|Chronic myelagenous leukemia, CML
Chronic myelagenous leukemia (CML) is also referred to as Chronic Myeloid, Chronic Myelocytic and Chronic Granulocytic Leukemia. CML is a clonal proliferation caused by malignant transformation of a pluripotent cell. The characteristic of CML is overproduction of granulocytes (neutrophils, eosinophils and basophils). Marrow invasion replaces all cells leading to increased red blood cell, platelet and white blood cell counts. The clinical course is slowly progressive. Median survival is approximately 40 months, when acute leukemia develops.
Symptoms of CML include fatigue, purpura, hives and pruritis due to histamine release. Signs include anemia, purpura, swollen gums (due to cellular infiltrate), splenomegaly, and chloroma (red-brown skin papules that become green when blood is squeezed out).
A blood smear will show moderately elevated white blood cells (mostly myelocytes), which may persist for years and be benign. Basophils are elevated and marrow mast cells are increased. Platelets are increased in number although their function is impaired. Serum B12 levels are markedly increased, and uric acid levels are elevated.
The goal of treatment is palliation, not cure. With chemotherapy, usually the patient may be kept asymptomatic for long periods by keeping the white blood cell count below 50,000/uL.
Chronic myelagenous leukemia may be caused by ionizing radiation or other chromosomal damage that opens oncogenes. Incidence of CML is increased in patients with Down syndrome (abnormal chromosome 21) and Philadelphia chromosome (translocation of an oncogene from chromosome 9 to chromosome 22).
The Philadelphia chromosome translocation leads to the formation of a new protein called bcr-abl, which acts as an oncogene to cause CML cells to develop and grow.
The cause of CML is unknown, but it has been linked to exposure to benzene and high doses of radiation.
Risk factors are thought to include some combination of viruses (e.g. Epstein-Barr virus-associated lymphoproliferative disorder, EBV-LPD), genetic and immunologic factors, and exposure to radiation and certain chemicals.
One specific enzyme, tyrosine kinase, is believed to cause more than 97 percent of all cases. Druker and researchers from Novartis Pharmaceuticals found a way to stop that enzyme six years ago and have been testing and refining it ever since with a compound called STI-571, also called Gleevec. Gleevec is a chemical inhibitor of the Bcr/Abl tyrosine kinase,
Myelotoxic agents (eg, ionizing radiation, benzene, alkylating agents)
Damage to the bone marrow by agents, such as benzene and ionizing radiation, may cause CML.
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