title: Updates in the biology and therapy for infant acute lymphoblastic leukemia.
abstract: The prognosis for infants less than 12 months of age who are diagnosed with acute lymphoblastic leukemia (ALL) remains poor despite overall advances in the treatment of childhood ALL. In this review, we highlight the recent advances in the understanding of the pathogenesis of infant ALL and discuss opportunities for translating these findings into clinical trials.
  
  
  
  Infant ALL can be divided into two major disease types, defined by the presence or absence of KMT2A (MLL) rearrangement (KMT2A-R). Recent molecular profiling studies have found that infant ALL with KMT2A-R is an epigenomic disease that lacks other somatic driver mutations. Strategies to intensify therapy have not improved survival for infants with KMT2A-R ALL. In contrast, infant ALL without KMT2A-R is more similar to ALL of older children and survival has improved modestly with intensification of chemotherapy. Discovery of clonal molecular markers that predict chemoresistance will allow further risk classification and development of novel treatment strategies. Modern clinical trials are integrating molecularly targeted therapies into the treatment of infant ALL.
  
  
  
  Advances in molecular profiling and integration of targeted therapy have the potential to reduce toxicity and improve survival for infants with ALL.
authors.affiliation: aDepartment of Pediatrics, Division of Hematology/Oncology/Bone Marrow Transplantation, Children's Mercy Hospital and Clinics, Kansas City, Missouri, USA bPrincess Máxima Center for Paediatric Oncology, Utrecht, The Netherlands.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Guest
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Stam
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D003131:Combined Modality Therapy; D044127:Epigenesis, Genetic; D005820:Genetic Testing; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D058990:Molecular Targeted Therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor