Gene Signature of High White Blood Cell Count in B-Precursor Acute Lymphoblastic Leukemia

PLoS One. 2016 Aug 18;11(8):e0161539. doi: 10.1371/journal.pone.0161539. eCollection 2016.

Abstract

In this study we sought to identify genetic factors associated with the presenting white blood cell (WBC) count in B-precursor acute lymphoblastic leukemia (BP-ALL). Using ETV6-RUNX1-positive BP-ALL patient samples, a homogeneous subtype, we identified 16 differentially expressed genes based on the presenting WBC count (< 50,000/cumm vs > 50,000). We further confirmed that IL1R1, BCAR3, KCNH2, PIR, and ZDHHC23 were differentially expressed in a larger cohort of ETV6-RUNX1-negative BP-ALL patient samples. Statistical analysis demonstrated that expression levels of these genes could accurately categorize high and low WBC count subjects using two independent patient sets, representing positive and negative ETV6-RUNX1 cases. Further studies in leukemia cell line models will better delineate the role of these genes in regulating the white blood cell count and potentially identify new therapeutic targets.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / physiology
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology
  • Child
  • Child, Preschool
  • Dioxygenases
  • ERG1 Potassium Channel / genetics
  • ERG1 Potassium Channel / physiology
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Genetic Markers / genetics
  • Guanine Nucleotide Exchange Factors
  • Humans
  • Leukocyte Count*
  • Male
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology
  • Oligonucleotide Array Sequence Analysis
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Protein Interaction Maps / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptors, Interleukin-1 Type I / genetics
  • Receptors, Interleukin-1 Type I / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • BCAR3 protein, human
  • Carrier Proteins
  • ERG1 Potassium Channel
  • Genetic Markers
  • Guanine Nucleotide Exchange Factors
  • IL1R1 protein, human
  • KCNH2 protein, human
  • Nuclear Proteins
  • Receptors, Interleukin-1 Type I
  • Dioxygenases
  • PIR protein, human