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| Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia |
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| Author(s): List AF, Spier CS, Grogan TM, Johnson C, Roe DJ, Greer JP, Wolff SN, Broxterman HJ, Scheffer GL, Scheper RJ, Dalton WS |
| Source: BLOOD Volume: 87 Issue: 6 Pages: 2464-2469 Published: MAR 15 1996 |
| Times Cited: 195 References: 47 |
| 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. (C) 1996 by The American Society of Hematology. |
| Document Type: Article |
| Language: English |
| Reprint Address: List, AF (reprint author), UNIV ARIZONA, ARIZONA CANC CTR, HEMATOL ONCOL SECT, ROOM 3947, TUCSON, AZ 85724 USA |
Addresses:
1. UNIV ARIZONA, ARIZONA CANC CTR, BONE MARROW TRANSPLANT PROGRAM, TUCSON, AZ 85724 USA
2. UNIV ARIZONA, COLL MED, DEPT MED, TUCSON, AZ 85724 USA
3. UNIV ARIZONA, COLL MED, DEPT PATHOL, TUCSON, AZ 85724 USA
4. UNIV ARIZONA, COLL MED, DEPT PHARMACOL TOXICOL, TUCSON, AZ 85724 USA
5. UNIV ARIZONA, COLL MED, DEPT FAMILY & COMMUNITY MED, TUCSON, AZ 85724 USA
6. VANDERBILT UNIV, MED CTR, DIV HEMATOL, NASHVILLE, TN 37240 USA
7. VANDERBILT UNIV, MED CTR, DIV MED ONCOL, NASHVILLE, TN 37240 USA
8. FREE UNIV AMSTERDAM HOSP, DEPT PATHOL, AMSTERDAM, NETHERLANDS |
| Publisher: W B SAUNDERS CO, INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 |
| Subject Category: Hematology |
| IDS Number: UA957 |
| ISSN: 0006-4971 |
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