p-ERK1/2 is a predictive factor of response to erythropoiesis-stimulating agents in low/int-1 myelodysplastic syndromes.
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.
Frisan
Emilie
E
Département d’Immunologie-Hématologie, Institut Cochin, INSERM U1016, 3Centre National de la Recherche Scientifique, Paris Cedex 14, France.
Pawlikowska
Patrycja
P
Pierre-Eugène
Cecile
C
Viallon
Vivian
V
Gibault
Laure
L
Park
Sophie
S
Mayeux
Patrick
P
Dreyfus
François
F
Porteu
Françoise
F
Fontenay
Michaëla
M
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004900:Erythroblasts / Q000201:enzymology* / Q000473:pathology; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000097:blood / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis*; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis*; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
D015415:Biomarkers; D006397:Hematinics; D004921:Erythropoietin; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
J Clin Oncol. 2008 Jul 20;26(21):3607-13
18559873
Blood. 2004 Jul 15;104(2):321-7
15054036
Blood. 2008 Jan 15;111(2):574-82
17940203
Br J Haematol. 1995 Jan;89(1):67-71
7833279
J Exp Med. 2002 Nov 18;196(10):1347-53
12438425
Br J Haematol. 2000 May;109(2):367-75
10848827
Hematol J. 2001;2(2):70-80
11423998
Blood. 2007 Jun 15;109(12):5473-6
17351113
Blood. 1998 Jul 1;92(1):68-75
9639501
Blood. 2007 Aug 1;110(3):1025-8
17426258
Blood. 2010 Mar 4;115(9):1779-84
20038788
Haematologica. 2006 Jun;91(6):757-64
16769577
Blood. 1996 May 15;87(10):4076-81
8639764
Br J Haematol. 2003 Mar;120(6):1037-46
12648074
Leukemia. 2005 Sep;19(9):1543-9
16001087
Blood. 2002 Mar 1;99(5):1594-601
11861273
Oncogene. 2003 Dec 18;22(58):9205-16
14681680
Radiology. 1983 Sep;148(3):839-43
6878708
Haematologica. 1999 Dec;84(12):1058-64
10586205
Br J Haematol. 1997 Nov;99(2):344-51
9375752
Clin Cancer Res. 1997 May;3(5):733-9
9815743
Blood. 2006 Jul 15;108(2):419-25
16609072