Advanced human T‐cell leukemia virus type 1 carriers and early‐stage indolent adult T‐cell leukemia‐lymphoma are indistinguishable based on CADM1 positivity in flow cytometry

Abstract

We previously reported that the cell adhesion molecule 1 (CADM1) versus CD7 plot in flow cytometry reflects disease progression in human T-cell leukemia virus type 1 (HTLV-1) infection. In CD4+ cells from peripheral blood, CADM1−CD7+ (P), CADM1+CD7dim (D) and CADM1+CD7− (N) subpopulations are observed. The D and N subpopulations increase as asymptomatic HTLV-1 carriers (AC) progress to indolent adult T-cell leukemia-lymphoma (ATL) and the N subpopulation then expands in aggressive ATL. In the present study we examined whether the analysis can estimate the risk of developing ATL in advanced AC. Peripheral blood samples from AC (N = 41) and indolent ATL patients (N = 19) were analyzed by flow cytometry using the CADM1 versus CD7 plot for CD4+ cells and inverse long PCR (clonality analysis) of FACS-sorted subpopulations. Almost all AC with a high HTLV-1 proviral load (>4 copies/100 cells) had a CADM1+ (D + N) frequency of >10%. AC with 25% < CADM1+ ≤ 50% contained expanded clones similar to smoldering-type ATL. In many patients in the 25% < CADM1+ ≤ 50% group, the proportion of abnormal lymphocytes was distributed around the 5% line, which divides AC and smoldering-type ATL in Shimoyama's classification. In conclusion, the CADM1 versus CD7 plot is useful for selection of putative high-risk AC. The characteristics of some AC and smoldering ATL are said to be similar; however, long-term follow up is required and the clinical outcome (e.g. rate of transformation) of these cases should be used to determine whether to include them in the same clinical category.

Epidemiological and clinical features of adult T‐cell leukemia–lymphoma in Japan, 2010–2011: A nationwide survey

“…For the elderly patients, the development of new, less toxic agents such as mAbs or small molecule agents, rather than intensive cytotoxic therapies, are urgently needed. Furthermore, any strategies for preventing the development of ATL in HTLV‐1 carriers by identifying definite markers for high‐risk HTLV‐1 carriers using, for example, multicolor flow cytometry is also needed …”

“…Furthermore, any strategies for preventing the development of ATL in HTLV-1 carriers by identifying definite markers for high-risk HTLV-1 carriers using, for example, multicolor flow cytometry is also needed. (33)…”

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

“…We recently took advantage of the universal expression of CADM1 in HTLV‐1‐infected cells and the downregulation of CD7 expression based on the oncogenic stage of HTLV‐1‐infected cells to develop a flow cytometric system using CADM1 versus CD7 plotting of CD4 + cells (named the HTLV‐1 analysis system by flow cytometry [HAS‐Flow]). We previously reported that HAS‐Flow enables an objective evaluation of the clinical disease progression of AC and indolent ATL cases …”

Effector Regulatory T Cells Reflect the Equilibrium between Antitumor Immunity and Autoimmunity in Adult T-cell Leukemia

“…ATL cells often share the Treg phenotype, i.e., CD3 þ CD4 þ CD25 þ Foxp3 þ (8,9). Although ATL cells may be defined by their expression of CADM1 (10,11), the overlap and differences between Tregs and ATL cells remain unclear.…”