p-ERK1/2 is a predictive factor of response to erythropoiesis-stimulating agents in low/int-1 myelodysplastic syndromes

被引:25
作者
Frisan, Emilie [1 ,2 ,3 ,5 ]
Pawlikowska, Patrycja [1 ,2 ,3 ]
Pierre-Eugene, Cecile [1 ,2 ,3 ,4 ]
Viallon, Vivian [5 ,6 ]
Gibault, Laure [5 ,7 ]
Park, Sophie [1 ,2 ,3 ,5 ,8 ]
Mayeux, Patrick [1 ,2 ,3 ]
Dreyfus, Francois [1 ,2 ,3 ,5 ,8 ]
Porteu, Francoise [1 ,2 ,3 ]
Fontenay, Michaela [1 ,2 ,3 ,5 ]
机构
[1] Inst Cochin, Dept Immunol Hematol, Paris, France
[2] INSERM, U1016, F-75654 Paris 13, France
[3] CNRS, UMR 8104, F-75700 Paris, France
[4] Hop Broca Cochin Hotel Dieu, Assistance Publ Hop Paris, Serv Hematol Biol, Paris, France
[5] Univ Paris 05, Fac Med, Paris, France
[6] Hop Cochin, Assistance Publ Hop Paris, Dept Epidemiol & Biostat, F-75679 Paris 14, France
[7] Hop Cochin, Assistance Publ Hop Paris, Serv Anatomopathol, F-75679 Paris 14, France
[8] Hop Cochin, Assistance Publ Hop Paris, Serv Med Interne, Unite Fonct Hematol, F-75679 Paris 14, France
来源
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL | 2010年 / 95卷 / 11期
关键词
myelodysplastic syndromes; red cells; MAPkinase; erythropoiesis-stimulating agents; PHOSPHOINOSITIDE; 3-KINASE/AKT; PLUS ERYTHROPOIETIN; G-CSF; ANEMIA; PHOSPHORYLATION; DIFFERENTIATION; ACTIVATION; SURVIVAL; LEUKEMIA; PROPOSAL;
D O I
10.3324/haematol.2010.024349
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Serum erythropoietin level less than 100U/L and a transfusion requirement of less than 2 units per month are the best predictive factors for response to treatment by erythropoiesis-stimulating agents in low/int-1 myelodysplastic syndromes. To investigate the factors influencing the response to erythropoiesis-stimulating agents, we enrolled 127 low/int-1 myelodysplastic syndrome patients at diagnosis in a biological study of erythropoiesis. The 54 non-responders had a significantly lower number of burst-forming unit-erythroid and colony-forming unit-erythroid than responders. Erythropoietin-dependent proliferation and survival, and phospho (p)-ERK1/2 expression in steady state and after erythropoietin stimulation were defective in cultured erythroblasts. By flow cytometry, p-ERK1/2 was significantly lower in bone marrow CD45(-)/CD71(+)/GPA(-) cells from non-responders compared to responders or controls. Receiver Operator Characteristic curve analysis showed that this flow cytometry test was a sensitive biomarker for predicting the response to erythropoiesis-stimulating agents.
引用
收藏
页码:1964 / 1968
页数:5
相关论文
共 22 条
[1]  
Bardet V, 2006, HAEMATOLOGICA, V91, P757
[2]   Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes:: a randomized, controlled trial [J].
Casadevall, N ;
Durieux, P ;
Dubois, S ;
Hemery, F ;
Lepage, E ;
Quarré, MC ;
Damaj, G ;
Giraudier, S ;
Guerci, A ;
Laurent, G ;
Dombret, H ;
Chomienne, C ;
Ribrag, V ;
Stamatoullas, A ;
Marie, JP ;
Vekhoff, A ;
Maloisel, F ;
Navarro, R ;
Dreyfus, F ;
Fenaux, P .
BLOOD, 2004, 104 (02) :321-327
[3]   Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia [J].
