Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid)

Article Abstract:

During the normal course of embryonic and fetal development, many cells must replicate themselves again and again. At some point, however, some cells must stop replicating and begin to take on their proper mature characteristics. This process is called differentiation. There are many reasons to draw parallels between cancer cells and the replicating cells which have not yet undergone differentiation. This is especially true in the case of acute promyelocytic leukemia, which constitutes about 15 percent of all adult acute nonlymphoblastic leukemias. This particular leukemia has been associated with a genetic defect that seems to affect the receptor for retinoic acid, a molecule closely related to vitamin A. Retinoic acid and its receptor are believed to play a key role in the regulation of normal differentiation. A study was undertaken to determine if this relationship between differentiation and acute promyelocytic leukemia could be used to therapeutic advantage. Eleven leukemia patients were treated with tretinoin, a variety of retinoic acid with a molecular bond arrangement referred to as "all-trans". Nine of these 11 patients entered complete remission. The analysis of blood samples revealed that the remissions were associated with the maturation of the clones of cells responsible for the leukemia. That is, the tretinoin did not kill the leukemic cells, but rather stimulated them to change from cancerous cells into normal mature cells which do not divide. At the time of the publication of the study results, the remissions had lasted from 1.5 months to more than six months. The tretinoin treatment was well tolerated, with the most common side effect being mild headache. However, two patients did experience an elevation in pressure of their cerebrospinal fluid. Other side effects included skin rash and nasal congestion. Tretinoin appears to be a safe and highly effective agent in the treatment of acute promyelocytic leukemia. (Consumer Summary produced by Reliance Medical Information, Inc.)

Care and treatment, Physiological aspects, Cancer, Cell differentiation

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Acute promyelocytic leukemia

Article Abstract:

Advances in medical research have significantly increased the knowledge about acute promyelocytic leukemia. This type of leukemia was first recognized in the 1950s, and it affects approximately 10% of adults with acute myeloblastic leukemia. Patients with acute promyelocytic leukemia often have a high risk of dying from intracranial or other types of bleeding. Chemotherapy may increase the severity of bleeding episodes. This type of leukemia is characterized by abnormalities in chromosome 15 and chromosome 17. These abnormalities affect the gene for the retinoic acid receptor-alpha and the PML gene. Retinoic acid is involved in the regulation of many different processes in the body. All-trans-retinoic acid was first used to treat patients with promyelocytic leukemia in 1986. An average of 84% of the patients treated in specific clinical trials of all-trans-retinoic acid have gone into complete remission.

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Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide

Article Abstract:

Arsenic trioxide may be effective in patients with acute promyelocytic leukemia who relapse after receiving other treatments. Researchers treated 12 such patients with low doses of arsenic trioxide until bone marrow biopsies contained no cancerous cells. Eleven patients went into remission after 12 to 39 days of treatment. In 8 patients, cancerous cells were eliminated from the bone marrow. Side effects included rash, fatigue, musculoskeletal pain and lightheadedness.

Arsenic compounds, Myeloid leukemia, Myelocytic leukemia

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