The exact cause of leukemia is unknown.
- As with other cancers, smoking is considered a risk factor for leukemia, but many people who develop leukemia have never smoked, and many people who smoke never develop leukemia.
- Long-term exposure to chemicals such as benzene or formaldehyde, typically in the workplace, is considered a risk factor for leukemia, but this accounts for relatively few cases of the disease.
- Prolonged exposure to radiation is a risk factor, although this accounts for relatively few cases of leukemia. Doses of radiation used for diagnostic imaging such as x-rays and CT scans are nowhere near as prolonged or high as the doses needed to cause leukemia.

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Other risk factors for leukemia include the following:
- Previous chemotherapy: Chemotherapy, particularly certain of the alkylating agents and topoisomerase inhibitors, used to treat certain types of cancers, are linked to development of leukemia later. It is likely that radiation treatment adds to the risk of leukemia associated with certain chemotherapy drugs.
- Human T-cell leukemia virus 1 (HTLV-1): Infection with this virus is linked to human T-cell leukemia.
- Myelodysplastic syndromes: In this unusual group of blood disorders, the net outcome is invariably an acute myelocytic process.
- Down syndrome and other genetic diseases: Some diseases caused by abnormal chromosomes may increase risk for leukemia.
- Family history: Having a first-degree relative (parent, brother, sister, or child) who has chronic lymphocytic leukemia increases one’s risk of having the disease by as much as 4 times that of someone who does not have an affected relative.
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