Acute Myeloid Leukemia (AML) is a fast-growing cancer originating in the bone marrow and blood, characterized by the rapid production of abnormal white blood cells called myeloid blasts. These cancerous cells build up, crowding out the space needed for healthy blood cell production. AML is an aggressive disease driven by genetic changes within blood-forming cells. A frequent question is whether these genetic changes mean the cancer is inherited and passed down through generations.
Distinguishing Inherited and Acquired AML
Over 90% of Acute Myeloid Leukemia cases are acquired, or sporadic, meaning they are not passed down from a parent. Acquired AML results from somatic mutations, which are genetic changes that occur in a single cell during a person’s lifetime. These somatic changes are only present in the cancerous cells and cannot be inherited by children.
Inherited AML is caused by germline mutations, which are present in the egg or sperm cell and passed from a parent to a child. These germline mutations are present in every cell of the body from birth and significantly increase a person’s lifetime risk of developing AML. While a person inherits a gene that increases their risk, they do not inherit the cancer itself, but rather a predisposition. The proportion of AML cases linked to inherited mutations is small, but their recognition is important for family screening and clinical management.
Specific Inherited Genetic Conditions
A small number of AML cases are linked to specific inherited genetic conditions and syndromes that predispose individuals to the disease. These conditions often involve defects in DNA repair, immune function, or blood cell development. A primary category includes inherited bone marrow failure syndromes, where the bone marrow fails to produce sufficient blood cells, creating an unstable environment conducive to leukemia.
Fanconi anemia and Shwachman-Diamond syndrome are examples of inherited bone marrow failure syndromes that increase the risk of AML. Dyskeratosis Congenita, characterized by abnormal maintenance of telomeres, is also associated with a high risk of developing myeloid malignancies.
Beyond these, specific familial leukemia syndromes are caused by inherited mutations in genes that regulate blood cell growth and maturation. Germline mutations in the RUNX1 gene cause familial platelet disorder with a propensity for developing AML. Another element is familial AML with mutated CEBPA, where an inherited change in the CEBPA gene significantly raises the risk of developing AML. Certain constitutional syndromes, such as Down syndrome, Neurofibromatosis Type 1, and Li-Fraumeni syndrome, also increase the likelihood of developing AML.
Non-Hereditary Risk Factors
Since most AML is acquired, identifying non-hereditary risk factors provides context for understanding the disease’s origin. These factors contribute to the development of sporadic AML by causing the somatic mutations that drive the cancer.
One established environmental exposure is the industrial chemical benzene, which is linked to an increased risk of developing acute leukemia. Benzene exposure occurs in certain workplaces, such as oil refineries and chemical plants, and is also a component of cigarette smoke.
High-dose exposure to ionizing radiation, such as from a nuclear accident or prior radiation therapy, is another risk factor for AML. The risk from radiation exposure depends on the dose received and the area of the body exposed.
A significant proportion of acquired AML is classified as treatment-related, or secondary AML, which arises following previous treatment for a different malignancy. This secondary AML is often associated with prior chemotherapy, particularly alkylating agents and topoisomerase inhibitors.
The strongest independent risk factor for AML is increasing age, with the median age of diagnosis being approximately 68 years.
Navigating Genetic Testing and Counseling
For individuals concerned about a potential family link to AML, genetic testing and counseling offer a structured way to assess risk. Genetic counseling should be considered by anyone with a strong family history of AML, especially if the cancer occurred at a young age or if multiple close relatives have been affected by myeloid cancers. A genetic counselor can analyze the family medical history and determine if the pattern suggests an inherited syndrome.
Genetic testing can be performed for known predisposition genes, such as RUNX1, CEBPA, and GATA2, using a blood or saliva sample. The process distinguishes between diagnostic testing, performed on an affected individual to identify a germline mutation, and predictive testing, offered to unaffected family members. If a germline mutation is identified, the counselor explains the specific level of increased risk, which is often expressed as a probability rather than a guarantee of developing the disease. This information is valuable for implementing surveillance strategies, such as regular blood tests, to detect the onset of AML early.