title: How new advances in genetic analysis are influencing the understanding and treatment of childhood acute leukemia.
abstract: OBJECTIVE
  This review describes the recent advances in genomic profiling that have provided critical new insights into the biology of acute leukemia in children.
  
  
  RESULTS
  Acute leukemia genomes commonly harbor submicroscopic gains and deletions of DNA which target key cellular pathways that influence leukemogenesis and the likelihood of treatment failure, particularly in acute lymphoblastic leukemia (ALL). Notably, genetic alterations targeting transcriptional regulators of lymphoid development are a hallmark of B-progenitor ALL, and alteration of specific genes in this pathway, such as IKZF1 (encoding IKAROS), are associated with high-risk ALL. Integrated genomic profiling has identified potential therapeutic targets in ALL, including aberrant cytokine receptor signaling mediated by rearrangements and mutation of CRLF2 and JAK2. Genome-wide association studies are also providing important insights into the role of inherited genetic variation and susceptibility to ALL. In contrast, genomic profiling of acute myeloid leukemia (AML) has thus far yielded fewer insights, but ongoing resequencing of leukemia genomes is uncovering novel mutations in both ALL and AML.
  
  
  CONCLUSIONS
  Genomic profiling has identified important new genetic lesions that contribute to leukemogenesis. These findings will have important implications for the development of new diagnostic tests and treatment approaches in high-risk leukemia. Future studies will be increasingly reliant on comprehensive genomic sequencing to reveal the spectrum of genetic alterations in this disease, with the ultimate aim of improving the treatment outcome for leukemia patients.
authors.affiliation: Department of Pathology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Kathryn G
authors.initials: KG
authors.lastname: Roberts
authors.forename: Charles G
authors.initials: CG
authors.lastname: Mullighan
mesh_terms: D002648:Child; D020869:Gene Expression Profiling / Q000379:methods*; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D053614:Janus Kinase 2 / Q000235:genetics*; D009154:Mutation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000628:therapy*; D018121:Receptors, Cytokine / Q000235:genetics*
chemical_list: C498762:CRLF2 protein, human; C497239:IKZF1 protein, human; D018121:Receptors, Cytokine; D051740:Ikaros Transcription Factor; C507924:JAK2 protein, human; D053614:Janus Kinase 2