New Gene Alteration Find Points To Aggressive Leukemia Treatment

January 28, 1998

COLUMBUS, Ohio -- Researchers looking at a group of leukemia patients have found that a genetic defect they discovered two years ago serves as an early warning signal, calling for a speed-up in these patients’ treatment.

The defect is a duplication of a small part of the ALL1 gene. Patients who have this alteration fall out of remission three times faster than those who don’t and their survival is slightly more than half that of patients who don’t have the defect.

The scientists reported their discovery in the journal Cancer Research.

The gene defect appears in patients suffering from acute myeloid leukemia (AML), a cancer that afflicts about one in 100,000 people. The disease increases as the population ages and the prognosis of patients with the disease worsens with age. Perhaps 40 percent of those with AML can be cured using appropriate therapies. Without treatment, AML can kill in a few months.

“This is one of only a few instances where we’ve cloned a gene and then figured out what it means in terms of an individual patient’s disease. What’s more, this gene defect is a sign of a poor prognosis. Finding it allows us to better plan a patient’s treatment,” explained Michael Caligiuri, co-director of the division of hematology and oncology and associate director for clinical cancer research for Ohio State University’s Comprehensive Cancer Center. The study was led by Caligiuri and Dr. Clara Bloomfield, director of the CCC and of the division of hematology and oncology.

In approximately 55 percent of the cases of AML, the patient’s chromosomes show distinctive changes that can be linked to the disease. In the remaining 45 percent however, the patients show normal cytogenetics -- that is, there are no obvious chromosomal changes.

This particular defect appears in patients who have normal cytogenetics, Caligiuri said. That is, a typical inspection of the patient’s chromosomes shows none of the chromosomal changes that signal the cause of AML.

Caligiuri and his colleagues examined 98 patients diagnosed with AML but who had normal chromosomes. In 11 of these patients, a closer examination showed that a short segment of the ALL1 gene had been duplicated and spliced back into the gene. In every case with these patients, their prognosis was more serious than that of patients lacking this defect.

Patients with the defect remained in remission from the disease just over seven months while those without the defect maintained remission for nearly two years. The survival time for patients in the study who had the defect was just under 14 months while patients without the defect had an average survival of 20 months.

“This means that about 5 percent of patients with AML have this defect and need to be treated quickly and aggressively,” Caligiuri said, adding that patients with the defect probably should undergo an allogenic bone marrow transplant while in their first remission of the disease if that option is a possibility.

The researchers are now beginning a larger, more comprehensive prospective study intended to validate their retrospective study. Next, they will test the effectiveness of aggressive therapy in patients with the ALL1 defect. Caligiuri suggests that a screening test for the defect, now available at Ohio State, should be widely available this year. The international collaboration was funded by the Leukemia Society of America, the Lady Tata Memorial Fund, the Cancer Society of Finland and the Coleman Leukemia Research Fund.

Ohio State University

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events 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