Salk Scientists Unlock Workings of Cells That Cause Rare Leukemia : Health: Findings may improve treatment of disease and aid research into cures for other cancers.
Salk Institute researchers have uncovered the molecular blueprint of renegade cells that cause an unusual leukemia--a discovery that could allow doctors to detect the disease sooner and improve existing treatments, according to a report released today.
Doctors have long understood that a form of vitamin A is effective in treating the disease, but uncovering the molecular culprit that causes this rare leukemia enables them to learn why the remedy works, said the Salk researchers who collaborated with scientists from New York’s Memorial-Sloan Kettering Cancer Center.
Scientists said he findings, published in today’s issue of Cell journal, could be applied to developing gene therapies to battle other more common cancers.
“These discoveries provide foundations upon which new directions, diagnosis and treatment can be based,” said Dr. Albert B. Deisseroth, chairman of the department of hematology at the M.D. Anderson Cancer Center in Houston. “The principle of elucidating a molecular change will serve as a model, which will trigger developments in much more common diseases.”
Acute promyelocytic leukemia, or APL, is a rare form of adult leukemia, striking 15% of the nation’s 30,000 leukemia patients. In a normal healthy body, white blood cells--which fight infection--mature and die. In a leukemia patient, the cells keep dividing and do not mature and die. The wildly growing cells push aside white cells, red oxygen-carrying cells and platelets that control bleeding.
Doctors also already knew that the leukemia caused two chromosomes to fuse together inside the cells of most APL patients. Yet, they had figured out little else about this puzzling development.
But, in the findings published today, Dr. Ronald M. Evans, head of Salk’s Gene Expression Laboratory, and his colleagues isolated the blueprints of this fusion and discovered that it produced a new protein molecule. Evans, an author of the report, suggests that the new molecule blocks the ability of normal molecules to promote maturing of the affected white blood cells, trapping them in a state of constant dividing.
Doctors had reported that retinoic acid, a form of vitamin A, causes the wildly multiplying APL cancer cells to reverse themselves and change back into normal white blood cells.
What the new research shows them is why this works: When retinoic acid is introduced it attaches to the new molecule, unblocking normal activity--reversing the course of the disease.
“The broader impact is, if we can find that other types of cancers have similar origins, we may be able to develop tools or substances that work like retinoic acid,” said Kenneth Klivington, who is in charge of scientific programming at Salk. “But we don’t know yet how many types of cancer are due to similar types of genetic affects.”
For those afflicted with the rare leukemia, the findings will allow doctors to improve treatments because they now know exactly what molecule to target. The existing treatment has side effects, including skin rashes and headaches, that doctors say might now be eliminated.
“We’ll be able to make the therapy more effective and to make our therapy more selective so it’s specifically toxic to leukemia cells and non-toxic to normal cells,” Deisseroth said.
The discovery of the new molecule will also serve as a red flag to doctors, alerting them early to the presence of the leukemia.
“With existing techniques, the fact that a person has APL might be overlooked, but with the information now available, it’s possible to detect the broken genes at a very early stage of the cancer,” said Klivington, adding that a routine blood test could be used to show whether APL is present.
At Salk, Akira Kakizuka and Kazuhiku Umesono joined Evans in studying the disease. Wilson H. Miller Jr., Raymond P. Warrell Jr., Stanley R. Frankel, Vundavali V.V.S. Murty and Ethan Dmitrovsky of Memorial-Sloan Kettering co-authored the report.
