Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia

Alan F. List, Catherine S Perry, Thomas M. Grogan, Cynthia Johnson, Denise Roe, John P. Greer, Steven N. Wolff, Henricus J. Broxterman, George L. Scheffer, Rik J. Scheper, William S. Dalton

Research output: Contribution to journalArticle

230 Citations (Scopus)

Abstract

The monoclonal antibody LRP56 recognizes a 110-kD major vault protein (lung-resistance protein [LRP]) overexpressed in several P-glycoprotein- negative (Pgp-), multidrug resistant tumor cell lines. To determine the frequency of LRP overexpression, its prognostic significance, and its relation to Pgp, we analyzed bone marrow specimens from 87 consecutive patients with acute leukemia. Diagnoses included de novo acute myeloid leukemia (AML; 21 patients), leukemia arising from an antecedent hematologic disorder or prior cytotoxic therapy (secondary AML; 27 patients), AML in relapse (29 patients), and blast phase of chronic myeloid leukemia (CML-BP; 10 patients). A granular cytoplasmic staining pattern was detected by immunocytochemistry in 32 (37%) cases, including 7 (33%) de novo AML, 13 (48%) secondary AML, 11 (38%) relapsed AML, and 1 of 10 CML-BP. Among 66 evaluable patients with AML, LRP overexpression was associated with an inferior response to induction chemotherapy (P = .0017). Remissions were achieved in 35% of LRP+ patients as compared with 68% of LRP- patients. Although Pgp adversely affected response in univariate analysis (P = .0414), only LRP had independent prognostic significance when compared in a logistic regression model (P = .0046). Differences in remission duration (P = .075) and overall survival (P = .058) approached significance only for LRP. Sequential specimens from remitting patients receiving treatment with the Pgp modulator cyclosporin-A showed emergence of the LRP phenotype despite a decrease or loss of Pgp at the time of treatment failure (P = .0304). Significant associations were observed between LRP and age greater than 55 years (P = .017), Pgp (P = .040), and prior treatment with mitoxantrone (P = .020) but not with CD34. These findings indicate that overexpression of the novel transporter protein LRP is an important predictor of treatment outcome in AML.

Original languageEnglish (US)
Pages (from-to)2464-2469
Number of pages6
JournalBlood
Volume87
Issue number6
StatePublished - Mar 15 1996
Externally publishedYes

Fingerprint

Acute Myeloid Leukemia
Proteins
Emitter coupled logic circuits
Leukemia
major vault protein
Logistic Models
Blast Crisis
Mitoxantrone
Induction Chemotherapy
Chemotherapy
P-Glycoprotein
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Tumor Cell Line
Treatment Failure
Modulators
Cyclosporine
Logistics
Tumors
Bone
Therapeutics

ASJC Scopus subject areas

  • Hematology

Cite this

Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia. / List, Alan F.; Perry, Catherine S; Grogan, Thomas M.; Johnson, Cynthia; Roe, Denise; Greer, John P.; Wolff, Steven N.; Broxterman, Henricus J.; Scheffer, George L.; Scheper, Rik J.; Dalton, William S.

In: Blood, Vol. 87, No. 6, 15.03.1996, p. 2464-2469.

Research output: Contribution to journalArticle

List, AF, Perry, CS, Grogan, TM, Johnson, C, Roe, D, Greer, JP, Wolff, SN, Broxterman, HJ, Scheffer, GL, Scheper, RJ & Dalton, WS 1996, 'Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia', Blood, vol. 87, no. 6, pp. 2464-2469.
List, Alan F. ; Perry, Catherine S ; Grogan, Thomas M. ; Johnson, Cynthia ; Roe, Denise ; Greer, John P. ; Wolff, Steven N. ; Broxterman, Henricus J. ; Scheffer, George L. ; Scheper, Rik J. ; Dalton, William S. / Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia. In: Blood. 1996 ; Vol. 87, No. 6. pp. 2464-2469.
@article{f512c765f5254e67ad7a9eaa0c4c5c44,
title = "Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia",
abstract = "The monoclonal antibody LRP56 recognizes a 110-kD major vault protein (lung-resistance protein [LRP]) overexpressed in several P-glycoprotein- negative (Pgp-), multidrug resistant tumor cell lines. To determine the frequency of LRP overexpression, its prognostic significance, and its relation to Pgp, we analyzed bone marrow specimens from 87 consecutive patients with acute leukemia. Diagnoses included de novo acute myeloid leukemia (AML; 21 patients), leukemia arising from an antecedent hematologic disorder or prior cytotoxic therapy (secondary AML; 27 patients), AML in relapse (29 patients), and blast phase of chronic myeloid leukemia (CML-BP; 10 patients). A granular cytoplasmic staining pattern was detected by immunocytochemistry in 32 (37{\%}) cases, including 7 (33{\%}) de novo AML, 13 (48{\%}) secondary AML, 11 (38{\%}) relapsed AML, and 1 of 10 CML-BP. Among 66 evaluable patients with AML, LRP overexpression was associated with an inferior response to induction chemotherapy (P = .0017). Remissions were achieved in 35{\%} of LRP+ patients as compared with 68{\%} of LRP- patients. Although Pgp adversely affected response in univariate analysis (P = .0414), only LRP had independent prognostic significance when compared in a logistic regression model (P = .0046). Differences in remission duration (P = .075) and overall survival (P = .058) approached significance only for LRP. Sequential specimens from remitting patients receiving treatment with the Pgp modulator cyclosporin-A showed emergence of the LRP phenotype despite a decrease or loss of Pgp at the time of treatment failure (P = .0304). Significant associations were observed between LRP and age greater than 55 years (P = .017), Pgp (P = .040), and prior treatment with mitoxantrone (P = .020) but not with CD34. These findings indicate that overexpression of the novel transporter protein LRP is an important predictor of treatment outcome in AML.",
author = "List, {Alan F.} and Perry, {Catherine S} and Grogan, {Thomas M.} and Cynthia Johnson and Denise Roe and Greer, {John P.} and Wolff, {Steven N.} and Broxterman, {Henricus J.} and Scheffer, {George L.} and Scheper, {Rik J.} and Dalton, {William S.}",
year = "1996",
month = "3",
day = "15",
language = "English (US)",
volume = "87",
pages = "2464--2469",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "6",

