Because of the way the acne drug is thought to work, the results support a new concept of cancer chemotherapy. In the type of leukemia suffered by the patients, white blood cells have turned malignant at an immature stage of cell development. Their arrested development is what renders them practically immortal and dangerous. The acne drug is believed to trigger these immature but malignant cells to divide and mature and then die essentially a natural death. This new concept of triggering cancer cells to mature and die contrasts with the conventional concept of chemotherapy, in which drugs simply poison malignant cells. The drug used in the experimental treatment is known as tretinoin, which belongs to a class of chemicals called retinoic acids that are related to vitamin A. Tretinoin is sold in ointment form as Retin-A, the acne medication produced by Johnson &amp; Johnson's Ortho Pharmaceutical division. The tretinoin used in the leukemia patients, however, is a pill that was prepared for the experiment by chemists at Hoffmann-La Roche Inc., the U.S. arm of Roche Holding Ltd. of Switzerland. Roche, which has a long history of making retinoic acids, sells one of its acids as Accutane, a pill for treating severe acne. The particular form of leukemia that appears to respond readily to the acne-drug type of treatment is called acute promyelocytic leukemia. It is an uncommon cancer, afflicting about 1,000 Americans a year, in which certain cells in the bone marrow become malignant before they have matured into fully functioning white blood cells. The malignant, immature white cells (known as myelocytes) flood the blood stream, producing fatigue, fever, weight loss and bleeding. Until now, chemotherapy with standard anti-cancer drugs has been the only effective treatment for acute promyelocyltic leukemia, but it produces cures in only about a third of patients. The tip-off that an tretinoin-like drug might be effective in treating the leukemia came from a genetic finding, Dr. Raymond P. Warrell Jr. of Memorial Sloan-Kettering and his colleagues in New York and at M.D. Anderson Cancer Center in Houston reported in this week's New England Journal of Medicine. Most patients with promyleocytic leukemia apparently have the same defect in two of their 23 chromosomes, the structures in the cell that contain all the genes. A piece of chromosome number 17 appears to have broken loose and become a part of chromosome number 15. Last year, molecular geneticists identified one of the genes in chromosome 17 that was damaged when the chunk of the chromosome broke loose. The damaged gene, it turned out, ordinarily made a protein -- a receptor -- that grabbed hold of retinoic acid. This and other laboratory findings suggested that the immaturity of the leukemic white blood cells might somehow be related to a foul-up in the way the cells handled or failed to handle retinoic acid. The nature of the genetic damage also hinted that doses of retinoic acids might prod the immature malignant cells to proceed to maturity and then die as normal white blood cells do. "We're now the third group to show remissions {with tretinoin} in this leukemia," following Chinese and French researchers, Dr. Warrell said. But, he added, the U.S. group is the first to show that the drug works by triggering the immature cancer cells to mature, or to "differentiate," in the biologists jargon. "We've documented conclusively that differentiation as a method of cancer therapy in humans is a reality," he said.
A variation of an acne drug may be a potential treatment for adult leukemia according to researchers at Memorial Sloan-Kettering Cancer Center. In this type of leukemia, white blood cells turn malignant at an immature stage of development. The study was published in the journal Nature Communications. The drug is known as tretinoin and is in a class of chemicals called retinoic acid and is related to vitamin A. The form of leukemia that appears to respond is acute promyelocytic leukemia. Patients with this type of leukemia have a piece of chromosome 17 that has reattached to chromosome 15.