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Expression of the Lung Resistance Protein Predicts Poor Outcome in De
Novo Acute Myeloid Leukemia
Martin Filipits,
Gudrun Pohl,
Thomas Stranzl,
Ralf W. Suchomel,
Rik J. Scheper,
Ulrich Jäger,
Klaus Geissler,
Klaus Lechner, and
Robert Pirker
From the Divisions of Oncology and Hematology, the Department of
Internal Medicine I, University of Vienna Medical School, Vienna,
Austria; and the Department of Pathology, Free University Hospital,
Amsterdam, The Netherlands.
The 110-kD lung resistance protein (LRP) is
overexpressed in P-glycoprotein-negative multidrug-resistant cell
lines and most likely involved in the multidrug resistance (MDR) of
these cell lines. To determine the clinical significance of LRP, we
have studied LRP expression of leukemic blasts and its association with
clinical outcome in patients with de novo acute myeloid leukemia (AML).
LRP expression of leukemic blasts obtained from peripheral blood or
bone marrow of previously untreated patients (n = 86) was
determined by immunocytochemistry by means of monoclonal antibody LRP-56. LRP expression at diagnosis was detected in 31 (36%) patients. LRP expression was independent of age and sex of the patients, French-American-British subtype, cytogenetic abnormalities, and lactate
dehydrogenase levels, but correlated with white blood cell count
(P = .01). Eighty-two patients received standard induction chemotherapy that included cytarabine and MDR drugs (daunorubicin in
most patients, additional etoposide in the majority of patients). The
complete remission rate of induction chemotherapy was 72% (95%
confidence interval [CI] = 61% to 82%) for the total study population. The complete remission rate was 81% (95% CI = 67% to
91%) for patients without LRP expression but only 55% (95% CI = 36% to 74%) for patients with LRP expression
(P = .01). Overall survival and disease-free survival were
estimated according to Kaplan-Meier in 82 and 59 patients,
respectively. Overall survival was significantly longer in patients
without LRP expression than in patients with LRP expression. At a
median follow-up of 16 months, median overall survival was 17 months
(95% CI = 12 to 38 months) for LRP-negative patients but only 8 months (95% CI = 4 to 12 months) for -positive patients
(P = .006). Disease-free survival was 9 months (95%
CI = 7 to 11 months) for LRP-negative patients and 6 months (95%
CI = 5 to 8 months) for -positive patients (P = .078). Outcome was best in patients lacking both LRP and P-glycoprotein expression. In conclusion, LRP predicts for poor outcome and thus the
LRP gene appears to be another clinically relevant drug
resistance gene in AML.
Blood, Vol. 91 No. 5 (March 1), 1998:
pp. 1508-1513
© 1998 by The American Society of Hematology.
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