Navigation Links
Inherited DNA change explains overactive leukemia gene
Date:5/25/2012

  • 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
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Medical Center
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... ProVest Insurance Group, ... Dallas, Miami, and Raleigh regions, is organizing an extended charity drive to benefit ... deadly chromosome abnormality. , After struggling since birth with several health challenges, T.J. ...
(Date:10/13/2017)... ... October 13, 2017 , ... The ... to promote standards of excellence for the field of eating disorders, announces the ... – 25, 2018 in Orlando, Florida at the Omni Resort at ChampionsGate. ...
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... Many families ... However, many long-term care insurance companies have a waiver for care if the client ... elimination period, when the family pays for care, is often waived, so the benefits ...
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... ... will be giving viewers the lowdown on sciatica in a new episode of ... that focuses on current events and innovation and investigates each subject in-depth with ...
(Date:10/12/2017)... ... October 12, 2017 , ... ... sleep apnea using cutting-edge Oventus O2Vent technology. As many as 18 ... characterized by frequent cessation in breathing. Oral appliances can offer significant relief to ...
Breaking Medicine News(10 mins):
(Date:10/4/2017)... the Centers for Disease Control and Prevention (CDC), influenza vaccination should ... helping communities across Massachusetts , Connecticut ... shots through the end of the month. *Some exclusions apply ... ... is by the end of October, according to the Centers for Disease ...
(Date:10/2/2017)...  Eli Lilly and Company (NYSE: LLY ... quarter of 2017 on Tuesday, October 24, 2017. Lilly ... with the investment community and media to further detail ... will begin at 9 a.m. Eastern time. Investors, media ... of the conference call through a link that will ...
(Date:10/2/2017)... COPENHAGEN, Denmark , Oct. 2, 2017 The ... tool in the struggle to reverse the tide of prescription ... plan for regulating their medicine intake and stepping down their ... is set to launch in December 2017; the first 100,000 ... access. Learn more at http://www.rebound-solution.com/ ...
Breaking Medicine Technology: