Navigation Links
Inherited DNA change explains overactive leukemia gene

  • An overactive BAALC gene in acute leukemia cells identifies patients whose disease is likely to respond poorly to standard therapy.
  • This study discovered why the gene is often overactive.
  • The findings may provide a prognostic marker that can help guide therapy in these patients.

COLUMBUS, Ohio A small inherited change in DNA is largely responsible for overactivating a gene linked to poor treatment response in people with acute leukemia.

The study by researchers at the Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James) focused on a gene called BAALC. This gene is often overactive, or overexpressed, in people with acute myeloid or acute lymphoblastic leukemia, and it indicates that the disease is likely to respond poorly to standard therapy.

This study discovered that BAALC overexpression is caused by a small change called a single nucleotide polymorphism, or SNP (pronounced "snip") in the gene's DNA. The SNP alters the gene's "On" switch, allowing a different molecule to keep it "running" when it shouldn't.

"We want to emphasize," says principal investigator Dr. Albert de la Chapelle, professor of medicine, the Leonard J. Immke Jr. and Charlotte L. Immke Chair in Cancer Research, and co-leader of the Molecular Biology and Cancer Genetics Program, "that this SNP does not raise an individual's risk of developing leukemia, but it does predispose to overexpression of the BAALC gene, which is associated with leukemia development and poor response to treatment."

The findings, published recently in the Proceedings of the National Academy of Sciences, suggest that this SNP could be a useful marker of prognosis and for guiding therapy in acute leukemia patients.

Specifically, the DNA change caused by the SNP creates a binding site for an activating molecule called RUNX1, which is also involved in the formation of normal and malignant blood cells. The researchers showed that patients with high levels of RUNX1 protein also had high levels of BAALC gene expression, while those with low RUNX1 protein had low BAALC gene expression.

For this study, de la Chapelle and his colleagues used DNA sequencing to examine the genomic region of BAALC in 253 patients with cytogentically normal AML (CN-AML) treated in Cancer and Leukemia Group B clinical trials. The analysis revealed nine SNPs of interest, but the researchers focused only on one called rs62527607[T] which creates a RUNX1 binding site in the BAALC promoter region.

The researchers validated the findings in 105 CN-AML patients enrolled in the German-Austrian AML Study Group trials for adult patients. The validation group findings supported the association of high BAALC expression with the SNP, and high RUNX1 expression with high BAALC expression.

"We doubt that this SNP is entirely responsible for BAALC overexpression, but we do believe it is a major contributor to the overactivity," de la Chapelle says.

Contact: Darrell E. Ward
Ohio State University Medical Center

Related medicine news :

1. Family Tree May Aid Treatment of Inherited Heart Disorders
2. How mitochondrial DNA defects cause inherited deafness
3. Study Finds Gene Behind Inherited Cases of Enlarged Heart
4. Scientists Identify Inherited Prostate Cancer Gene
5. Scientists make strides toward drug therapy for inherited kidney disease
6. Drug shown to improve sight for patients with inherited blindness
7. Study: Inherited Alzheimers Detectable 20 Years Before Symptom Onset
8. Inherited Alzheimers detectable 20 years before dementia
9. Stem cell model offers clues to cause of inherited ALS
10. Most common form of inherited intellectual disability may be treatable
11. Immunization not linked to increased hospitalization for children with inherited disorder
Post Your Comments:
(Date:10/12/2015)... ... October 12, 2015 , ... The Horizon Foundation for ... focused on improving public health and enhancing the quality of life in the Garden ... 11 New Jersey non-profit organizations. , The charitable arm of Horizon Blue Cross ...
(Date:10/12/2015)... ... October 12, 2015 , ... ... present the latest version of Companion Mics, the CM•4 Multi-Talker Noise Reduction System, ... Union of Hearing Aid Acousticians’ (EUHA) 60th Annual Congress in Nuremberg, Germany. ...
(Date:10/12/2015)... Town, Maine (PRWEB) , ... October 12, 2015 , ... ... Lake Itasca, MN. Their mission: To paddle the entire 2,320-miles of river to the ... are now halfway done with the monumental journey, with two months remaining for a ...
(Date:10/12/2015)... (PRWEB) , ... October 12, 2015 , ... ... to be a part of a contact channel benchmarking study. Be ... comparisons of key operational strategies for improving customer experience, customer journey, contact channel ...
(Date:10/12/2015)... Colorado Springs, CO (PRWEB) , ... October 12, 2015 , ... NFL football fans who ... to consider donating to a great cause. CLICK HERE to donate to Smile ... and receive an opportunity to win an all-inclusive trip to the 2016 NFL Super Bowl! ...
Breaking Medicine News(10 mins):
(Date:10/12/2015)... , October 12, 2015 ... research report "Spirometer Market by Product (Hand-held, Table-top, Desktop), Technology ... Homecare), Application, & Geography - Global Forecast to 2020", published ... 858.6 Million by 2020, at a CAGR of 9.8% from ... and 128 F igures spread th rough 187 ...
(Date:10/12/2015)... PUNE, India , October 12, 2015 /PRNewswire/ ... The Plague - Pipeline Review, H2 2015 ... helps strengthen plague R&D pipelines by identifying new ... products. . --> ... report on Plague pipeline spread across 62 pages, ...
(Date:10/12/2015)... 2015 Device usage in healthcare continues to ... these devices into existing clinical workflow. In response, Ergotron, ... mobility solutions, has launched the SV10 series of its ... wide array of laptops and tablets. In addition, one ... for Microsoft Surface and is compatible with all Surface ...
Breaking Medicine Technology: