The environmental exposures that contribute to emergence of ALL is contentious and a subject of ongoing debate.

High levels of radiation exposure from nuclear fallout is a known risk factor for developing leukemia. Evidence whether less radiation, as from x-ray imaging during pregnancy, increases risk of disease remains inconclusive. Studies that have identified an association between x-ray imaging during pregnancy and ALL found only a slightly increased risk. Exposure to strong electromagnetic radiation from power lines has also been associated with a slightly increased risk of ALL. This result is questioned as no causal mechanism linking electromagnetic radiation with cancer is known.

High birth weight (greater than 4000g or 8.8lbs) is also associated with a small increased risk. The mechanism connecting high birth weight to ALL is also not known.

Evidence suggests that secondary leukemia can develop in individuals treated with certain types of chemotherapy, such as epipodophyllotoxins and cyclophosphamide.

Leukemia is rarely associated with pregnancy, affecting only about 1 in 10,000 pregnant women. How it is handled depends primarily on the type of leukemia. Nearly all leukemias appearing in pregnant women are acute leukemias. Acute leukemias normally require prompt, aggressive treatment, despite significant risks of pregnancy loss and birth defects, especially if chemotherapy is given during the developmentally sensitive first trimester. Chronic myelogenous leukemia can be treated with relative safety at any time during pregnancy with Interferon-alpha hormones. Treatment for chronic lymphocytic leukemias, which are rare in pregnant women, can often be postponed until after the end of the pregnancy.

High amounts of ionizing radiation exposure can increase the risk of AML. Survivors of the atomic bombings of Hiroshima and Nagasaki had an increased rate of AML, as did radiologists exposed to high levels of X-rays prior to the adoption of modern radiation safety practices. People treated with ionizing radiation after treatment for prostate cancer, non-Hodgkin lymphoma, lung cancer, and breast cancer have the highest chance of acquiring AML, but this increased risk returns to the background risk observed in the general population after 12 years.

Exposure to anticancer chemotherapy, in particular alkylating agents, can increase the risk of subsequently developing AML. The risk is highest about three to five years after chemotherapy. Other chemotherapy agents, specifically epipodophyllotoxins and anthracyclines, have also been associated with treatment-related leukemias, which are often associated with specific chromosomal abnormalities in the leukemic cells.

Occupational chemical exposure to benzene and other aromatic organic solvents is controversial as a cause of AML. Benzene and many of its derivatives are known to be carcinogenic "in vitro". While some studies have suggested a link between occupational exposure to benzene and increased risk of AML, others have suggested the attributable risk, if any, is slight.

Some people have a genetic predisposition towards developing leukemia. This predisposition is demonstrated by family histories and twin studies. The affected people may have a single gene or multiple genes in common. In some cases, families tend to develop the same kinds of leukemia as other members; in other families, affected people may develop different forms of leukemia or related blood cancers.

In addition to these genetic issues, people with chromosomal abnormalities or certain other genetic conditions have a greater risk of leukemia. For example, people with Down syndrome have a significantly increased risk of developing forms of acute leukemia (especially acute myeloid leukemia), and Fanconi anemia is a risk factor for developing acute myeloid leukemia. Mutation in SPRED1 gene has been associated with a predisposition to childhood leukemia.

Chronic myelogenous leukemia is associated with a genetic abnormality called the Philadelphia translocation; 95% of people with CML carry the Philadelphia mutation, although this is not exclusive to CML and can be observed in people with other types of leukemia.

Leukemia is rarely associated with pregnancy, affecting only about 1 in 10,000 pregnant women. The management of leukemia in a pregnant patient depends primarily on the type of leukemia. Acute leukemias normally require prompt, aggressive treatment, despite significant risks of pregnancy loss and birth defects, especially if chemotherapy is given during the developmentally sensitive first trimester.

JMML accounts for 1-2% of childhood leukemias each year; in the United States, an estimated 25-50 new cases are diagnosed each year, which also equates to about 3 cases per million children. There is no known environmental cause for JMML. Since about 10% of patients are diagnosed before 3 months of age, it is thought that JMML is a congenital condition in these infants

Acute promyelocytic leukemia represents 10-12% of AML cases. The median age is approximately 30–40 years, which is considerably younger than the other subtypes of AML (70 years). Incidence is higher among individuals of Latin American or South European origin. It can also occur as a secondary malignancy in those that receive treatment with topoisomerase II inhibitors (such as the anthracyclines and etoposide) due to the carcinogenic effects of these agents, with patients with breast cancer representing the majority of such patients. Around 40% of patients with APL also have a chromosomal abnormality such as trisomy 8 or isochromosome 17 which do not appear to impact on long-term outcomes.

