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Blood, 15 August 2001, Vol. 98, No. 4, pp. 1160-1165
NEOPLASIA
Expression of functional lung resistance-related protein
predicts poor outcome in adult T-cell leukemia
Nobuhito Ohno,
Ayako Tani,
Kimiharu Uozumi,
Shuichi Hanada,
Tatsuhiko Furukawa,
Suminori Akiba,
Tomoyuki Sumizawa,
Atae Utsunomiya,
Terukatsu Arima, and
Shin-ichi Akiyama
From the Department of Cancer Chemotherapy, Institute
for Cancer Research; the Second Department of Internal Medicine; and
the Department of Public Health, Faculty of Medicine, Kagoshima
University, Kagoshima, Japan.
Chemotherapy of patients with adult T-cell leukemia (ATL) has been
unsuccessful. The poor outcome is thought to be caused mainly by the
drug resistance of ATL cells. Lung resistance-related protein (LRP) is
a novel protein associated with drug resistance. The expression of LRP
messenger RNA (mRNA) was evaluated by slot blot analysis in 55 patients with ATL. Of these patients, 36 had acute, 12 chronic,
and 7 lymphoma-type ATL. The expression levels of LRP
mRNA were significantly higher in chronic ATL than in lymphoma-type ATL
(P = .007). The expression of LRP mRNA was higher in
patients with white blood cell counts above 30 000/µL
(P = .038) or with abnormal lymphocyte counts above
10 000/µL (P = .007) than in the remaining patients.
The enhanced efflux of [14C]doxorubicin from nuclei
isolated from ATL cells that expressed high levels of LRP was inhibited
by a polyclonal antibody against LRP, and the accumulation of
doxorubicin in the isolated nuclei was increased by the anti-LRP
antibody. In acute and lymphoma-type ATL patients, high expression of
LRP mRNA at diagnosis correlated with shorter survival, and a Cox
proportional hazards model showed that LRP expression is an independent
prognostic factor. These findings suggest that functionally active LRP
is expressed in some ATL cells and that it is involved in drug
resistance and poor prognosis in ATL.
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