Cancer Genetics Revealing -- St. Jude Leukemia Study Suggests New Treatment Strategies

Mar 27, 08:50 AM

Current Headlines: By Mary Powers powers@commercialappealcom

Tools developed to decipher the human genetic code are being turned on cancer and yielding previously unimaginable detail of the missteps cells take on the road to malignancy.

The results are generating new targets for treatment as well as an enhanced understanding of the molecular basis and complexity of the more than 200 diseases known as cancer.

Writing this month in an on-line edition of the scientific journal Nature, St. Jude Children's Research Hospital investigators describe what they found when they used the tools to study genetic material from young leukemia patients.

"The results were remarkable," said Dr. James Downing, the study's senior author. Downing is also the hospital's scientific director and pathology department chairman. "This suggests the same approach should be used in all cancers."

This study focused on genetic material from 242 St. Jude patients with acute lymphoblastic leukemia (ALL), the most common childhood cancer. It is the largest study yet using techniques that make it possible for investigators to do a gene-by-gene comparison of DNA taken from the the patient's cancerous and normal cells.

St. Jude investigators are now turning these tools on other childhood cancers.

Nationally, the National Cancer Institute pledged $100 million to fund similar efforts at eight institutions. That effort will focus on finding new genetic glitches associated with lung, ovarian and brain tumors.

"A better understanding of cancer genetics is part of the overall effort to eliminate suffering and death due to cancer," explained Dr. Anna Barker, the institute's deputy director. She spoke when the project, known as the Cancer Genome Atlas, was unveiled late in 2005.

Organized into genes, DNA serves as the blueprint for cell function. Cancer results when mistakes arise in that blueprint, sparking the uncontrolled cell division that marks the disease.

In the case of ALL, immature blood cells don't complete the necessary steps to become one of the white blood cells known as B or T lymphocytes. Instead they remain stuck in that immature stage and start multiplying rapidly, with deadly consequences.

Decades of research had already uncovered about 100 mutations associated with ALL. Downing called the leukemia "one of the best characterized types of human cancers and yet using these new techniques we found new and common" damage.

For this study, investigators used chips the size of postage stamps carrying genetic tools that serve as flags and help researchers look for genes in which DNA is missing or changed. In this case, these flags were used to check DNA extracted from the patient's normal and cancerous cells. A laser scanner, detector and powerful computer were used to tabulate and analyze the results.

This study found new, surprisingly common changes in the DNA of the ALL patients. Forty percent had mistakes in one of three genes that are master regulators of immune cells known as B cells. In some cases, bits of DNA were missing and in others there was substitution in the genetic code.

Although it's not clear what causes such changes, Downing said the alterations likely contribute directly to ALL by blocking the normal path immature cells take to become B cells.

The good news is that the findings suggest new strategies for targeting cancer cells, including a new class of drugs to push cells to complete the maturation process. "Then the body would recognize them as defective B lymphocyte (immune cells) and destroy them."

- Mary Powers: 529-2383

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"A better understanding of cancer genetics is part of the overall effort to eliminate suffering and death due to cancer."

Dr. Anna Barker

deputy director National Cancer Institute

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