Leukemia is a cancer affecting the blood-forming tissues of the body, including the bone marrow and the lymphatic system. The disease is driven by changes in the DNA of blood cells. While all leukemia is genetic because it stems from gene mutations, most of these are not inherited from a parent. The majority of cases arise from genetic damage acquired during a person’s lifetime.
The Role of Acquired Gene Mutations
The development of most leukemia cases is traced to somatic mutations. These are genetic alterations that occur after conception and are acquired during a person’s life. Somatic mutations are not present in every cell of the body; they are confined to the specific cell where the error first arose and its descendants. These changes are not passed from parent to child.
These mutations happen in a single blood-forming stem cell within the bone marrow. The alterations disrupt the normal instructions that govern cell growth and development, leading to the uncontrolled production of abnormal white blood cells. These leukemia cells then multiply and crowd out healthy blood cells in the bone marrow. This interference with normal blood cell production leads to the symptoms associated with the disease.
A well-documented example of an acquired mutation is the Philadelphia chromosome. This abnormality is the result of a translocation, where a piece of chromosome 9 breaks off and attaches to chromosome 22. This event creates a new, fused gene called BCR-ABL1. The protein produced by this fusion gene is an enzyme called a tyrosine kinase, which is constantly active and drives the rapid and uncontrolled growth of leukemia cells.
This specific mutation is a hallmark of chronic myeloid leukemia (CML) and is also found in some cases of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). This knowledge directly led to the development of targeted therapies, such as tyrosine kinase inhibitors (TKIs). These drugs are designed to block the action of the BCR-ABL1 protein and have transformed the prognosis for many patients.
Inherited Genetic Syndromes and Leukemia Risk
While most leukemia is not hereditary, a small percentage of cases, around 5-10%, are linked to an inherited genetic predisposition. In these instances, individuals are born with a germline mutation, which is a change in the DNA that is present in every cell of their body. This means the mutation can be passed from one generation to the next. These germline mutations do not guarantee that a person will develop leukemia, but they do increase the lifetime risk.
Several inherited genetic syndromes are known to carry a higher risk of developing leukemia. Li-Fraumeni syndrome, for instance, is a rare disorder caused by an inherited mutation in the TP53 gene. Individuals with a mutated copy have an increased risk for various cancers, including sarcomas, brain tumors, breast cancer, and acute leukemias. The lifetime risk of cancer for people with Li-Fraumeni syndrome can be as high as 90% by age 60.
Down syndrome, or Trisomy 21, is another condition associated with a heightened leukemia risk. Children with Down syndrome have an extra copy of chromosome 21, increasing their likelihood of developing both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Other rare inherited conditions like Fanconi anemia and Neurofibromatosis type 1 also predispose individuals to leukemia.
Not everyone who inherits the mutation will develop cancer, a concept known as incomplete penetrance. The presence of the inherited mutation is often the “first hit,” and a second, acquired mutation in the other copy of the gene may be necessary for the cancer to develop. This highlights the interplay between inherited susceptibility and random genetic events.
Understanding Family History and Risk
Having a first-degree relative—defined as a parent, sibling, or child—with leukemia does slightly increase a person’s own risk. For chronic lymphocytic leukemia (CLL), for example, having a first-degree relative with the disease can increase one’s risk by two to four times. Since leukemia is a relatively rare disease, the absolute risk for most people remains very low.
The risk becomes more notable when multiple first-degree relatives are affected, or if a relative was diagnosed at an unusually young age. These patterns can suggest the presence of an underlying inherited genetic syndrome within the family. In such cases, genetic counseling and testing might be considered to identify a specific germline mutation.
For the vast majority of cases, leukemia is not passed from parent to child because most are caused by acquired mutations that are not heritable. The familial link is stronger for certain types of leukemia than others, and the risk increases with the number of affected close relatives.
Studies have analyzed large population databases to quantify this familial risk. A study in Sweden found that about 4.1% of all blood cancer diagnoses had a family link. The research confirmed that the risk was higher if the affected relative was a sibling or was diagnosed at a younger age. This data helps clinicians provide more precise risk assessments for concerned individuals.
Other Factors Contributing to Leukemia
Genetics are not the only factors that contribute to leukemia development. Certain environmental and lifestyle factors can increase the risk of developing the somatic mutations that lead to leukemia. These exposures do not cause leukemia directly but can damage the DNA in bone marrow cells, making mutations more likely to occur over time.
High doses of ionizing radiation are a well-established risk factor, observed in survivors of atomic bomb explosions and nuclear reactor accidents. Long-term exposure to certain industrial chemicals is also linked to an increased risk, with benzene being a primary example. Benzene is a solvent used in the manufacturing of plastics and rubbers, and workplace exposure has been associated with a higher incidence of acute myeloid leukemia (AML).
Previous cancer treatment is another factor. Certain chemotherapy drugs and radiation therapy, while effective at treating one cancer, can damage the DNA of blood-forming cells. This can lead to a secondary, or treatment-related, leukemia years later. Additionally, lifestyle choices like smoking are connected to a higher risk of AML, as cigarettes contain numerous chemicals, including benzene, that are known to cause cancer.