Cheson, Bruce D. ;
Greenberg, Peter L. ;
Bennett, John M. ;
Lowenberg, Bob ;
Wijermans, Pierre W. ;
Nimer, Stephen D. ;
Pinto, Antonio ;
Beran, Miloslav ;
de Witte, Theo M. ;
Stone, Richard M. ;
Mittelman, Moshe ;
Sanz, Guillermo F. ;
Gore, Steven D. ;
Schiffer, Charles A. ;
Kantarjian, Hagop .
BLOOD, 2006, 108 (02) :419-425
[4]   In vitro proliferation and differentiation of erythroid progenitors from patients with myelodysplastic syndromes: evidence for Fas-dependent apoptosis [J].
Claessens, YE ;
Bouscary, D ;
Dupont, JM ;
Picard, F ;
Melle, J ;
Gisselbrecht, S ;
Lacombe, C ;
Dreyfus, F ;
Mayeux, P ;
Fontenay-Roupie, M .
BLOOD, 2002, 99 (05) :1594-1601
[5]   The MEK-1/ERKs signalling pathway is differentially involved in the self-renewal of early and late avian erythroid progenitor cells [J].
Dazy, S ;
Damiola, F ;
Parisey, N ;
Beug, H ;
Gandrillon, O .
ONCOGENE, 2003, 22 (58) :9205-9216
[6]   ERK1/2 phosphorylation is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia [J].
Gregorj, Chiara ;
Ricciardi, Maria R. ;
Petrucci, Maria T. ;
Scerpa, Maria C. ;
De Cave, Fabiana ;
Fazi, Paola ;
Vignetti, Marco ;
Vitale, Antonella ;
Mancini, Marco ;
Cimino, Giuseppe ;
Palmieri, Salvatore ;
Di Raimondo, Francesco ;
Specchia, Giorgina ;
Fabbiano, Francesco ;
Cantore, Nicola ;
Mosna, Federico ;
Camera, Andrea ;
Luppi, Mario ;
Annino, Luciana ;
Miraglia, Eustachio ;
Fioritoni, Giuseppe ;
Ronco, Francesca ;
Meloni, Giovanna ;
Mandelli, Franco ;
Andreeff, Michael ;
Milella, Michele ;
Foa, Robin ;
Tafuri, Agostino .
BLOOD, 2007, 109 (12) :5473-5476
[7]   A METHOD OF COMPARING THE AREAS UNDER RECEIVER OPERATING CHARACTERISTIC CURVES DERIVED FROM THE SAME CASES [J].
HANLEY, JA ;
MCNEIL, BJ .
RADIOLOGY, 1983, 148 (03) :839-843
[8]   Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin:: Results from a randomized phase II study and long-term follow-up of 71 patients [J].
Hellström-Lindberg, E ;
Ahlgren, T ;
Beguin, Y ;
Carlsson, M ;
Carneskog, J ;
Dahl, IM ;
Dybedal, I ;
Grimfors, G ;
Kanter-Lewensohn, L ;
Linder, O ;
Luthman, M ;
Löfvenberg, E ;
Nilsson-Ehle, H ;
Samuelsson, J ;
Tangen, JM ;
Winqvist, I ;
Öberg, G ;
Österborg, A ;
Öst, Å .
BLOOD, 1998, 92 (01) :68-75
[9]   A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin plus granulocyte colony-stimulating factor:: significant effects on quality of life [J].
Hellström-Lindberg, E ;
Gulbrandsen, N ;
Lindberg, G ;
Ahlgren, T ;
Dahl, IMS ;
Dybedal, I ;
Grimfors, G ;
Hesse-Sundin, E ;
Hjorth, M ;
Kanter-Lewensohn, L ;
Linder, O ;
Luthman, M ;
Löfvenberg, E ;
Öberg, G ;
Porwit-MacDonald, A ;
Rådlund, A ;
Samuelsson, J ;
Tangen, JM ;
Winquist, I ;
Wisloff, F .
BRITISH JOURNAL OF HAEMATOLOGY, 2003, 120 (06) :1037-1046
[10]   Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model [J].
HellstromLindberg, E ;
Negrin, R ;
Stein, R ;
Krantz, S ;
Lindberg, G ;
Vardiman, J ;
Ost, A ;
Greenberg, P .
BRITISH JOURNAL OF HAEMATOLOGY, 1997, 99 (02) :344-351