title: Biology, risk stratification, and therapy of pediatric acute leukemias: an update.
abstract: OBJECTIVE
  We review recent advances in the biologic understanding and treatment of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), identify therapeutically challenging subgroups, and suggest future directions of research.
  
  
  METHODS
  A review of English literature on childhood acute leukemias from the past 5 years was performed.
  
  
  RESULTS
  Contemporary treatments have resulted in 5-year event-free survival rates of approximately 80% for childhood ALL and almost 60% for pediatric AML. The advent of high-resolution genome-wide analyses has provided new insights into leukemogenesis and identified many novel subtypes of leukemia. Virtually all ALL and the vast majority of AML cases can be classified according to specific genetic abnormalities. Cooperative mutations involved in cell differentiation, cell cycle regulation, tumor suppression, drug responsiveness, and apoptosis have also been identified in many cases. The development of new formulations of existing drugs, molecularly targeted therapy, and immunotherapies promises to further advance the cure rates and improve quality of life of patients.
  
  
  CONCLUSIONS
  The application of new high-throughput sequencing techniques to define the complete DNA sequence of leukemia and host normal cells and the development of new agents targeted to leukemogenic pathways promise to further improve outcome in the coming decade.
authors.affiliation: St Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, USA. ching-hon.pui@stjude.org
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.forename: William L
authors.initials: WL
authors.lastname: Carroll
authors.forename: Soheil
authors.initials: S
authors.lastname: Meshinchi
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Arceci
mesh_terms: D002648:Child; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics / Q000628:therapy*; D009154:Mutation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000628:therapy*; D012008:Recurrence; D014158:Transcription, Genetic