Scientists discover molecular target for treatment of T cell acute lymphoblastic leukemia
A new research study published in the June issue of Cancer Cell identifies the molecular events that contribute to a notoriously treatment-resistant form of T cell leukemia.
The findings reveal that disruption of immune cell differentiation is central to disease progression and provide new avenues for development of future therapeutics.
T cell acute lymphoblastic leukemia (T-ALL) accounts for 10%-15% of pediatric and 25% of adult ALL cases. A gene called TAL1/SCL is frequently activated in T-ALL patients, but exactly how it causes leukemia has not been clear.
Dr. Michelle Kelliher, from the Department of Cancer Biology at the University of Massachusetts Medical School in Worcester, Massachusetts, and colleagues examined how the TAL1/SCL protein contributes to leukemia.
The researchers demonstrate that TAL1/SCL induces leukemia by interfering with a protein called E47/HEB that regulates the expression of many different genes required for immune cell differentiation and survival.
When these genes were experimentally inhibited by TAL1/SC1 in mice, the mice exhibited abnormal immune (T cell) development, and most eventually developed leukemia.
The researchers also showed that TAL1/SCL silences gene expression by recruiting a histone deacetylase (HDAC) repressor complex, and in fact, HDAC inhibitors were very effective at inhibiting the growth of TAL1/SCL tumor cells.
“Our work demonstrates that TAL1/SCL induces leukemia by repressing E47/HEB activity, and suggests that HDAC inhibitors may prove efficacious in T-ALL patients who express TAL1/SCL. This is an important discovery, as these particular patients respond poorly to current chemotherapies and are at high risk for treatment failure,” says Dr. Kelliher.
Jennifer O’Neil, Jennifer Shank, Nicole Cusson, Cornelius Murre, and Michelle Kelliher: “TAL-1/SCL induces leukemia by inhibiting the transcriptional activity of E47/HEB”
Published in Cancer Cell, Volume 5, Number 6, June 2004.
Media Contact
More Information:
http://www.cell.com/All latest news from the category: Life Sciences and Chemistry
Articles and reports from the Life Sciences and chemistry area deal with applied and basic research into modern biology, chemistry and human medicine.
Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.
Newest articles
Endurance Training: Transforming Lives of Heart Failure Patients
Can strength and endurance training be beneficial for patients with a certain form of heart failure? A research team from Greifswald investigated this question together with seven other research centers…
A Wake-Up Call for Mediterranean Shark Protection Against Extinction
Overfishing, illegal fishing and increasing marketing of shark meat pose significant threats to the more than 80 species of sharks and rays that inhabit the Mediterranean Sea, according to a…
Why are Youths’ Mental Health Needs Falling Through the Cracks?
Children and young people with high levels of mental health needs are struggling to receive the help they need, or to have their difficulties recognised, according to a new study….