CML accounts for 8% of all leukaemias in the UK, and around 680 people were diagnosed with the disease in 2011.

CLL is primarily a disease of older adults, with a median age of 70 years at the time of diagnosis. Though less common, CLL sometimes affects people between 30 and 39 years of age. The incidence of CLL increases very quickly with increasing age.

In the United States during 2014, about 15,720 new cases are expected to be diagnosed, and 4,600 patients are expected to die from CLL. Because of the prolonged survival, which was typically about 10 years in past decades, but which can extend to a normal life expectancy, the prevalence (number of people living with the disease) is much higher than the incidence (new diagnoses). CLL is the most common type of leukemia in the UK, accounting for 38% of all leukemia cases. Approximately 3,200 people were diagnosed with the disease in 2011.

In Western populations, subclinical "disease" can be identified in 3.5% of normal adults, and in up to 8% of individuals over the age of 70. That is, small clones of B cells with the characteristic CLL phenotype can be identified in many healthy elderly persons. The clinical significance of these cells is unknown.

In contrast, CLL is rare in Asian countries, such as Japan, China, and Korea, accounting for less than 10% of all leukemias in those regions. A low incidence is seen in Japanese immigrants to the US, and in African and Asian immigrants to Israel.

Of all cancers involving the same class of blood cell, 7% of cases are CLL/SLL.

Rates of CLL are somewhat elevated in people exposed to certain chemicals. Under U.S. Department of Veterans' Affairs regulations, Vietnam veterans who served in-country or in the inland waterways of Vietnam and who later develop CLL are presumed to have contracted it from exposure to Agent Orange and may be entitled to compensation.

Prognosis is generally good relative to other leukemias. Because of the acuteness of onset compared to other leukemias, early death is comparatively more common. The cause of early death is most commonly severe bleeding, often intracranial hemorrhage. Early death from hemorrhage occurs in 5-10% of patients in countries with adequate access to healthcare and 20-30% of patients in less developed countries. Risk factors for early death due to hemorrhage include delayed diagnosis, late treatment initiation, and high white blood cell count on admission. Despite advances in treatment, early death rates have remained relatively constant.

Relapse rates are extremely low. Most deaths following remission are from other causes, such as second malignancies, which in one study occurred in 8% of patients. In this study, second malignancies accounted for 41% of deaths, and heart disease, 29%. Survival rates were 88% at 6.3 years and 82% at 7.9 years.

In another study, 10-year survival rate was estimated to be approximately 77%.

Leukemia is rarely associated with pregnancy, affecting only about one in 10,000 pregnant women. Treatment for chronic lymphocytic leukemias can often be postponed until after the end of the pregnancy. If treatment is necessary, then giving chemotherapy during the second or third trimesters is less likely to result in pregnancy loss or birth defects than treatment during the first trimester.

The exact cause of most cases of childhood leukemia is not known. Most children with leukemia do not have any known risk factors. The immune system plays an important role in protecting the body's immune system. An alteration or defect in the immune system may increase the risk for developing cancer. The immune system can be damaged by different factors, such as exposure to different viruses, environmental factors, chemical factors and other various infections.

There also appears to be some evidence linking childhood leukemia to x-ray exposure. In a 2010 study by the University of California, Berkeley’s School of Public Health, researchers found that children with acute lymphoid leukemia (ALL) had almost twice the chance of having been exposed to three or more X-rays compared with children who did not have leukemia.

Acute erythroid leukemia is rare, accounting for only 3–5% of all acute myeloid leukemia cases. One study estimated an occurrence rate of 0.077 cases per 100,000 people each year. 64–70% of people with this condition are male, and most are elderly, with a median age of 65.

About four men are diagnosed with this disease for every three women. Despite its overall rarity, it is also the most common type of mature T cell leukemia.

T-PLL is an extremely rare aggressive disease, and patients are not expected to live normal lifespans. Before the recent introduction of better treatments, such as alemtuzumab, the median survival time was 7.5 months after diagnosis. More recently, some patients have survived five years and more, although the median survival is still low.

CML is more common in males than in females (male to female ratio of 1.4:1) and appears more commonly in the elderly with a median age at diagnosis of 65 years. Exposure to ionising radiation appears to be a risk factor, based on a 50 fold higher incidence of CML in Hiroshima and Nagasaki nuclear bombing survivors. The rate of CML in these individuals seems to peak about 10 years after the exposure.

