Leukemia is caused by genetic changes in blood-forming cells that make them grow out of control and resist the normal signals telling them to die. These changes can be triggered by a range of factors, including chemical exposures, radiation, inherited genetic conditions, certain viruses, and previous cancer treatment. In many cases, no single identifiable cause can be pinpointed.
How Normal Blood Cells Become Leukemic
Your bone marrow contains stem cells that continuously produce new blood cells: white blood cells, red blood cells, and platelets. These stem cells divide, mature through several stages, and eventually become fully functional blood cells. Leukemia starts when one or more of these cells picks up a genetic mutation that disrupts this orderly process.
The mutation gives the affected cell two dangerous abilities. First, it can keep copying itself indefinitely, something normal maturing blood cells lose the ability to do. Second, it often stops maturing properly, so the bone marrow fills with immature, non-functional cells that crowd out healthy ones. This is why leukemia causes symptoms like fatigue, frequent infections, and easy bruising: the body can no longer make enough normal blood cells.
A single mutation is rarely enough. Research from the National Academy of Sciences shows that fully malignant leukemia typically requires additional mutations or changes in gene activity on top of the initial triggering event. One mutation might cause cells to multiply too quickly, while a second prevents them from dying on schedule. The accumulation of these hits over time is what ultimately transforms a slightly abnormal cell into a leukemic one.
Childhood vs. Adult Leukemia: Different Origins
Leukemia in children is not simply a younger version of adult leukemia. A major study from the National Cancer Institute found that the genetic landscapes of childhood and adult acute myeloid leukemia (AML) are strikingly different. In adults, AML tends to result from the slow accumulation of multiple small mutations over a lifetime. In children, large structural rearrangements in DNA, where whole sections of chromosomes break and rejoin in the wrong place, are far more common and appear potent enough to cause cancer on their own.
Even the specific genes involved differ. Mutations in the NRAS gene, which controls cell growth and death, are much more frequent in pediatric AML than in adult cases. These distinctions matter because treatments developed for adults don’t always work for children, precisely because the underlying biology is different.
Chemical Exposures, Especially Benzene
Benzene is the most well-established chemical cause of leukemia, particularly AML. It’s found in gasoline, industrial solvents, and cigarette smoke. When your body breaks down benzene, its byproducts damage DNA in bone marrow cells and impair the cell’s ability to repair that damage.
A large Swiss cohort study found that the risk of dying from AML increased in a dose-dependent fashion with occupational benzene exposure. Workers with the highest exposure levels had roughly 35 to 39% higher risk compared to unexposed individuals. Even moderate exposure showed a trend toward increased risk, though the effect was smaller. People who work in petroleum refining, chemical manufacturing, shoe production, and other industries with regular benzene contact face the greatest risk.
Cigarette smoking is another significant source of benzene. Smokers have a modestly elevated risk of myeloid leukemias. Beyond benzene, tobacco smoke contains other chemicals shown to cause chromosome damage in bone marrow cells, which may explain why smoking also worsens outcomes for people who develop AML.
Radiation Exposure
Ionizing radiation, the type produced by nuclear reactions, X-rays, and certain industrial equipment, is a proven leukemia trigger. The clearest evidence comes from survivors of the atomic bombings in Japan, who showed a sharp increase in myeloid leukemias within just a few years of exposure.
A large international study of radiation-monitored workers (the INWORKS cohort) confirmed that even occupational doses of radiation over a career increase leukemia risk. The excess relative risk of leukemia death was roughly three times higher per unit of cumulative radiation dose, with the effect appearing after a latency period as short as two years. This short lag between exposure and disease is unusual among radiation-related cancers, most of which take a decade or more to develop. Chronic lymphocytic leukemia (CLL) is the notable exception and does not appear strongly linked to radiation.
Previous Cancer Treatment
Some of the same therapies used to treat one cancer can, years later, cause a secondary leukemia. Two classes of chemotherapy drugs carry the highest risk. Alkylating agents, commonly used against breast cancer, lymphoma, and other solid tumors, can cause a form of secondary AML that typically appears five to seven years after treatment. This type often involves the loss of parts of chromosomes 5 or 7 and is frequently preceded by a period of abnormal blood counts called myelodysplasia.
The second class, topoisomerase II inhibitors (including drugs like etoposide and doxorubicin), causes a different pattern. These drugs trigger rearrangements in a gene on chromosome 11 and tend to produce leukemia on a shorter timeline, sometimes within one to three years of treatment. Because these treatment-related leukemias arise through distinct genetic pathways, they often behave differently from leukemias that develop on their own.
Inherited Genetic Conditions
Certain genetic syndromes substantially raise a person’s risk. Down syndrome is the most well-known example. Children with Down syndrome, who carry an extra copy of chromosome 21, are at significantly elevated risk of developing a specific type of myeloid leukemia in early childhood. The mechanism involves a cooperation between the extra chromosome and mutations in a gene called GATA1 that controls blood cell development. Research has shown that this combination, the extra chromosome 21 plus the GATA1 mutation, creates a uniquely leukemia-prone state regardless of which change comes first.
Other inherited conditions that increase leukemia risk include Li-Fraumeni syndrome, Fanconi anemia, and certain familial predisposition syndromes where mutations affecting blood cell development run in families.
The Philadelphia Chromosome
One of the best-understood genetic events in leukemia is the Philadelphia chromosome, found in nearly all cases of chronic myeloid leukemia (CML). It forms when pieces of chromosomes 9 and 22 swap places, fusing two genes (BCR and ABL) that don’t normally sit together. The resulting fusion protein acts like an always-on growth signal. It reduces the cell’s need for normal growth factors, blocks the cell’s self-destruct mechanism, and alters how cells stick to their surroundings in the bone marrow.
This discovery was transformative for treatment. Because the disease depends so heavily on this single abnormal protein, drugs that specifically block its activity have turned CML from a near-certain death sentence into a manageable chronic condition for most patients.
Viral Causes
One virus is directly linked to leukemia: human T-cell leukemia virus type 1 (HTLV-1), which causes adult T-cell leukemia/lymphoma. An estimated 10 million or more people worldwide carry the virus, though the true number is likely higher because many endemic regions haven’t been systematically studied. About 5% of infected people eventually develop this aggressive leukemia.
The virus works through a slow, indirect process. HTLV-1 doesn’t insert a cancer gene into the cell. Instead, it produces proteins that promote infected cell division and help those cells evade the immune system. Over decades, this persistent cell turnover generates copying errors in the cell’s DNA. Eventually, enough of these errors accumulate to produce a fully malignant clone. This explains why HTLV-1 leukemia almost always appears in adults who were infected early in life, often through breastfeeding. The two key risk factors are a long duration of infection and a high number of virus-carrying cells in the blood.
When No Cause Is Found
For many people diagnosed with leukemia, none of these identifiable triggers apply. They were never exposed to high levels of benzene or radiation, they don’t have an inherited syndrome, and they never received chemotherapy for a prior cancer. In these cases, the mutations driving the disease likely arose from random errors during normal cell division. Every time a cell copies its DNA, there’s a small chance of a mistake. Over millions of cell divisions across a lifetime, some of these errors can land in the wrong genes. This element of biological randomness is why leukemia risk rises with age for most subtypes and why it can occur in otherwise healthy people with no known exposures.