Adult T Cell Leukaemia ATL

It is now established that HTLV-1 is associated with ATL, HTLV-l-associated myelopathy or tropical spastic paraparesis (HAM/TSP) and uveitis. Other diseases such as chronic lung disease, monoclonal gammopathy, chronic renal failure, strongyloidiasis and nonspecific dermato-mycosis are also suggested to associate with the viral infection; however, further systematic studies are required to establish the exact relationships. Here, only ATL is described.

The Leukaemic Cells

ATL cells are T cells with the CD4+ phenotype and, usually, a highly lobulated nucleus. These cells always carry HTLV-1 proviruse(s) and the site of integration is monoclonal in a given ATL patient. In 70-80% of cases of ATL patients examined, one copy of the complete provirus was integrated into each leukaemic cell. Occasionally, one or two copies of defective provirus are integrated into the DNA of a single cell. Even in the defective genomes, preservation of the pX region in defective proviruses suggests its importance in tumorigenesis.

The leukaemic cells express a high level of IL-2Ra on their surfaces. Production of PTHrP, IL-1^ or GM-CSF by tumour cells has also been described. In almost all cases, leukaemic cells carry aberrant chromosomes, and there are frequently multiple abnormalities, such as trisomy of chromosome 7 and 14q11, 14q32 and 6/q15 translocations. The abnormality involving 14q32 was found in 25% of ATL patients, but the others appeared less frequently.

Clinical Features

ATL (Uchiyama et al., 1977) is classified into three phases, smouldering, chronic and acute phases, depending on clinical features. In smouldering ATL, patients commonly have from one to several per cent of morphologically abnormal T cells in their peripheral blood, but do not show other signs of severe illness and are therefore thought to be in an early stage of ATL development. In smouldering ATL, the abnormal cells are not aggressively malignant, but are HTLV-1 infected and expanded clon-ally. The onset of ATL is observed between 20 and 70 years of age, the peak rate of onset being in the 40s and 50s. The male-to-female ratio of ATL is 1.4:1.0. Symptoms of ATL vary from patient to patient, but are frequently complicated by skin lesions, enlargement of lymph nodes, liver and/or spleen and infiltration of leukaemic cells into the lungs and other organs. Patients usually have antibodies to HTLV-1 proteins, show an increased level of serum LDH and suffer from hypercalcaemia. The acute form, or phase, of ATL is aggressive and resistant to treatment; consequently, most patients in this phase die within 6 months of its onset.

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