Leukemia starts when DNA in a single blood-forming cell in your bone marrow mutates and begins producing abnormal white blood cells that crowd out healthy ones. There is no single cause. Instead, a combination of genetic changes, environmental exposures, and sometimes pure chance determines who develops the disease. Most people diagnosed with leukemia have no obvious risk factor at all.
What Happens Inside the Bone Marrow
Your bone marrow constantly produces new blood cells from a small pool of stem cells. Each time one of these stem cells divides, there’s a tiny chance of a copying error in its DNA. Most of these errors are harmless. But when a mutation lands in a gene that controls cell growth, survival, or maturation, the affected cell can gain an advantage over its neighbors, dividing faster or refusing to die on schedule.
Leukemia rarely results from a single mutation. It typically develops through a multi-step process where early mutations (often in genes that regulate how DNA is read or maintained) create a pre-leukemic state. The cell looks mostly normal but is primed for trouble. Later, additional mutations in genes that control cell signaling or the development of mature blood cells push the clone over the edge into full-blown leukemia. Research published in Blood found that in cases progressing from a precursor condition to acute myeloid leukemia, 78% of the new mutations involved genes controlling either cell signaling or the instructions for building functional blood cells. This layered process explains why leukemia is far more common in older adults: more years of cell division means more opportunities for dangerous mutations to stack up.
Age Is the Strongest Risk Factor
Although leukemia is one of the most common childhood cancers, it overwhelmingly strikes older people. According to National Cancer Institute data, over 75% of new cases occur in people 55 and older. Nearly a third are diagnosed in people 75 and up. Only about 7% of cases occur in people under 20. The types also shift with age: acute lymphoblastic leukemia (ALL) peaks in early childhood, while acute myeloid leukemia (AML) and chronic forms become more common later in life. About 67,790 new cases are expected in the U.S. in 2026.
Chemical and Occupational Exposures
Benzene is the best-established chemical cause of leukemia. It’s found in gasoline, industrial solvents, cigarette smoke, and certain manufacturing processes. A landmark epidemiologic study found that workers with the highest cumulative benzene exposure (400 or more ppm-years, equivalent to breathing an average of 10 parts per million over a 40-year career) had a leukemia death rate more than 66 times higher than expected. Even moderate exposure levels showed elevated risk, with mortality climbing in a clear dose-response pattern.
Formaldehyde is another occupational hazard. Studies of industrial workers, embalmers, and laboratory technicians exposed to high levels have linked it to myeloid leukemia specifically. People who manufacture formaldehyde-containing products or work in mortuaries face the greatest exposure.
For most people, everyday contact with these chemicals is far below occupational levels. The risk is concentrated among workers with prolonged, heavy exposure and without adequate protective equipment.
Radiation Exposure
Ionizing radiation, the kind produced by nuclear reactions, certain medical imaging, and radiotherapy, damages DNA directly and is a well-documented leukemia trigger. What’s striking is how low the threshold appears to be. A large study of radiation workers found excess leukemia-related deaths even among those who had accumulated less than 5 milligray of exposure, a very small dose. More than half of the leukemia deaths in that study (53%) occurred in the lowest-dose group. This doesn’t mean a single X-ray is dangerous, but it does suggest there may be no perfectly “safe” threshold for cumulative radiation exposure over a lifetime.
Previous Cancer Treatment
One of the more unsettling risk factors is prior chemotherapy or radiation therapy for a different cancer. This is called therapy-related leukemia, and it accounts for a meaningful fraction of AML cases. The classes of drugs most strongly linked include alkylating agents (used in many standard chemotherapy regimens), topoisomerase II inhibitors (common in breast cancer and lymphoma treatment), platinum-based drugs, and a newer class of targeted drugs called PARP inhibitors. Broad-field radiation therapy also contributes, though modern techniques that focus the beam more precisely are reducing this risk.
The type of leukemia that develops depends partly on the treatment received. Alkylating agents tend to cause leukemia with specific chromosome deletions, typically appearing five to seven years after treatment. Topoisomerase II inhibitors are linked to a different genetic pattern and can cause leukemia within one to three years. This is one of the difficult trade-offs in cancer care: the treatment that cures one malignancy can, in rare cases, plant the seed for another.
Smoking
Cigarette smoke contains benzene and other carcinogens, so a link to leukemia makes biological sense. The overall association is modest: smokers have roughly a 20% higher risk of AML compared to nonsmokers. But for certain subtypes and age groups, the effect is larger. One case-control study found that smokers aged 60 to 75 had more than three times the risk of a specific AML subtype compared to nonsmokers. Smoking is the one major leukemia risk factor that is entirely within your control.
Inherited Genetic Conditions
Certain genetic syndromes substantially raise leukemia risk from birth. The most well-known is Down syndrome: children with this condition have a 10- to 45-fold increased risk of leukemia compared to other children. Other inherited conditions that increase risk include Li-Fraumeni syndrome (caused by mutations in the TP53 tumor suppressor gene), Fanconi anemia, and several other rare DNA repair disorders.
These syndromes don’t guarantee leukemia will develop. They create a higher baseline vulnerability, often because the affected genes are involved in repairing DNA damage or controlling cell growth, the same pathways that go wrong in leukemia generally.
Family History
Having a close relative with leukemia does appear to raise your risk, though the size of the effect is debated. One large study estimated that a first-degree family history of leukemia was associated with roughly 1.2 to 2.4 times the normal risk, depending on how the data were analyzed. A family history of other blood cancers showed a similar pattern. These numbers suggest a real but modest genetic component for most people. The vast majority of leukemia cases occur in families with no prior history of the disease.
Viral Infections
One virus has a direct, proven link to leukemia. Human T-cell lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia, a rare and aggressive form of the disease. The virus infects T-cells and produces proteins that cause DNA breaks, disable the cell’s normal damage-repair systems, and promote uncontrolled cell division. But the process is slow. HTLV-1 carriers may be infected for decades before leukemia develops, and only a small percentage of infected people (estimated at 2 to 5% over a lifetime) ever progress to leukemia. The longer the infection persists and the higher the viral load, the greater the risk of accumulating the multiple mutations needed for full transformation.
HTLV-1 is most common in parts of Japan, the Caribbean, Central Africa, and South America. It spreads through breastfeeding, sexual contact, blood transfusions, and shared needles.
Why Most Cases Have No Clear Cause
Despite all these known risk factors, most people who develop leukemia can’t point to a specific reason. The majority of the critical mutations arise from ordinary errors during cell division, not from any identifiable exposure. Every time a stem cell copies its 6 billion DNA letters to make a new cell, mistakes slip through. Over decades, some people accumulate the unlucky combination of mutations that tips a cell toward leukemia. This randomness is a large part of why leukemia risk rises so sharply with age and why it can strike people with no risk factors whatsoever.