Leukemia isn’t caused by a single thing. It develops when DNA in blood-forming cells of the bone marrow becomes damaged, causing those cells to grow out of control instead of maturing into normal white blood cells. In most cases, no single cause can be pinpointed. But several well-established risk factors, from chemical exposures to genetic conditions to prior cancer treatment, can significantly raise the likelihood of developing it.
What Happens Inside the Bone Marrow
Your bone marrow constantly produces new blood cells: red cells that carry oxygen, platelets that help with clotting, and white cells that fight infection. Leukemia starts when one of these immature blood-forming cells acquires a genetic mutation that tells it to keep dividing without maturing properly. The result is a flood of abnormal white blood cells that crowd out healthy ones, which is why leukemia causes symptoms like frequent infections, easy bruising, and fatigue.
Different mutations lead to different types of leukemia. Some forms grow quickly (acute leukemia) and others progress slowly over years (chronic leukemia). The type also depends on which kind of white blood cell is affected. What all forms share is that same basic problem: damaged DNA in the bone marrow disrupts the normal assembly line of blood cell production.
Chemical and Environmental Exposures
Benzene is the most firmly established chemical cause of leukemia, particularly acute myeloid leukemia (AML). It’s found in gasoline, industrial solvents, and cigarette smoke. Workers in petroleum refining, rubber manufacturing, and chemical plants have historically faced the highest exposures. Research indicates the link between benzene and AML is tied to heavy, sustained exposure, with a likely threshold of 50 or more parts-per-million-years of cumulative exposure needed to trigger leukemia development. That’s far above what most people encounter in daily life, but it explains why certain occupations carry elevated risk.
Formaldehyde, certain pesticides, and some industrial solvents have also been linked to increased leukemia risk, though the evidence is not as strong as it is for benzene.
Radiation Exposure
Ionizing radiation damages DNA directly, and the bone marrow is one of the most radiation-sensitive tissues in the body. Studies of medical X-ray workers exposed to low doses over long careers found a meaningful increase in leukemia risk. A large study of Chinese X-ray workers showed that for every 100 milligray of cumulative radiation absorbed by the bone marrow, the excess risk of myeloid leukemia roughly doubled. A meta-analysis pooling data from multiple studies estimated a 19% increase in leukemia risk per 100 milligray of exposure.
To put that in perspective, a single chest X-ray delivers a tiny fraction of a milligray. The concern is really about repeated or high-dose exposures: people who underwent radiation therapy, nuclear industry workers, or survivors of nuclear accidents. Routine medical imaging at normal frequencies does not deliver enough radiation to meaningfully increase leukemia risk for most people.
Smoking
Cigarette smoke contains benzene along with radioactive compounds (lead-210 and polonium-210) that originate largely from the high-phosphate fertilizers used in tobacco farming. Both are established causes of leukemia on their own, and together they make smoking a significant risk factor for AML. A case-control study from Los Angeles County estimated that smoking was responsible for roughly 42% of cases of a specific AML subtype, with smokers facing about 2.3 times the odds of developing it compared to nonsmokers. Not all AML subtypes show the same degree of risk increase, but the connection between smoking and blood cancers is well supported.
Previous Cancer Treatment
Certain chemotherapy drugs and radiation therapy can damage bone marrow DNA in ways that lead to “treatment-related” leukemia years later. This is one of the more unsettling risk factors because it’s a consequence of surviving one cancer. The risk is highest in the first 10 to 15 years after treatment, when the cumulative incidence of developing a secondary leukemia (usually AML) plateaus at roughly 2%.
But the risk doesn’t disappear entirely after that window. A study following childhood cancer survivors found 13 confirmed cases of leukemia occurring 15 or more years after the original diagnosis, with an average gap of about 21.6 years. The overall 30-year cumulative incidence was low, around 0.31%, but it underscores the importance of long-term monitoring for cancer survivors. The types of chemotherapy drugs most associated with this risk are alkylating agents and drugs that target a specific enzyme involved in DNA repair.
Genetic Conditions and Family History
Some people are born with a higher baseline risk. The clearest example is Down syndrome. Children with Down syndrome face an estimated 500-fold higher risk of developing acute megakaryocytic leukemia compared to other children. This dramatic increase is linked to mutations in a gene called GATA1, which controls how certain blood cells mature. When GATA1 doesn’t function properly, immature blood cells proliferate instead of developing normally, and in some cases this progresses to full leukemia.
Other inherited conditions that raise leukemia risk include Li-Fraumeni syndrome, Fanconi anemia, and certain inherited immune deficiencies. Having a first-degree relative (parent, sibling) with chronic lymphocytic leukemia also modestly increases your risk, suggesting a genetic component even in people without a named syndrome. Still, the vast majority of leukemia cases occur in people with no family history of the disease.
Viral Infections
One virus has a direct, proven link to a specific type of leukemia. Human T-lymphotropic virus type 1 (HTLV-1) can cause adult T-cell leukemia/lymphoma, a rare and aggressive blood cancer. According to the World Health Organization, the lifetime risk of developing this leukemia among people infected with HTLV-1 is about 5%. The virus spreads through breastfeeding, sexual contact, blood transfusions, and shared needles.
HTLV-1 is most common in parts of Japan, the Caribbean, South America, and sub-Saharan Africa, infecting an estimated 5 to 10 million people worldwide. The latency period between infection and leukemia development is typically decades, meaning most carriers never develop cancer. But for those who do, the long silent period means the infection is often acquired in childhood and doesn’t cause problems until middle age or later.
Age and Factors You Can’t Control
The single biggest risk factor for most types of leukemia is simply getting older. As bone marrow stem cells divide over a lifetime, they accumulate random DNA mutations. Most of these mutations are harmless, but occasionally one hits a gene that controls cell growth. This is why AML and chronic lymphocytic leukemia are most commonly diagnosed in adults over 65. Acute lymphoblastic leukemia is the exception: it peaks in children between ages 2 and 5, driven by different biological mechanisms.
Men develop leukemia at slightly higher rates than women across nearly all subtypes, though the reasons aren’t fully understood. Prior blood disorders like myelodysplastic syndromes, where the bone marrow produces abnormal cells without yet being cancerous, can also progress to leukemia over time.
Why Most Cases Have No Clear Cause
Despite all these known risk factors, the majority of people diagnosed with leukemia can’t point to a specific exposure, condition, or behavior that caused it. Most leukemia arises from random mutations that accumulate during normal cell division. Two people with identical exposures and genetic backgrounds can have completely different outcomes. The risk factors above shift the odds, sometimes dramatically, but they don’t guarantee disease. Conversely, having none of them doesn’t make you immune. This randomness is frustrating, but it also means that for most people, leukemia is not something they could have prevented.