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

• Published in: PloS one 2016-08, Vol.11 (8), p.e0161539
• Main Authors: Edwards, Holly, Rubenstein, Mara, Dombkowski, Alan A, Caldwell, J Timothy, Chu, Roland, Xavier, Ana C, Thummel, Ryan, Neely, Melody, Matherly, Larry H, Ge, Yubin, Taub, Jeffrey W
• Format: Article
• Language: English
• Subjects: Acute lymphoblastic leukemia; Acute lymphocytic leukemia; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - physiology; Analysis; Biology; Biology and Life Sciences; Blood; Bone marrow; Breast cancer; Carrier Proteins - genetics; Carrier Proteins - physiology; Cell adhesion & migration; Cell culture; Child; Child, Preschool; Dioxygenases; ERG1 Potassium Channel - genetics; ERG1 Potassium Channel - physiology; Estrogens; Female; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Genes; Genetic aspects; Genetic factors; Genetic Markers - genetics; Guanine Nucleotide Exchange Factors; Hematology; Hormone replacement therapy; Humans; Immunology; Interleukin 1; Leukemia; Leukocyte Count; Leukocytes; Lymphatic leukemia; Lymphocytes B; Male; Medical prognosis; Medicine; Medicine and Health Sciences; Nuclear Proteins - genetics; Nuclear Proteins - physiology; Oligonucleotide Array Sequence Analysis; Oncology; Patients; Pediatrics; People and Places; Pneumoviridae; Potassium; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - immunology; Precursors; Principal components analysis; Protein Interaction Maps - genetics; Real-Time Polymerase Chain Reaction; Receptors, Interleukin-1 Type I - genetics; Receptors, Interleukin-1 Type I - physiology; Research and analysis methods; Runx1 protein; Statistical analysis; Statistical methods; Target recognition; White blood cell count
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0161539

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.