Preleukemic state of adult T cell leukemia: abnormal T lymphocytosis induced by human adult T cell leukemia-lymphoma virus

Abstract

We report the clinical, hematologic, and immunologic features of 18 preleukemic adult T cell leukemia (pre-ATL) cases with abnormal T lymphocytosis induced by human adult T cell leukemia-lymphoma virus (HTLV/ATLV). The patients were from the Nagasaki district, which is one of the most endemic areas of ATL in Japan. Pre-ATL is a subclinical T cell abnormality differing from ATL. It is characterized by an insidious onset and appearance of abnormal T lymphocytes (10% to 40%) in the peripheral blood without clinical symptoms except for a few cases transiently presenting fever, skin eruptions, and slight lymphadenopathies. Most abnormal T lymphocytes were small and mature with incised or lobulated nuclei and formed E rosettes with sheep RBCs. Virologic and biomolecular analysis revealed that all cases were infected with HTLV, and proviral DNA was integrated in host lymphocytes from 12 of the 14 cases examined. Furthermore, the lymphocyte populations, including abnormal T lymphocytes, were monoclonal with respect to the site of the provirus integration. Abnormal T lymphocytosis persisted from one to more than seven years in six cases, three of which developed ATL after a one- to five-year pre-ATL stage, whereas abnormal T lymphocytes spontaneously decreased in the other seven patients. However, HTLV-infected monoclonal lymphocytes were detected in four cases examined, even after most of the abnormal T lymphocytes had disappeared. Moreover, the same clonally provirus- integrated lymphocytes persisted in two of four cases not only during the course of abnormal lymphocytosis, but also in the subsequent almost- normal blood. These results indicate that the majority of the cases were in a pre-ATL state with a potential to develop ATL.

Low prevalence of flower cells in U.S.A. blood donors infected with human T‐lymphotrophic virus types I and II

“…In ATL patients with leukaemia, flower cells are usually monoclonally infected with HTLV-I (Kinoshita et al, 1985;Chen et al, 1995). The prevalence of abnormal lymphocytes with flower cell features (at a frequency of 1% or less of white blood cells) in asymptomatic, healthy, HTLV-I-positive Japanese subjects has been reported as high as 43-47% (Kinoshita et al, 1985;Yamaguchi et al, 1988;Tachibana et al, 1992). Tachibana et al (1992) reported a correlation between the presence of flower cells and high proviral load among asymptomatic subjects.…”

Predictors of level of circulating abnormal lymphocytes among human T-lymphotropic virus type I carriers in Japan

“…The Ably level in peripheral blood smears is used in clinical practice to monitor smoldering ATL for the onset of overt leukemia. In a prospective study of HTLV-I carriers with high levels of Ably and symptoms of immune suppression, 3 of the 18 who were followed developed ATL in 5 years (Kinoshita et al, 1985). In another prospective observation, one of the 14 HTLV-I carriers with variable level of Ably developed ATL after 2 years of follow-up (Yamaguchi et al, 1988).…”

“…These observations have led to the hypothesis that the presence of Ably in HTLV-I carriers with clinical manifestations of immune suppression may predict the subsequent development of ATL. However, it is also known that Ably spontaneously disappears, while monoclonal integration of the provirus in lymphocytes continues (Kinoshita et al, 1985). It is uncertain what Ably represents with regard to pathogenesis, and the validity of low levels of Ably as a marker for the risk of ATL among asymptomatic HTLV-I carriers remains inconclusive.…”

“…It is not clear whether the Ably are in fact HTLV-I-infected T-lymphocytes or non-infected reactive cells. That Ably disappeared from the peripheral blood of a smoldering leukemia patient over a 5-year period (Kinoshita et al, 1985) challenges interpretation of Ably level as a correlate of the number of ''pre-leukemic'' cells or a direct indicator for risk of malignancy. The fact that some ATL are of the lymphoma type, in which few circulating leukemia cells are seen, also challenges the interpretation of Ably.…”

A polyclonal CD4+ and CD8+ lymphocytosis in a patient doubly infected with HTLV‐I and HIV‐1: A clinical and molecular analysis

“…DNA sequences. HTLV-I has been associated .with a syndrome termed In September 1984, the patient's constitutional symppre-ATL (adult T-cell leukemia/lymphoma) [29], which toms persisted, and he was found to have diffuse lymphis considered to be benign; but based on the monoclo-adenopathy. Six weeks later, nasopharyngeal lymphoid nality of the infected T-cell pclpulation, it might more enlargement and numerous 1-2-cm pulmonary nodules accurately be termed a low-grade malignancy [ 5 ] .…”