Hypoxia-inducible factor-1α protein expression is associated with poor survival in normal karyotype adult acute myeloid leukemia

被引：63

作者：

Deeb, George ^{[2
]}

Vaughan, Mary M. ^{[2
]}

McInnis, Ian ^{[1
]}

Ford, Laurie Ann ^{[1
]}

Sait, Sheila N. J. ^{[2
]}

Starostik, Petr ^{[2
]}

Wetzler, Meir ^{[1
]}

Mashtare, Terry ^{[3
,4
]}

Wang, Eunice S. ^{[1
]}

机构：

[1] Roswell Pk Canc Inst, Dept Med, Leukemia Serv, Buffalo, NY 14263 USA

[2] Roswell Pk Canc Inst, Dept Pathol & Lab Med, Buffalo, NY 14263 USA

[3] Roswell Pk Canc Inst, Dept Biostat, Buffalo, NY 14263 USA

[4] SUNY Buffalo, Dept Biostat, Buffalo, NY 14260 USA

来源：

LEUKEMIA RESEARCH | 2011年 / 35卷 / 05期

关键词：

Acute myeloid leukemia; Hypoxia; HIF-1; alpha; VEGF; Marrow immunohistochemistry; ENDOTHELIAL GROWTH-FACTOR; HISTONE DEACETYLASE INHIBITORS; CIRCULATING ANGIOGENIC CELLS; INTERNAL TANDEM DUPLICATION; FACTOR-C EXPRESSION; BONE-MARROW; VEGF-C; TRANSCRIPTIONAL ACTIVITY; PROGNOSTIC-SIGNIFICANCE; TUMOR ANGIOGENESIS;

D O I：

10.1016/j.leukres.2010.10.020

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We examined the predictive impact of HIF-1 alpha protein expression on clinical outcome of 84 normal karyotype acute myeloid leukemia (NK-AML) patients (median age 66.5 years) at our institute. Thirty percent of NK-AML cells expressed cytoplasmic HIF-1 alpha. In univariate analysis, low HIF-1 alpha (<= 5%, n = 66) was associated with improved event-free survival (p = 0.0453, HR = 0.22). Multivariate analysis incorporating age, complete remission, FLT3-ITD mutation, and marrow blast percentage demonstrated that HIF-1 alpha was independently associated with poorer overall and event-free survival. HIF-1 alpha expression correlated with VEGF-C but not VEGF-A, marrow angiogenesis, FLT3 ITD or NPM1 mutations. These results support HIF-1 alpha as an outcome marker for NK-AML. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：579 / 584

页数：6

共 48 条

[1] Metabolism and the leukemic stem cell [J].

Abdel-Wahab, Omar ;

Levine, Ross L. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2010, 207 (04) :677-680

[2] Cellular vascular endothelial growth factor is a predictor of outcome in patients with acute myeloid leukemia [J].

Aguayo, A ;

Estey, E ;

Kantarjian, H ;

Mansouri, T ;

Gidel, C ;

Keating, M ;

Giles, F ;

Estrov, Z ;

Barlogie, B ;

Albitar, M .

BLOOD, 1999, 94 (11) :3717-3721

[3] Plasma vascular endothelial growth factor levels have prognostic significance in patients with acute myeloid leukemia but not in patients with myelodysplastic syndromes [J].

Aguayo, A ;

Kantarjian, HM ;

Estey, EH ;

Giles, FJ ;

Verstovsek, S ;

Manshouri, T ;

Gidel, C ;

O'Brien, S ;

Keating, MJ ;

Albitar, M .

CANCER, 2002, 95 (09) :1923-1930

[4] Prognostic Impact of Isocitrate Dehydrogenase Enzyme Isoforms 1 and 2 Mutations in Acute Myeloid Leukemia: A Study by the Acute Leukemia French Association Group [J].

Boissel, Nicolas ;

Nibourel, Olivier ;

Renneville, Aline ;

Gardin, Claude ;

Reman, Oumedaly ;

Contentin, Nathalie ;

Bordessoule, Dominique ;

Pautas, Cecile ;

de Revel, Thierry ;

Quesnel, Bruno ;

Huchette, Pascal ;

Philippe, Nathalie ;

Geffroy, Sandrine ;

Terre, Christine ;

Thomas, Xavier ;

Castaigne, Sylvie ;

Dombret, Herve ;

Preudhomme, Claude .

JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (23) :3717-3723

[5] Hypoxia, DNA repair and genetic instability [J].

Bristow, Robert G. ;

Hill, Richard P. .

NATURE REVIEWS CANCER, 2008, 8 (03) :180-192

[6] Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia [J].

Cheson, BD ;

Bennett, JM ;

Kopecky, KJ ;

Büchner, T ;

Willman, CL ;

Estey, EH ;

Schiffer, CA ;

Döhner, H ;

Tallman, MS ;

Lister, TA ;

LoCocco, F ;

Willemze, R ;

Biondi, A ;

Hiddemann, W ;

Larson, RA ;

Löwenberg, B ;

Sanz, MA ;

Head, DR ;

Ohno, R ;

Bloomfield, CD .

JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (24) :4642-4649

[7] Vascular endothelial growth factor-C (VEGF-C) promotes angiogenesis by induction of COX-2 in leukemic cells via the VEGF-R3/JNK/AP-1 pathway [J].

Chien, Ming-Hsien ;

Ku, Chia-Chi ;

Johansson, Gunnar ;

Chen, Min-Wei ;

Hsiao, Michael ;

Su, Jen-Liang ;

Inoue, Hiroyasu ;

Hua, Kuo-Tai ;

Wei, Lin-Hung ;

Kuo, Min-Liang .

CARCINOGENESIS, 2009, 30 (12) :2005-2013

[8] Low bone marrow oxygen tension and hypoxia-inducible factor-1α overexpression characterize patients with multiple myeloma: role on the transcriptional and proangiogenic profiles of CD138+ cells [J].

Colla, S. ;

Storti, P. ;

Donofrio, G. ;

Todoerti, K. ;

Bolzoni, M. ;

Lazzaretti, M. ;

Abeltino, M. ;

Ippolito, L. ;

Neri, A. ;

Ribatti, D. ;

Rizzoli, V. ;

Martella, E. ;

Giuliani, N. .

LEUKEMIA, 2010, 24 (11) :1967-1970

[9] New vessel formation and aberrant VEGF/VEGFR signaling in acute leukemia: Does it matter? [J].

De Bont, ESJM ;

Neefjes, VME ;

Rosati, S ;

Vellenga, E ;

Kamps, WA .

LEUKEMIA & LYMPHOMA, 2002, 43 (10) :1901-1909

[10] Endogenous vascular endothelial growth factor-C expression is associated with decreased drug responsiveness in childhood acute myeloid leukemia [J].

de Jonge, Hendrik J. M. ;

Weidenaar, Alida C. ;

ter Elst, Arja ;

Boezen, H. Marike ;

Scherpen, Frank J. G. ;

Steege, Jessica C. A. Bouma-ter ;

Kaspers, Gertjan J. L. ;

Goemans, Bianca F. ;

Creutzig, Ursula ;

Zimmermann, Martin ;

Kamps, Willem A. ;

de Bont, Eveline S. J. M. .

CLINICAL CANCER RESEARCH, 2008, 14 (03) :924-930

← 1 2 3 4 5 →