title: Gene Signature of High White Blood Cell Count in B-Precursor Acute Lymphoblastic Leukemia.
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.
authors.affiliation: Department of Oncology, Wayne State University School of Medicine, Detroit, MI, United States of America.|Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, United States of America.
authors.forename: Holly
authors.initials: H
authors.lastname: Edwards
authors.affiliation: Division of Pediatric Hematology/Oncology, Children's Hospital of Michigan, Detroit, MI, United States of America.
authors.forename: Mara
authors.initials: M
authors.lastname: Rubenstein
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Children's Hospital of Michigan, Detroit, Michigan, United States of America.|Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, United States of America.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Dombkowski
authors.affiliation: MD/PhD Program, Wayne State University School of Medicine, Detroit, MI, United States of America.|Cancer Biology Program, Wayne State University School of Medicine, Detroit, MI, United States of America.
authors.forename: J Timothy
authors.initials: JT
authors.lastname: Caldwell
authors.affiliation: Division of Pediatric Hematology/Oncology, Children's Hospital of Michigan, Detroit, MI, United States of America.|Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, United States of America.
authors.forename: Roland
authors.initials: R
authors.lastname: Chu
authors.affiliation: Division of Pediatric Hematology/Oncology, Children's Hospital of Alabama, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Xavier
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI, United States of America.
authors.forename: Ryan
authors.initials: R
authors.lastname: Thummel
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI, United States of America.
authors.forename: Melody
authors.initials: M
authors.lastname: Neely
authors.affiliation: Department of Oncology, Wayne State University School of Medicine, Detroit, MI, United States of America.|Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, United States of America.|Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United States of America.
authors.forename: Larry H
authors.initials: LH
authors.lastname: Matherly
authors.affiliation: Department of Oncology, Wayne State University School of Medicine, Detroit, MI, United States of America.|Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, United States of America.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, United States of America.|Division of Pediatric Hematology/Oncology, Children's Hospital of Michigan, Detroit, MI, United States of America.|Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, United States of America.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Taub
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D049308:Dioxygenases; D000072237:ERG1 Potassium Channel / Q000235:genetics / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000276:immunology; D060066:Protein Interaction Maps / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C118588:BCAR3 protein, human; D002352:Carrier Proteins; D000072237:ERG1 Potassium Channel; D005819:Genetic Markers; D020662:Guanine Nucleotide Exchange Factors; C508590:IL1R1 protein, human; C000606913:KCNH2 protein, human; D009687:Nuclear Proteins; D053573:Receptors, Interleukin-1 Type I; D049308:Dioxygenases; C105340:PIR protein, human