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

Holly Edwards,Ana C Xavier,Roland Chu,Jeffrey W Taub,Melody Neely,Larry H Matherly,Mara Rubenstein,J Timothy Caldwell,Ryan Thummel,Yubin Ge,Alan A Dombkowski,Obul Reddy Bandapalli

doi:10.1371/journal.pone.0161539

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.

Highlights

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer
Using ETV6RUNX1-positive B-precursor acute lymphoblastic leukemia (BP-ALL) patient samples, a homogeneous subtype, we identified 16 differentially expressed genes based on the presenting white blood cell (WBC) count (< 50,000/cumm vs > 50,000)
Principal component analysis revealed sample clustering based on the combined profiles of these features, with high WBC samples clustering on the right and low WBC on the left (Fig 1b). These results demonstrated that the samples could be separated by the WBC (x103/cumm)

Summary

Introduction

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Over the last 30 years, the 5-year survival rate has significantly improved, increasing from 57% to 90% [1]. Using ETV6RUNX1-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.

Results

Conclusion