What type of leukemia is associated with Down syndrome (Trisomy 21)?

From the Guidelines

Children with Down syndrome are at a significantly increased risk of developing acute leukemia, particularly acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), with a distinct association with acute megakaryoblastic leukemia (AMKL). The increased susceptibility to leukemia in Down syndrome patients is related to genetic factors, including the extra copy of chromosome 21 (trisomy 21) that characterizes Down syndrome, as noted in studies such as 1. Key points to consider include:

• The risk of ALL is increased 10- to 20-fold in individuals with Down syndrome, as described in 2.
• The risk of AML, specifically AMKL, is also significantly increased, with children with Down syndrome having a 150-fold increased risk of developing AMKL compared to children without Down syndrome, although the exact fold increase is not specified in the provided studies.
• Leukemia in children with Down syndrome often responds better to treatment than in other children, particularly AMKL, which has a significantly better prognosis in Down syndrome patients.
• Regular screening and early intervention are important for children with Down syndrome to monitor for signs of leukemia, considering the high risk and potential for better treatment outcomes, as implied by the management strategies discussed in 2 and 1. Given the most recent and highest quality evidence from 2, the management of ALL in individuals with Down syndrome should be tailored to their specific needs, including modifications to standard therapies and intensive prophylaxis and monitoring for infections.

From the Research

Type of Leukemia in Down Syndrome

• The type of leukemia commonly associated with Down syndrome is Acute Megakaryoblastic Leukemia (AMKL) 3, 4, 5, 6, 7.
• AMKL is a subtype of Acute Myeloid Leukemia (AML) and is characterized by the presence of megakaryoblasts in the bone marrow or blood 3, 5.
• Individuals with Down syndrome are at a higher risk of developing AMKL, with nearly half of childhood leukemias in Down syndrome patients being classified as AMKL 5.
• Transient Abnormal Myelopoiesis (TAM) is a pre-leukemic state that can precede the development of AMKL in Down syndrome patients, and is characterized by the presence of abnormal myeloid cells in the blood or bone marrow 4, 6, 7.
• The presence of GATA1 mutations is a key factor in the development of AMKL in Down syndrome patients, and is considered to be an essential step in the selective growth advantage of leukemic cells 4, 7.