Circulating thrombopoietin concentrations in thrombocytopenic patients, including cancer patients following chemotherapy, with or without peripheral blood progenitor cell transplantation

被引:62
作者
Meng, YG
Martin, TG
Peterson, ML
Shuman, MA
Cohen, RL
Wong, WL
机构
[1] GENENTECH INC,DEPT MOL ONCOL,S SAN FRANCISCO,CA 94080
[2] UNIV SAN FRANCISCO,DIV HEMATOL & ONCOL,SAN FRANCISCO,CA 94117
关键词
TPO; ELISA; platelet; thrombocytopenia; cell transplantation;
D O I
10.1046/j.1365-2141.1996.d01-1933.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Thrombopoietin, the ligand for the c-mpl receptor, promotes proliferation and maturation of megakaryocytes, an ELISA using a chimaeric receptor, mpl-IgG, for capture, and rabbit antibody to thrombopoietin for detection was developed for the quantitation of thrombopoietin in human serum or plasma, This ELISA preferentially detects full-length thrombopoietin compared to the bioactive N-terminal half of the molecule which has homology to erythropoietin, Thrombopoietin was not detected (<0.16 ng/ml) in 88/89 healthy individuals, However, elevated thrombopoietin concentrations of up to 3 ng/ml were detected in 59/63 thrombocytopenic patients, including cancer patients following chemotherapy. In cancer patients receiving chemotherapy with (n = 12) or without (n = 6) peripheral blood progenitor cell transplantation, thrombopoietin concentrations varied inversely with platelet counts throughout, the treatment period. In general, patients who received myeloablative chemotherapy on days -7 to -2 and peripheral blood progenitor cell transplantation on day 0 had high thrombopoietin levels (0.6-2.9 ng/ml) around day 5. Low platelet counts (< 20 x 10(9)/l) occurred between days 4 and 9, Patients who received high-dose chemotherapy on day 1 (equivalent to day -7 for transplantation patients) to day 6 without transplantation had high thrombopoietin concentrations (1.4-2.3 ng/ml) around day 13 and low platelet counts occurred between days 7 and 17.
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收藏
页码:535 / 541
页数:7
相关论文
共 22 条
[1]   IDENTIFICATION AND CLONING OF A MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR THAT IS A LIGAND FOR THE CYTOKINE RECEPTOR MPL [J].
BARTLEY, TD ;
BOGENBERGER, J ;
HUNT, P ;
LI, YS ;
LU, HS ;
MARTIN, F ;
CHANG, MS ;
SAMAL, B ;
NICHOL, JL ;
SWIFT, S ;
JOHNSON, MJ ;
HSU, RY ;
PARKER, VP ;
SUGGS, S ;
SKRINE, JD ;
MEREWETHER, LA ;
CLOGSTON, C ;
HSU, E ;
HOKOM, MM ;
HORNKOHL, A ;
CHOI, E ;
PANGELINAN, M ;
SUN, Y ;
MAR, V ;
MCNINCH, J ;
SIMONET, L ;
JACOBSEN, F ;
XIE, C ;
SHUTTER, J ;
CHUTE, H ;
BASU, R ;
SELANDER, L ;
TROLLINGER, D ;
SIEU, L ;
PADILLA, D ;
TRAIL, G ;
ELLIOTT, G ;
IZUMI, R ;
COVEY, T ;
CROUSE, J ;
GARCIA, A ;
XU, W ;
DELCASTILLO, J ;
BIRON, J ;
COLE, S ;
HU, MCT ;
PACIFICI, R ;
PONTING, I ;
SARIS, C ;
WEN, D .
CELL, 1994, 77 (07) :1117-1124
[2]   STIMULATION OF MEGAKARYOCYTOPOIESIS AND THROMBOPOIESIS BY THE C-MPL LIGAND [J].
DESAUVAGE, FJ ;
HASS, PE ;
SPENCER, SD ;
MALLOY, BE ;
GURNEY, AL ;
SPENCER, SA ;
DARBONNE, WC ;
HENZEL, WJ ;
WONG, SC ;
KUANG, WJ ;
OLES, KJ ;
HULTGREN, B ;
SOLBERG, LA ;
GOEDDEL, DV ;
EATON, DL .
NATURE, 1994, 369 (6481) :533-538
[3]  
DESAUVAGE FJ, 1996, J EXP MED, V183, P1
[4]   Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction [J].
Emmons, RVB ;
Reid, DM ;
Cohen, RL ;
Meng, G ;
Young, NS ;
Dunbar, CE ;
Shulman, NR .
BLOOD, 1996, 87 (10) :4068-4071
[5]   Regulation of thrombopoietin levels by c-mpl - Mediated binding to platelets [J].
Fielder, PJ ;
Gurney, AL ;
Stefanich, E ;
Marian, M ;
Moore, MW ;
CarverMoore, K ;
deSauvage, FJ .
BLOOD, 1996, 87 (06) :2154-2161
[6]  
GORDON MS, 1992, BLOOD, V80, P302
[7]   GENOMIC STRUCTURE, CHROMOSOMAL LOCALIZATION, AND CONSERVED ALTERNATIVE SPLICE FORMS OF THROMBOPOIETIN [J].
GURNEY, AL ;
KUANG, WJ ;
XIE, MH ;
MALLOY, BE ;
EATON, DL ;
DESAUVAGE, FJ .
BLOOD, 1995, 85 (04) :981-988
[8]   PURIFICATION AND BIOLOGIC CHARACTERIZATION OF PLASMA-DERIVED MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR [J].
HUNT, P ;
LI, YS ;
NICHOL, JL ;
HOKOM, MM ;
BOGENBERGER, JM ;
SWIFT, SE ;
SKRINE, JD ;
HORNKOHL, AC ;
LU, H ;
CLOGSTON, C ;
MEREWETHER, LA ;
JOHNSON, MJ ;
PARKER, V ;
KNUDTEN, A ;
FARESE, A ;
HSU, RY ;
GARCIA, A ;
STEAD, R ;
BOSSELMAN, RA ;
BARTLEY, TD .
BLOOD, 1995, 86 (02) :540-547
[9]   PURIFICATION AND CHARACTERIZATION OF THROMBOPOIETIN [J].
KATO, T ;
OGAMI, K ;
SHIMADA, Y ;
IWAMATSU, A ;
SOHMA, Y ;
AKAHORI, H ;
HORIE, K ;
KOKUBO, A ;
KUDO, Y ;
MAEDA, E ;
KOBAYASHI, K ;
OHASHI, H ;
OZAWA, T ;
INOUE, H ;
KAWAMURA, K ;
MIYAZAKI, H .
JOURNAL OF BIOCHEMISTRY, 1995, 118 (01) :229-236
[10]   THROMBOPOIETIN - THE PRIMARY REGULATOR OF PLATELET PRODUCTION [J].
KAUSHANSKY, K .
BLOOD, 1995, 86 (02) :419-431