Feasibility of monitoring peripheral blood to detect emerging clones in children with acute lymphoblastic leukemia

Pediatr Blood Cancer. 2020 Jul;67(7):e28306. doi: 10.1002/pbc.28306. Epub 2020 May 11.

Abstract

Relapse-enriched somatic variants drive drug resistance in childhood acute lymphoblastic leukemia. We used digital droplet-based polymerase chain reaction to establish whether relapse-enriched mutations in emerging subclones could be detected in peripheral blood samples before frank relapse. Although limitations in sensitivity for some probes hindered detection of certain variants, we successfully detected variants in NT5C2 and PRPS1 at a fractional abundance of 0.005% to 0.3%, 41 to 116 days before relapse. As mutations in both these genes confer resistance to thiopurines, early detection protocols using peripheral blood could be implemented to preemptively alter maintenance therapy to extinguish resistant clones before overt relapse.

Keywords: backtracking; clonal evolution; ddPCR; relapsed acute lymphoblastic leukemia; thiopurines.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Case-Control Studies
  • Child
  • Clone Cells / metabolism
  • Clone Cells / pathology*
  • Combined Modality Therapy
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Mutation*
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Recurrence, Local / therapy
  • Polymerase Chain Reaction
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Prognosis

Substances

  • Biomarkers, Tumor