Expression of phosphorylated signal transducer and activator of transcription 5 is associated with an increased risk of death in acute myeloid leukemia

被引:16
作者
Brady, Anna [1 ]
Gibson, Sarah
Rybicki, Lisa
Hsi, Eric
Saunthararajah, Yogen [1 ]
Sekeres, Mikkael A. [1 ]
Tiu, Ramon [1 ]
Copelan, Edward [1 ]
Kalaycio, Matt [1 ]
Sobecks, Ronald [1 ]
Bates, Jennifer [1 ]
Advani, Anjali S. [1 ]
机构
[1] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44195 USA
关键词
acute myeloid leukemia; STAT5; phosphorylation; prognosis; STAT5; INDUCTION; CANCER;
D O I
10.1111/j.1600-0609.2012.01825.x
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Background Constitutive activation of STAT5 (by phosphorylation) has been identified in a number of malignancies, including acute myeloid leukemia (AML). Objectives We investigated whether the level of phosphorylated STAT5 (pSTAT5) expression correlates with clinical outcome in AML. Methods Adult patients with newly diagnosed AML receiving induction chemotherapy and with an available diagnostic bone marrow were evaluated. Results Forty-two percent of patients had pSTAT5 expression >0 on immunohistochemical analysis of fixed bone marrow core biopsies. In multivariable analyses, controlling for age, history of antecedent hematologic disorder, cytogenetic risk, and WBC at diagnosis, pSTAT5 expression was significantly associated with an increased risk of death (HR 1.96, 95% CI 1.193.23, P similar to=similar to 0.008) and of relapse after achieving complete remission (HR 2.31, 95% CI 1.164.63, P similar to=similar to 0.018). Conclusions Validation of pSTAT5's prognostic value requires additional study in a larger group of uniformly treated patients. However, our data suggests that targeting this signaling pathway in AML may improve the outcome of patients.
引用
收藏
页码:288 / 293
页数:6
相关论文
共 17 条
[1]
Bone marrow phospho-STAT5 expression in non-CML chronic myeloproliferative disorders correlates with JAK2 V617F mutation and provides evidence of in vivo JAK2 activation [J].
Aboudola, Samer ;
Murugesan, Guruanthan ;
Szpurka, Hadrian ;
Ramsingh, Giri ;
Zhao, Xiaoxian ;
Prescott, Nichole ;
Tubbs, Raymond R. ;
Maciejewski, Jaroslaw P. ;
Hsi, Eric D. .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2007, 31 (02) :233-239
[2]
The influence of antisense oligonucleotides against STAT5 on the regulation of normal haematopoiesis in a bone marrow model [J].
Baskiewicz-Masiuk, M ;
Paczkowski, M ;
Machalinski, B .
CELL PROLIFERATION, 2004, 37 (03) :231-245
[3]
Expression of Activated STAT5 in Neoplastic Mast Cells in Systemic Mastocytosis [J].
Baumgartner, Christian ;
Cerny-Reiterer, Sabine ;
Sonneck, Karoline ;
Mayerhofer, Matthias ;
Gleixner, Karoline V. ;
Fritz, Richard ;
Kerenyi, Marc ;
Boudot, Cedric ;
Gouilleux, Fabrice ;
Kornfeld, Jan-Wilhelm ;
Sillaber, Christian ;
Moriggl, Richard ;
Valent, Peter .
AMERICAN JOURNAL OF PATHOLOGY, 2009, 175 (06) :2416-2429
[4]
Signal transducer and activator of transcription 5 (STAT5) [J].
Buitenhuis, M ;
Coffer, PJ ;
Koenderman, L .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2004, 36 (11) :2120-2124
[5]
Cytoplasmic localization of phosphorylated STAT5 in human acute myeloid leukemia is inversely correlated with Flt3-ITD [J].
Bunting, Kevin D. ;
Xie, Xiu Yan ;
Warshawsky, Iika ;
Hsi, Eric D. .
BLOOD, 2007, 110 (07) :2775-2776
[6]
Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia:: results from Cancer and Leukemia Group B (CALGB 8461) [J].
Byrd, JC ;
Mrózek, K ;
Dodge, RK ;
Carroll, AJ ;
Edwards, CG ;
Arthur, DC ;
Pettenati, MJ ;
Patil, SR ;
Rao, KW ;
Watson, MS ;
Koduru, PRK ;
Moore, JO ;
Stone, RM ;
Mayer, RJ ;
Feldman, EJ ;
Davey, FR ;
Schiffer, CA ;
Larson, RA ;
Bloomfield, CD .
BLOOD, 2002, 100 (13) :4325-4336
[7]
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
[8]
JAK-STAT PATHWAYS AND TRANSCRIPTIONAL ACTIVATION IN RESPONSE TO IFNS AND OTHER EXTRACELLULAR SIGNALING PROTEINS [J].
DARNELL, JE ;
KERR, IM ;
STARK, GR .
SCIENCE, 1994, 264 (5164) :1415-1421
[9]
Anti-apoptotic role of STAT5 in haematopoietic cells and in the pathogenesis of malignancies [J].
Debierre-Grockiego, F .
APOPTOSIS, 2004, 9 (06) :717-728
[10]
Modeling the functional heterogeneity of leukemia stem cells: role of STAT5 in leukemia stem cell self-renewal [J].
Heuser, Michael ;
Sly, Laura M. ;
Argiropoulos, Bob ;
Kuchenbauer, Florian ;
Lai, Courteney ;
Weng, Andrew ;
Leung, Malina ;
Lin, Grace ;
Brookes, Christy ;
Fung, Stephen ;
Valk, Peter J. ;
Delwel, Ruud ;
Loewenberg, Bob ;
Krystal, Gerald ;
Humphries, R. Keith .
BLOOD, 2009, 114 (19) :3983-3993