*4.2.5 Down syndrome ALL*

Children with Down syndrome (DS) have an increased predisposition compared to non-DS children to develop ALL with a cumulative risk of approximately 2.1% by age of 5 years and 2.7% by age of 30 [118, 119]. Children with DS constitute a very special group of pediatric ALL characterized by predominantly B immunophenotype and a marked absence of T immunophenotype. This group is neither associated with the favorable nor the unfavorable cytogenetic abnormalities as seen in common pediatric ALL [120]. *IKZF1* gene deletion, seen in approximately 35% of DS ALL portends inferior outcome [121, 122]. About 50–60% of the children with DS ALL harbor *CRLF2* mutation, much higher than in children with ALL without DS (<10%). Approximately, 20% of children with DS ALL also carry *JAK2* mutations, with majority also harboring *CRLF2* mutation. However, their prognostic significance is unknown [121, 123, 124].