As with many cancers, the cause of hairy cell leukemia is unknown. Exposure to tobacco smoke, ionizing radiation, or industrial chemicals (with the possible exception of diesel) does not appear to increase the risk of developing HCL. Farming and gardening appear to increase the risk of HCL in some studies.

Recent studies have identified somatic BRAF V600E mutations in all patients with the classic form of hairy cell leukemia thus sequenced, but in no patients with the variant form.

The U.S. Institute of Medicine (IOM) announced "sufficient evidence" of an association between exposure to herbicides and later development of chronic B-cell leukemias and lymphomas in general. The IOM report emphasized that neither animal nor human studies indicate an association of herbicides with HCL specifically. However, the IOM extrapolated data from chronic lymphocytic leukemia and non-Hodgkin lymphoma to conclude that HCL and other rare B-cell neoplasms may share this risk factor. As a result of the IOM report, the U.S. Department of Veterans Affairs considers HCL an illness presumed to be a service-related disability (see Agent Orange).

Human T-lymphotropic virus 2 (HTLV-2) has been isolated in a small number of patients with the variant form of HCL. In the 1980s, HTLV-2 was identified in a patient with a T-cell lymphoproliferative disease; this patient later developed hairy cell leukemia (a B cell disease), but HTLV-2 was not found in the hairy cell clones. There is no evidence that HTLV-II causes any sort of hematological malignancy, including HCL.

This disease is rare, with fewer than 1 in 10,000 people being diagnosed with HCL during their lives. Men are four to five times more likely to develop hairy cell leukemia than women. In the United States, the annual incidence is approximately 3 cases per 1,000,000 men each year, and 0.6 cases per 1,000,000 women each year.

Most patients are white males over the age of 50, although it has been diagnosed in at least one teenager. It is less common in people of African and Asian descent compared to people of European descent.

It does not appear to be hereditary, although occasional familial cases that suggest a predisposition have been reported, usually showing a common Human Leukocyte Antigen (HLA) type.

Prognosis refers to how well a patient is expected to respond to treatment based on their individual characteristics at time of diagnosis. In JMML, three characteristic areas have been identified as significant in the prognosis of patients:

Without treatment, the survival [5 years?] of children with JMML is approximately 5%. Only Hematopoietic Stem Cell Transplantation (HSCT), commonly referred to as a bone marrow or (umbilical) cord blood transplant, has been shown to be successful in curing a child of JMML. With HSCT, recent research studies have found the survival rate to be approximately 50%. Relapse is a significant risk after HSCT for children with JMML. It is the greatest cause of death in JMML children who have had stem cell transplants. Relapse rate has been recorded as high as 50%. Many children have been brought into remission after a second stem cell transplant.

Chloromas may occur in patients with a diagnosis of myelodysplastic syndrome (MDS) or myeloproliferative syndromes (MPS) (e.g. chronic myelogenous leukemia (CML), polycythemia vera, essential thrombocytosis, or myelofibrosis). The detection of a chloroma is considered "de facto" evidence these premalignant conditions have transformed into an acute leukemia requiring appropriate treatment. For example, presence of a chloroma is sufficient to indicate chronic myelogenous leukemia has entered its 'blast crisis' phase.

Acute mast cell leukemia is extremely aggressive and has a grave prognosis. In most cases, multi-organ failure including bone marrow failure develops over weeks to months. Median survival after diagnosis is only about 6 months.

Information on prognosis is limited by the rarity of the condition. Prognosis appears to be no different to AML in general, taking into account other risk factors. Acute erythroid leukemia (M6) has a relatively poor prognosis. A 2010 study of 124 patients found a median overall survival of 8 months. A 2009 study on 91 patients found a median overall survival for erythroleukemia patients of 36 weeks, with no statistically significant difference to other AML patients. AEL patients did have a significantly shorter disease free survival period, a median of 32 weeks, but this effect was explained by other prognostic factors. That is, AEL is often associated with other risk factors, like monosomal karyotypes and a history of myelodysplastic syndrome. Prognosis is worse in elderly patients, those with a history of myelodysplastic syndrome, and in patients who had previously received chemotherapy for the treatment of a different neoplasm.

In the United States, about 500 patients are diagnosed with Richter's transformation each year.

The 5 year survival has been noted as 89% in at least one study from France of 201 patients with T-LGL leukemia.