In almost all cases, the etiology is unknown.
Chronic exposure to certain chemicals (for example benzene) can increase the risk of developing leukemia and myelodysplastic syndrome (MDS). The same applies to long-term treatment with alkylating substances and ionizing radiation. However, very few patients have been exposed to these exogenous factors.
There are indications that mutations in cellular oncogenes, tumor suppressor genes, and transcription factors may be carcinogenic.
Chronic myeloid leukemia is characterized by the presence of the fusion protein bcr-abl. This occurs by the oncogene abl on chromosome 9 moving to the gene area bcr on chromosome 22 t(9;22). This is how the Philadelphia chromosome is created which has a shortened long arm on chromosome 22. See animation:
For chronic lymphatic leukemia, sex (men:women is 2:1) and genetic factors appear to predispose for the disease.
First degree relatives of patients with chronic lymphatic leukemia have a more than 3 times greater chance to develop chronic lymphatic leukemia or other lymphoid malignancy compared to the rest of the population. For chronic lymphatic leukemia, familial disposition is the only well-documented risk factor. It is not unlikely that the disease presents itself earlier and in a more serious form in successive generations.
The disease is very rare in East Asians and the incidence is as low among East Asians living in western countries.
Certain retroviruses can trigger the disease in animals which may indicate that certain viral infections may influence leukemia in humans. Some rare cases of T-cell leukemia are associated with infection of a human retrovirus (HTLV I).