High-throughput sequencing of archival cerebrospinal fluid specimens defines B-lymphoblastic leukemia clonal composition

Pediatr Blood Cancer. 2024 Nov;71(11):e31281. doi: 10.1002/pbc.31281. Epub 2024 Aug 21.

Abstract

Detailed characterization of the B-lymphoblastic leukemia (B-ALL) cells which invade the central nervous system (CNS) has been limited by practical challenges. To test whether the clonal composition of the cerebrospinal fluid (CSF) reflects the primary B-ALL tissue, we applied immunoglobulin (Ig) high-throughput sequencing (HTS) of archival CSF cytospin preparations from six patients with morphologically defined CNS involvement. We discovered that most CSF clones are detectable at some timepoint in the primary tissue, but that shifting clonal abundance is prevalent across tissue sites between diagnosis and relapse. Ig HTS of CSF cytospins may improve understanding of sanctuary site dissemination in B-ALL.

Keywords: B‐lymphoblastic leukemia; CNS involvement; CSF surveillance; clonal composition; immunoglobulin high‐throughput sequencing; pediatric oncology; relapse prediction; response assessment.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Female
  • High-Throughput Nucleotide Sequencing* / methods
  • Humans
  • Infant
  • Male
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / cerebrospinal fluid
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology