Adult T cell leukaemia/lymphoma (ATL) arises from clonally expanded T cells that are infected with human T cell leukaemia virus type-1 (HTLV-1). Here, we show that ATL can be detected early in HTLV-1-carriers through quantification of T-cell receptor (TCR)Vβ subunit diversity on T-cells infected with HTLV-1 (CD3+ CCR4+ CD26− T-cells) using an ‘oligoclonality index’ (OCI-flow). We established a reference range for OCI-flow by analysing peripheral blood mononuclear cells (PBMCs) from HTLV-1-carriers who had not developed ATL in a median of 10.5 years follow up (n = 38) and patients with ATL (n = 30). In the third cohort of HTLV-1-carriers with no history or clinical evidence of ATL (n = 106), 19% of high proviral load (PVL, ≥4 copies of HTLV-1/100 PBMCs) carriers had an OCI-flow in the ATL range, >0.770. Carriers with an OCI-flow >0.770 (n = 14) had higher lymphocyte counts and PVLs and were more likely to have a family history of ATL than carriers with OCI-flow ≤0.770. ATL subsequently developed in two of these 14 carriers but no carriers with OCI-flow ≤0.770 (p = 0.03, cumulative follow-up 129 person-years). This method can be used to identify a subset of high-PVL HTLV-1-carriers at increased risk of developing ATL who may benefit from intervention therapy, prior to the detection of disease.
Purpose of reviewAdult T-cell leukemia-lymphoma (ATL) is an aggressive mature T-cell malignancy that arises in approximately 5% of carriers of human T-lymphotropic virus type 1 (HTLV-1), but this risk is not random among carriers. We describe recent advance in pathogenesis, risk factors and for early detection of ATL.
Recent findingsUnraveling ATL molecular genetics has shed light on pathogenesis and provides insights into novel therapeutic targets. Moreover, an important step in improving outcomes is identifying asymptomatic carriers who are at high risk of progression to ATL, which has traditionally relied on quantifying the proviral load (PVL). This can be done by quantifying oligoclonality-and in particular the expanded clone-with molecular and flow cytometric techniques, that can be applied to a clinical setting. Studies using these methods have shown that carriers with oligoclonal populations are at an increased risk of transformation, beyond that that predicted by PVL alone.
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