a low score -- indicating that one or none of the seven genes is overexpressed in AML cells -- had the best outcomes, and that patients with high scores -- that is, with six or seven genes highly expressed -- had the poorest outcomes.

"To date, disease classification and prognostication for AML patients have been based largely on chromosomal and genetic markers," says principal investigator Clara D. Bloomfield, MD, Distinguished University Professor, Ohio State University Cancer Scholar and Senior Adviser.

"Epigenetic changes that affect gene expression have not been considered. Here we show that epigenetic changes in previously recognized and prognostically important mutated genes can identify novel patient subgroups, which might better help guide therapy," says Bloomfield, who is also the William Greenville Pace III Endowed Chair in Cancer Research at Ohio State.

The seven-gene panel was identified in 134 patients aged 60 and older with cytogenetically normal acute myeloid leukemia (CN-AML) who had been treated on Cancer and Leukemia Group B (CALGB)/Alliance clinical trials.

The researchers computed a score based on the number of genes in the panel that were highly expressed in patients' AML cells, and retrospectively tested the score in two groups of older patients (age 60 and up) and two groups of younger patients (age 59 and under).

Patients with a low score -- indicating that one or none of the seven genes is overexpressed -- had the best outcomes. Patients with high scores -- that is, with six or seven genes highly expressed -- had the poorest outcomes.

"For this seven-gene panel, the fewer highly expressed genes, the better the outcome," says first author Guido Marcucci, MD, professor of medicine and the associate director for translational research at the OSUCCC -- James. "In both younger and older patients, those who had no highly expressed genes, or had one highly expressed gene had the best outcomes."

Most adults with AML are not cured by current therapies. Only about 40 percent of patients younger than age 60 and about 10 percent of patients 60 and older are alive after three years, so new strategies for treating the disease and for matching the right patient with the right treatment are needed, Bloomfield says.

For this study, Bloomfield, Marcucci and their colleagues used next-generation sequencing to analyze regions of methylated DNA associated with prognostically important gene mutations in CN-AML cells from 134 patients aged 60 and older.

The seven genes identified by the researchers were CD34, RHOC, SCRN1, F2RL1, FAM92A1, MIR155HG and VWA8. For each of these genes, lower expression and higher DNA methylation were associated with better outcome. A summary score was developed based on the number of genes in the panel showing high expression. The researchers validated the score in four sets of patients: older and younger patients with primary AML, and older and younger patients with CN-AML (355 patients total).

When Bloomfield, Marcucci and their collaborators applied the unweighted score to the initial training set of 134 older patients, those with one or no highly expressed genes had a 96 percent complete-remission rate, 32 percent three-year disease-free survival rate and 39 percent three-year overall survival.

Patients with six-to-seven highly expressed genes, on the other hand, had a 25 percent complete-remission rate, a 0 percent three-year disease-free survival rate and 4 percent three-year overall survival.

For younger adult patients, those under age 60, those with one or no highly expressed genes had a 91-100 percent complete-remission rate, a 60-65 percent three-year disease-free survival rate, and a 76-82 percent three-year overall survival. Patients with six-to-seven highly expressed genes, on the other hand, had a 53-71 percent complete-remission rate, a 13-17 percent three-year disease-free survival rate and a 7-24 percent three-year overall survival.

"Overall, our findings suggest that the unweighted-summary score is a better model compared with all other prognostic markers and previously reported gene-expression profiles," Bloomfield says.


Story Source:

The above story is based on materials provided by Ohio State University Wexner Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. G. Marcucci, P. Yan, K. Maharry, D. Frankhouser, D. Nicolet, K. H. Metzeler, J. Kohlschmidt, K. Mrozek, Y.-Z. Wu, D. Bucci, J. P. Curfman, S. P. Whitman, A.-K. Eisfeld, J. H. Mendler, S. Schwind, H. Becker, C. Bar, A. J. Carroll, M. R. Baer, M. Wetzler, T. H. Carter, B. L. Powell, J. E. Kolitz, J. C. Byrd, C. Plass, R. Garzon, M. A. Caligiuri, R. M. Stone, S. Volinia, R. Bundschuh, C. D. Bloomfield. Epigenetics Meets Genetics in Acute Myeloid Leukemia: Clinical Impact of a Novel Seven-Gene Score. Journal of Clinical Oncology, 2013; DOI: 10.1200/JCO.2013.50.6337

Cite This Page:

Ohio State University Wexner Medical Center. "AML score combining genetic, epigenetic changes might help guide therapy." ScienceDaily. ScienceDaily, 8 January 2014. <www.sciencedaily.com/releases/2014/01/140108123716.htm>.
Ohio State University Wexner Medical Center. (2014, January 8). AML score combining genetic, epigenetic changes might help guide therapy. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2014/01/140108123716.htm
Ohio State University Wexner Medical Center. "AML score combining genetic, epigenetic changes might help guide therapy." ScienceDaily. www.sciencedaily.com/releases/2014/01/140108123716.htm (accessed December 19, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, December 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins