PEGYLATED MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR ABROGATES THE LETHAL THROMBOCYTOPENIA ASSOCIATED WITH CARBOPLATIN AND IRRADIATION IN MICE

被引：157

作者：

HOKOM, MM ^{[1
]}

LACEY, D ^{[1
]}

KINSTLER, OB ^{[1
]}

CHOI, E ^{[1
]}

KAUFMAN, S ^{[1
]}

FAUST, J ^{[1
]}

ROWAN, C ^{[1
]}

DWYER, E ^{[1
]}

NICHOL, JL ^{[1
]}

GRASEL, T ^{[1
]}

WILSON, J ^{[1
]}

STEINBRINK, R ^{[1
]}

HECHT, R ^{[1
]}

WINTERS, D ^{[1
]}

BOONE, T ^{[1
]}

HUNT, P ^{[1
]}

机构：

[1] AMGEN INC,AMGEN CTR,THOUSAND OAKS,CA 91320

来源：

BLOOD | 1995年 / 86卷 / 12期

关键词：

D O I：

10.1182/blood.V86.12.4486.bloodjournal86124486

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Megakaryocyte growth and development factor (MGDF) is a potent inducer of megakaryopoiesis in vitro and thrombopoiesis in vivo. The effects of MGDF appear to be lineage-selective, making this cytokine an ideal candidate for use in alleviating clinically relevant thrombocytopenias. This report describes a murine model of life-threatening thrombocytopenia that results from the combination treatment of carboplatin and sublethal irradiation. Mortality of this regimen is 94% and is associated with widespread internal bleeding. The daily administration of pegylated recombinant human MGDF (PEG-rMGDF) significantly reduced mortality (to <15%) and ameliorated the depth and duration of thrombocytopenia. The severity of leucopenia and anemia was also reduced, although it was not clear whether these effects were direct. Platelets generated in response to PEG-rMGDF were morphologically indistinguishable from normal platelets. PEG-rMGDF administered in combination with murine granulocyte colony-stimulating factor completely prevented mortality and further reduced leukopenia and thrombocytopenia. These data support the concept that PEG-rMGDF may be useful to treat iatrogenic thrombocytopenias. (C) 1995 by The American Society of Hematology.

引用

页码：4486 / 4492

页数：7

共 31 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] THROMBOPOIETIN (C-MPL LIGAND) ACTS SYNERGISTICALLY WITH ERYTHROPOIETIN, STEM-CELL FACTOR, AND INTERLEUKIN-11 TO ENHANCE MURINE MEGAKARYOCYTE COLONY GROWTH AND INCREASES MEGAKARYOCYTE PLOIDY IN-VITRO [J].

BROUDY, VC ;

LIN, NL ;

KAUSHANSKY, K .

BLOOD, 1995, 85 (07) :1719-1726

[3]

CAIRO MS, 1994, EXP HEMATOL, V22, P1118

[4]

CARRINGTON PA, 1992, EXP HEMATOL, V20, P462

[5] RECOMBINANT HUMAN MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR (RHUMGDF), A LIGAND FOR C-MPL, PRODUCES FUNCTIONAL HUMAN PLATELETS IN-VITRO [J].

CHOI, ES ;

HOKOM, M ;

BARTLEY, T ;

LI, YS ;

OHASHI, H ;

KATO, T ;

NICHOL, JL ;

SKRINE, J ;

KNUDTEN, A ;

CHEN, J ;

HORNKOHL, A ;

GRAMPP, G ;

SLEEMAN, L ;

COLE, S ;

TRAIL, G ;

HUNT, P .

STEM CELLS, 1995, 13 (03) :317-322

[6]

DELGADO C, 1992, CRIT REV THER DRUG, V9, P249

[7] 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

[8]

EDMONSON JH, 1992, CANCER, V70, P2529, DOI 10.1002/1097-0142(19921115)70:10<2529::AID-CNCR2820701023>3.0.CO

[9]

2-H

[10] RECOMBINANT HUMAN MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR STIMULATES THROMBOCYTOPOIESIS IN NORMAL NONHUMAN-PRIMATES [J].

FARESE, AM ;

HUNT, P ;

BOONE, T ;

MACVITTIE, TJ .

BLOOD, 1995, 86 (01) :54-59

← 1 2 3 4 →