A comprehensive assessment using multiple factors based on HAS-Flow analysis predicts ATL development and progression

Adult T-cell leukemia/lymphoma develops decades after Human T-lymphotropic virus type 1 (HTLV-1) infection. Factors like proviral load (PVL), soluble interleukin-2 receptors (sIL-2R), and clonality are associated with its pathogenesis. However, a comprehensive assessment using multiple factors of ATL development and progression based on flow cytometry (HAS-Flow) has not been performed. We conducted a 10-year clinical follow-up of 160 asymptomatic people living with HTLV-1 using HAS-Flow, PVL, sIL-2R, and the HTLV-1 integration site identification. The cases were classified into three groups based on cell adhesion molecule 1 (CADM1)-expressing cells by HAS-Flow: Group 1 (≤ 10%, 115 cases), Group 2 (> 10% to ≤ 25%, 33 cases), and Group 3 (> 25%, 12 cases). In the follow-up, no cases in Group 1 developed ATL, while five cases in Group 2 and nine in Group 3 did. Among the developed ATL, one case in Group 2 and six in Group 3 progressed to aggressive ATL. Higher CADM1-expressing cells and sIL-2R levels were linked to earlier ATL development. The HTLV-1 integration site was identified in all aggressive ATL cases. Thus, evaluating CADM1-expressing cells by HAS-Flow, assessing sIL-2R, and identifying the HTLV-1 integration site can better predict ATL development and progression to aggressive ATL.