The role of CDKN2A/B deletions in pediatric acute lymphoblastic leukemia

Pediatr Hematol Oncol. 2016 Oct-Nov;33(7-8):415-422. doi: 10.1080/08880018.2016.1251518.

Abstract

The CDKN2A/B genes in the 9p21 chromosomal region are frequently involved in human cancer, including pediatric acute lymphoblastic leukemia (ALL). These genes encode 3 proteins that belong to the RB1 and TP53 pathways and act as tumor suppressors by regulating the G1/S checkpoint of the cell cycle. The prognostic value of deletions in the CDKN2A/B locus in ALL is controversial in part due to the limitations of the methodologies used. Further studies with advanced technologies are needed for elucidation. Future studies would also highlight whether CDK4/CDK6 selective inhibitors might be useful therapies for children with these genetic aberrations.

Keywords: CDK4/CDK6 inhibitors; CDKN2A gene; CDKN2B gene; deletions; pediatric acute lymphoblastic leukemia; prognosis.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 9 / genetics
  • Chromosomes, Human, Pair 9 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p15* / genetics
  • Cyclin-Dependent Kinase Inhibitor p15* / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18* / genetics
  • Cyclin-Dependent Kinase Inhibitor p18* / metabolism
  • Female
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • G1 Phase Cell Cycle Checkpoints / genetics
  • Gene Deletion*
  • Genetic Loci*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / pathology
  • Retinoblastoma Binding Proteins / genetics
  • Retinoblastoma Binding Proteins / metabolism
  • S Phase Cell Cycle Checkpoints / drug effects
  • S Phase Cell Cycle Checkpoints / genetics
  • Signal Transduction / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • CDKN2A protein, human
  • CDKN2B protein, human
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18
  • RB1 protein, human
  • Retinoblastoma Binding Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Ubiquitin-Protein Ligases