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Cancer Health Center

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Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - General Information About Childhood Acute Lymphoblastic Leukemia (ALL)


Down syndrome

Children with Down syndrome have an increased risk of developing both ALL and acute myeloid leukemia (AML),[14,15] with a cumulative risk of developing leukemia of approximately 2.1% by age 5 years and 2.7% by age 30 years.[14,15]

Approximately one-half to two-thirds of cases of acute leukemia in children with Down syndrome are ALL, and about 2% to 3% of childhood ALL cases occur in children with Down syndrome.[16,17,18] While the vast majority of cases of AML in children with Down syndrome occur before the age of 4 years (median age, 1 year),[19] ALL in children with Down syndrome has an age distribution similar to that of ALL in non-Down syndrome children, with a median age of 3 to 4 years.[16,17]

Patients with ALL and Down syndrome have a lower incidence of both favorable (t(12;21) and hyperdiploidy) and unfavorable (t(9;22) or t(4;11) and hypodiploidy) cytogenetic findings and a near absence of T-cell phenotype.[16,17,18,19] Approximately 50% to 60% of cases of ALL in children with Down syndrome have genomic alterations affecting CRLF2 that generally result in overexpression of this gene.[20,21,22]CRLF2 genomic alterations are observed at a much lower frequency (<10%) in children with B-precursor ALL who do not have Down syndrome.[22,23,24] It does not appear that genomic CRLF2 aberrations in patients with Down syndrome and ALL have prognostic relevance.[21] However, IKZF1 gene deletions, observed in up to 35% of patients with Down syndrome and ALL, have been associated with a significantly worse outcome in this group of patients.[21]

Approximately 20% of ALL cases arising in children with Down syndrome have somatically acquired JAK2 mutations,[20,21,25,26,27] a finding that is uncommon among younger children with ALL but that is observed in a subset of primarily older children and adolescents with high-risk B-precursor ALL.[28] Almost all Down syndrome ALL cases with JAK2 mutations also have CRLF2 genomic alterations.[20,21,22] Preliminary evidence suggests no correlation between JAK2 mutation status and 5-year event-free survival in children with Down syndrome and ALL,[21,26] but more study is needed to address this issue and the prognostic significance of IKZF1 gene deletions.

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