Detection of minimal residual disease in B lymphoblastic leukemia using viSNE

Cytometry B Clin Cytom. 2015 Sep-Oct;88(5):294-304. doi: 10.1002/cyto.b.21252. Epub 2015 Jun 2.

Abstract

Background: Minimal residual disease (MRD) following treatment is a robust prognostic marker in B lymphoblastic leukemia. However, the detection of MRD by flow cytometric immunophenotyping is technically challenging, and an automated method to detect MRD is therefore desirable. viSNE, a recently developed computational tool based on the t-Distributed Stochastic Neighbor Embedding (t-SNE) algorithm, has been shown to be capable of detecting synthetic "MRD-like" populations of leukemic cells created in vitro, but whether viSNE can facilitate the immunophenotypic detection of MRD in clinical samples has not been evaluated.

Methods: We applied viSNE retrospectively to 8-color flow cytometric immunophenotyping data from normal bone marrow samples, and samples from B lymphoblastic leukemia patients with or without suspected MRD on the basis of conventional manual gating.

Results: In each of 14 bone marrow specimens containing MRD or suspected MRD, viSNE identified a putative MRD population; an abnormal composite immunophenotype was confirmed for the putative MRD in each case. MRD populations were not identified by viSNE in control bone marrow samples from patients with increased normal B-cell precursors, or in post-treatment samples from B lymphoblastic leukemia patients who did not have detectable MRD by manual gating.

Conclusion: viSNE shows promise as an automated method to facilitate immunophenotypic MRD detection in patients treated for B lymphoblastic leukemia.

Keywords: ALL; B lymphoblastic leukemia; flow cytometry; minimal residual disease; viSNE.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms*
  • Automation, Laboratory
  • Biomarkers, Tumor / analysis*
  • Bone Marrow Examination / methods*
  • Flow Cytometry / methods*
  • Humans
  • Immunophenotyping / methods*
  • Leukemia, B-Cell / chemically induced*
  • Leukemia, B-Cell / immunology
  • Leukemia, B-Cell / pathology
  • Leukemia, B-Cell / therapy
  • Neoplasm, Residual
  • Predictive Value of Tests
  • Retrospective Studies
  • Signal Processing, Computer-Assisted*
  • Stochastic Processes
  • Treatment Outcome

Substances

  • Biomarkers, Tumor