Elevated soluble MUC1 levels and decreased anti-MUC1 antibody levels in patients with multiple myeloma

被引:68
作者
Treon, SP
Maimonis, P
Bua, D
Young, G
Raje, N
Mollick, J
Chauhan, D
Tai, YT
Hideshima, T
Shima, Y
Hilgers, J
von Mensdorff-Pouilly, S
Belch, AR
Pilarski, LM
Anderson, KC
机构
[1] Dana Farber Canc Inst, Div Hematol Malignancies, Dept Adult Oncol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
[3] Bayer Diagnost, Walpole, MA USA
[4] Vrije Univ Amsterdam, Acad Hosp, Amsterdam, Netherlands
[5] Cross Canc Inst, Dept Med Oncol, Edmonton, AB T6G 1Z2, Canada
关键词
D O I
10.1182/blood.V96.9.3147.h8003147_3147_3153
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Soluble MUC1 (sMUC1) levels are elevated in many MUC1(+) cancers. We and others have shown that MUC1 is expressed on multiple myeloma (MM) plasma cells and B cells. In this study, we measured sMUC1 levels in bone marrow (BM) plasma from 71 MM patients and 21 healthy donors (HDs), and in peripheral blood (PB) plasma from 42 MM patients and 13 HDs using an immunoassay that detects the CA27.29 epitope of MUC1. sMUC1 levels were found to be significantly greater (mean 31.76 U/mL, range 5.69 to 142.48 U/mL) in MM patient BM plasma versus HD BM plasma (mean 9.68 U/mL, range 0.65 to 39.83 U/mL) (P < .001). Importantly, BM plasma sMUC1 levels were related to tumor burden because sMUC1 levels were significantly higher for NIM patients with active disease (34.62 U/mL, range 5.69 to 142.48 U/mL) versus MM patients with minimal residual disease (16.16 U/mL, range 5.7 to 56.68 U/mL) (P = .0026), sMUC1 levels were also elevated in the PB plasma of MM patients (32.79 U/mL, range 4.15 to 148.84 U/ml) versus HDs (18.47 U/ml, range 8.84 to 42.49) (P = .0052). Lastly, circulating immunglobulin M (IgM) and IgG antibodies to MUC1 were measured in 114 MM patients and 31 HDs, because natural antibodies to MUC1 have been detected in patients with other MUC1-bearing malignancies. These studies demonstrated lower levels of circulating IgM (P < .001) and IgG (P = .078) antibodies to MUC1 in MM patients compared with HDs. Our data therefore show that in MM patients, sMUC1 levels are elevated and correlate with disease burden, whereas anti-MUC1 antibody levels are decreased. (C) 2000 by The American Society of Hematology.
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页码:3147 / 3153
页数:7
相关论文
共 52 条
[1]   Cancer-associated MUC1 mucin inhibits human T-cell proliferation, which is reversible by IL-2 [J].
Agrawal, B ;
Krantz, MJ ;
Reddish, MA ;
Longenecker, BM .
NATURE MEDICINE, 1998, 4 (01) :43-49
[2]  
ALSAATI T, 1989, HUM PATHOL, V17, P533
[3]   SPECIFIC, MAJOR HISTOCOMPATIBILITY COMPLEX - UNRESTRICTED RECOGNITION OF TUMOR-ASSOCIATED MUCINS BY HUMAN CYTO-TOXIC T-CELLS [J].
BARND, DL ;
LAN, MS ;
METZGAR, RS ;
FINN, OJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (18) :7159-7163
[4]  
Baruch A, 1999, CANCER RES, V59, P1552
[5]  
BERGSAGEL PL, 1994, BLOOD, V84, pA524
[6]   IN MULTIPLE-MYELOMA, CLONOTYPIC B-LYMPHOCYTES ARE DETECTABLE AMONG CD19(+) PERIPHERAL-BLOOD CELLS EXPRESSING CD38, CD56, AND MONOTYPIC IG LIGHT-CHAIN [J].
BERGSAGEL, PL ;
SMITH, AM ;
SZCZEPEK, A ;
MANT, MJ ;
BELCH, AR ;
PILARSKI, LM .
BLOOD, 1995, 85 (02) :436-447
[7]   THE BONE-MARROW OF MULTIPLE-MYELOMA PATIENTS CONTAINS B-CELL POPULATIONS AT DIFFERENT STAGES OF DIFFERENTIATION THAT ARE CLONALLY RELATED TO THE MALIGNANT PLASMA-CELL [J].
BILLADEAU, D ;
AHMANN, G ;
GREIPP, P ;
VANNESS, B .
JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 178 (03) :1023-1031
[8]  
Bon GG, 1997, CLIN CHEM, V43, P585
[9]   THE PRODUCT OF THE HUMAN MUC1 GENE WHEN SECRETED BY MOUSE CELLS TRANSFECTED WITH THE FULL-LENGTH CDNA LACKS THE CYTOPLASMIC TAIL [J].
BOSHELL, M ;
LALANI, EN ;
PEMBERTON, L ;
BURCHELL, J ;
GENDLER, S ;
TAYLORPAPADIMITRIOU, J .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1992, 185 (01) :1-8
[10]  
BURCHELL J, 1987, CANCER RES, V47, P5476