Acute Myeloid Leukemia (AML) is a fast-growing cancer that originates in the blood and bone marrow. This disease affects the myeloid line of blood cells, leading to the rapid accumulation of abnormal, immature cells called myeloblasts or leukemic blasts. These abnormal cells crowd out healthy blood cells, interfering with the body’s ability to produce red blood cells, white blood cells, and platelets. AML progresses quickly, and if left untreated, it can become life-threatening.
Understanding AML Origin
While the question of whether AML is hereditary is common, most cases are not directly inherited. Most AML cases, known as sporadic AML, arise from acquired genetic mutations during a person’s lifetime. These acquired mutations occur in the DNA of blood stem cells within the bone marrow, leading to uncontrolled cell growth and division.
A small percentage of AML cases are hereditary, resulting from an inherited genetic predisposition. This distinction between germline mutations (inherited) and somatic mutations (acquired) is important for understanding AML’s origins. Even when a genetic predisposition exists, it typically increases the likelihood of developing AML rather than guaranteeing it.
Inherited Genetic Predispositions
Inherited genetic syndromes and gene mutations increase the risk of hereditary AML. For example, individuals with Down syndrome have a higher predisposition to AML. Other conditions, such as Fanconi anemia, a bone marrow failure syndrome, significantly raise the risk.
Gene mutations in specific genes like CEBPA, RUNX1, GATA2, and DDX41 are also associated with an increased risk of familial AML. For instance, RUNX1 mutations can lead to familial platelet disorder with a propensity for myeloid malignancies. Similarly, GATA2 mutations are linked to bone marrow failure and myelodysplastic syndrome, which can progress to AML.
Acquired Risk Factors
Beyond inherited predispositions, several acquired risk factors contribute to the development of sporadic AML. Exposure to certain chemicals, such as benzene (found in gasoline and industrial solvents), has a known link to AML, with long-term exposure increasing the risk.
High doses of ionizing radiation, whether from therapeutic radiation for previous cancers or accidental exposures, are also recognized risk factors. Prior chemotherapy or radiation therapy for other cancers can also lead to therapy-related AML, a secondary form of the disease. Certain pre-existing blood disorders, including myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), can also transform into AML over time.
Navigating Genetic Risk
For individuals and families concerned about a potential hereditary risk for AML, genetic counseling provides guidance. Genetic counselors assess a comprehensive family medical history, spanning multiple generations, to identify patterns of disease. They then discuss the appropriateness of genetic testing, explaining the potential implications of results for the individual and their relatives.
Genetic testing for AML predisposition involves analyzing DNA for specific mutations or chromosomal changes. This process can help determine if an inherited variant is present, which may influence treatment strategies or surveillance plans. The insights gained can also be relevant for family planning decisions and for informing at-risk family members about their potential susceptibility.