CD4+ CADM1+ cell percentage predicts disease progression in HTLV-1 carriers and indolent adult T-cell leukemia/lymphoma

Cancer Sci. 2019 Dec;110(12):3746-3753. doi: 10.1111/cas.14219.

Abstract

We recently took advantage of the universal expression of cell adhesion molecule 1 (CADM1) by CD4+ cells infected with HTLV-1 and the downregulation of CD7 expression that corresponds with the oncogenic stage of HTLV-1-infected cells to develop a flow cytometric system using CADM1 versus CD7 plotting of CD4+ cells. We risk-stratified HTLV-1 asymptomatic carriers (AC) and indolent adult T-cell leukemia/lymphoma (ATL) cases based on the CADM1+ percentage, in which HTLV-1-infected clones are efficiently enriched. AC and indolent ATL cases were initially classified according to their CADM1+ cell percentage. Follow-up clinical and flow cytometric data were obtained for 71 cases. In G1 (CADM1+ ≤ 10%) and G2 (10% < CADM1+ ≤ 25%) cases, no apparent clinical disease progression was observed. In G3 (25% < CADM1+ ≤ 50%) cases, five out of nine (55.5%) cases progressed from AC to smoldering-type ATL. In G4 (50% < CADM1+ ) cases, the cumulative incidence of receiving systemic chemotherapy at 3 years was 28.4%. Our results indicate that the percentage of the CD4+ CADM1+ population predicts clinical disease progression: G1 and G2 cases, including AC cases, are stable and considered to be at low risk; G3 cases, including advanced AC cases and smoldering-type ATL cases based on the Shimoyama criteria, are considered to have intermediate risk; and G4 cases, which are mainly indolent ATL cases, are unstable and at high risk of acute transformation.

Keywords: ATL; CADM1; HTLV-1; asymptomatic carriers; flow cytometry.

MeSH terms

  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / immunology*
  • Carrier State / immunology*
  • Cell Adhesion Molecule-1 / analysis*
  • Disease Progression
  • Female
  • HTLV-I Infections / drug therapy
  • HTLV-I Infections / immunology*
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / drug therapy
  • Leukemia-Lymphoma, Adult T-Cell / immunology*
  • Male
  • Middle Aged

Substances

  • CADM1 protein, human
  • Cell Adhesion Molecule-1