Science Article: Abnormal Gene Transcription And Acute Leukemia

November 06, 1997

MEMPHIS, Tenn., November 7, 1997 -- Research over the past 10 years has shown that acute leukemia is in fact a genetic disorder. It arises when genes essential to correct blood cell function are not expressed at the appropriate times. In many cases, the failure of gene expression can be traced to an altered protein known as a transcription factor.

A. Thomas Look, M.D., in an article published in today's issue of Science, estimates that as many as one-half of all childhood leukemia cases result from abnormal transcription factors. Dr. Look, chairman of Experimental Oncology at St. Jude Children's Research Hospital in Memphis, TN, noted that fused transcription factors appear to represent the most common source of new leukemias. These hybrid proteins are formed when normal genes are disrupted by chromosomal breaks and recombine with parts of entirely different genes. Although the fusion products continue to function as transcription factors, their effects on cell growth and development are overriding and can trigger a series of biochemical changes that drive the cell toward leukemic transformation.

Researchers in Dr. Look's laboratory have discovered a novel leukemia-producing transcription factor called E2A-HLF. This fusion protein transforms immature lymphocytes by preventing programs that normally would trigger their destruction. The immortalized cells then accumulate to excessive numbers until they begin to produce the signs and symptoms of leukemia. An important aspect of this discovery, according to Dr. Look, is that it offers a model for studying cell death and cell survival programs in developing lymphocytes. "We know very little about leukemias that result from altered survival signals," explains Dr. Look, "and E2A-HLF may provide a window through which these changes can be understood and related to findings in other childhood tumors."

The close link between fused transcription factors and acute leukemia has enabled treatment specialists to improve their clinical protocols. "Since we know that these genetic alterations produce specific types of leukemia with specific responses to therapy," says Dr. Look, "we are able to modify therapy according to the patient's unique risk of relapse. In the not-too-distant future, we hope to exploit this genetic information to pinpoint new molecular targets for antileukemic drugs and other agents."

St. Jude Children's Research Hospital, in Memphis, Tenn., was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital's work is primarily supported through funds raised by the American Lebanese Syrian Associated Charities (ALSAC). All St. Jude patients are treated regardless of their ability to pay. ALSAC covers all costs of treatment beyond those reimbursed by third party insurers, and total costs for families who have no insurance.

St. Jude Children's Research Hospital

Related Leukemia Articles from Brightsurf:

New therapeutic approach against leukemia
Using an RNA molecule complex, researchers can prevent retention of cancer stem cell in their tumor supporting niche

Nanoparticle for overcoming leukemia treatment resistance
One of the largest problems with cancer treatment is the development of resistance to anticancer therapies.

Key gene in leukemia discovered
Acute myeloid leukemia (AML) is one of the most common forms of blood cancer among adults and is associated with a low survival rate, and leads to the inhibition of normal blood formation.

Vitamin B6, leukemia's deadly addiction
Researchers from CSHL and Memorial Sloan Kettering Cancer Center have discovered how Acute Myeloid Leukemia is addicted to vitamin B6.

Artificial intelligence tracks down leukemia
Artificial intelligence can detect one of the most common forms of blood cancer - acute myeloid leukemia -- with high reliability.

Milestone reached in new leukemia drug
Using a chemical compound called YKL-05-099, a team of cancer researchers from CSHL and the Dana Farber Institute was able to target the Salt-Inducible Kinase 3 (SIK3) pathway and extend survival in mice with MLL leukemia.

The drug combination effective against bovine leukemia
Scientists have succeeded in reducing levels of the bovine leukemia virus (BLV) in cows with severe infections by combining an immune checkpoint inhibitor and an enzyme inhibitor.

Towards a safer treatment for leukemia
An international team of researchers at VIB-KU Leuven, Belgium, the UK Dementia Institute and the Children's Cancer Institute, Australia, have found a safer treatment for a specific type of leukemia.

Research paves way for new source for leukemia drug
Chemistry researchers have patented a method for making anti-leukemia compounds that until now have only been available via an Asian tree that produces them.

An atlas of an aggressive leukemia
A team of researchers led by Bradley Bernstein at the Ludwig Center at Harvard has used single-cell technologies and machine learning to create a detailed 'atlas of cell states' for acute myeloid leukemia (AML) that could help improve treatment of the aggressive cancer.

Read More: Leukemia News and Leukemia Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.