What is the role of genetics in the etiology of pediatric acute myelocytic leukemia (AML)?

Updated: Sep 12, 2017
  • Author: Mark E Weinblatt, MD; Chief Editor: Jennifer Reikes Willert, MD  more...
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Children with Down syndrome (trisomy 21) have a 15-fold increased risk of developing leukemia, most commonly acute megakaryoblastic leukemia, compared with the general population. The risk of megakaryoblastic leukemia in Down syndrome is approximately 400 times greater than it is in the rest of the population. Children with Down syndrome who have transient myeloproliferative syndrome as neonates, a condition often indistinguishable from acute leukemia, also have a high risk of developing acute leukemia in subsequent years.

Patients with inherited disorders, such as Shwachman-Diamond syndrome, Bloom syndrome, Diamond-Blackfan anemia, Fanconi anemia, dyskeratosis congenita, and Kostmann syndrome, also have an elevated risk of developing leukemia. Although statistics vary, about 10% of patients with Fanconi anemia, 5-10% of patients with Shwachman-Diamond syndrome, and 1 in 6 patients with Bloom syndrome develop leukemia. The risk of acute myeloid leukemia in patients with dyskeratosis congenita is nearly 200 times that of the normal population. These syndromes share features of poor DNA repair that are believed to predispose affected individuals to leukemogenic stimuli.

Children with neurofibromatosis type I also appear to be at increased risk for developing acute myeloid leukemia.

Although most cases are diagnosed after a relatively brief duration of symptoms, some patients may present with myelodysplasia. This relatively indolent disorder is characterized by slowly progressive anemia or thrombocytopenia. This disorder can be present for many months or even years before it ultimately converts to acute myeloid leukemia.

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