}

TY - JOUR

T1 - Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia

AU - List, Alan F.

AU - Perry, Catherine S

AU - Grogan, Thomas M.

AU - Johnson, Cynthia

AU - Roe, Denise

AU - Greer, John P.

AU - Wolff, Steven N.

AU - Broxterman, Henricus J.

AU - Scheffer, George L.

AU - Scheper, Rik J.

AU - Dalton, William S.

PY - 1996/3/15

Y1 - 1996/3/15

N2 - The monoclonal antibody LRP56 recognizes a 110-kD major vault protein (lung-resistance protein [LRP]) overexpressed in several P-glycoprotein- negative (Pgp-), multidrug resistant tumor cell lines. To determine the frequency of LRP overexpression, its prognostic significance, and its relation to Pgp, we analyzed bone marrow specimens from 87 consecutive patients with acute leukemia. Diagnoses included de novo acute myeloid leukemia (AML; 21 patients), leukemia arising from an antecedent hematologic disorder or prior cytotoxic therapy (secondary AML; 27 patients), AML in relapse (29 patients), and blast phase of chronic myeloid leukemia (CML-BP; 10 patients). A granular cytoplasmic staining pattern was detected by immunocytochemistry in 32 (37%) cases, including 7 (33%) de novo AML, 13 (48%) secondary AML, 11 (38%) relapsed AML, and 1 of 10 CML-BP. Among 66 evaluable patients with AML, LRP overexpression was associated with an inferior response to induction chemotherapy (P = .0017). Remissions were achieved in 35% of LRP+ patients as compared with 68% of LRP- patients. Although Pgp adversely affected response in univariate analysis (P = .0414), only LRP had independent prognostic significance when compared in a logistic regression model (P = .0046). Differences in remission duration (P = .075) and overall survival (P = .058) approached significance only for LRP. Sequential specimens from remitting patients receiving treatment with the Pgp modulator cyclosporin-A showed emergence of the LRP phenotype despite a decrease or loss of Pgp at the time of treatment failure (P = .0304). Significant associations were observed between LRP and age greater than 55 years (P = .017), Pgp (P = .040), and prior treatment with mitoxantrone (P = .020) but not with CD34. These findings indicate that overexpression of the novel transporter protein LRP is an important predictor of treatment outcome in AML.

AB - The monoclonal antibody LRP56 recognizes a 110-kD major vault protein (lung-resistance protein [LRP]) overexpressed in several P-glycoprotein- negative (Pgp-), multidrug resistant tumor cell lines. To determine the frequency of LRP overexpression, its prognostic significance, and its relation to Pgp, we analyzed bone marrow specimens from 87 consecutive patients with acute leukemia. Diagnoses included de novo acute myeloid leukemia (AML; 21 patients), leukemia arising from an antecedent hematologic disorder or prior cytotoxic therapy (secondary AML; 27 patients), AML in relapse (29 patients), and blast phase of chronic myeloid leukemia (CML-BP; 10 patients). A granular cytoplasmic staining pattern was detected by immunocytochemistry in 32 (37%) cases, including 7 (33%) de novo AML, 13 (48%) secondary AML, 11 (38%) relapsed AML, and 1 of 10 CML-BP. Among 66 evaluable patients with AML, LRP overexpression was associated with an inferior response to induction chemotherapy (P = .0017). Remissions were achieved in 35% of LRP+ patients as compared with 68% of LRP- patients. Although Pgp adversely affected response in univariate analysis (P = .0414), only LRP had independent prognostic significance when compared in a logistic regression model (P = .0046). Differences in remission duration (P = .075) and overall survival (P = .058) approached significance only for LRP. Sequential specimens from remitting patients receiving treatment with the Pgp modulator cyclosporin-A showed emergence of the LRP phenotype despite a decrease or loss of Pgp at the time of treatment failure (P = .0304). Significant associations were observed between LRP and age greater than 55 years (P = .017), Pgp (P = .040), and prior treatment with mitoxantrone (P = .020) but not with CD34. These findings indicate that overexpression of the novel transporter protein LRP is an important predictor of treatment outcome in AML.

UR - http://www.scopus.com/inward/record.url?scp=13344278004&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13344278004&partnerID=8YFLogxK

M3 - Article

C2 - 8630412

AN - SCOPUS:13344278004

VL - 87

SP - 2464

EP - 2469

JO - Blood

JF - Blood

SN - 0006-4971

IS - 6

ER -