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Y Shimamoto, K Suga, K Shibata, M Matsuzaki, H Yano and M Yamaguchi
Department of Internal Medicine, Saga Medical School, Japan.
The proviral DNA of human T-cell lymphotrophic virus type I (HTLV-I) is
known to be integrated monoclonally in the malignant cells of adult T- cell
leukemia/lymphoma (ATL), which is a peripheral T-cell malignancy caused by
this virus. We studied the relationship between the integration patterns of
HTLV-I and clinical characteristics in 89 patients with ATL. The proviral
DNA of HTLV-I was examined by the standard Southern blot analysis using the
endonucleases EcoRI and Pst I. One clear band of greater than 9 kb was
detected in most of the patients (83 case) when cellular DNA was digested
with EcoRI. On the other hand, extraordinary integration patterns of HTLV-I
proviral DNA were detected in 6 patients; 3 of them showed two bands, while
the other 3 showed one band smaller than 9 kb. When cellular DNA was
digested with PstI, the band patterns of these patients were quite
different from those of typical patients. The patients with the
extraordinary integration patterns had clinical characteristics dissimilar
to those of the other 83 patients with the ordinary integration pattern.
The patients with two bands by EcoRI digestion always had severe hypoxemia
with extremely high levels of serum lactate dehydrogenase at first
presentation and showed peculiar organ infiltrations, such as retina and
muscle, which were less frequent in the other ordinary 83 patients. They
all died within 8 months after the onset. In contrast, the patients with
one smaller band by EcoRI digestion always had small and mature T
lymphocytes with bilobulated nuclei without lymphadenopathy and showed a
favorable clinical course, which was uncommon in the ordinary cases. They
were alive 20 to 38 months after diagnosis. Rearranged bands of the T-cell
receptor gene were detected in all patients with unusual integration. These
findings indicate that the integration patterns of HTLV-I proviral DNA have
a clinical implication and may be one of the explanations for heterogeneity
in the behavior of this disease.
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| Copyright © 1994 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||