This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tamm, I. Articles by Wuchter, C. Search for Related Content PubMed PubMed Citation Articles by Tamm, I. Articles by Wuchter, C.

High Expression Levels of X-Linked Inhibitor of Apoptosis Protein and Survivin Correlate with Poor Overall Survival in Childhood de Novo Acute Myeloid Leukemia

¹ HELIOS Klinikum Berlin, Robert-Rössle-Klinik, Department of Hematology, Oncology, and Tumor Immunology, Charité, Campus Berlin-Buch, Universitätsmedizin Berlin, Berlin; ² Department of Pediatric Hematology/Oncology, University Children’s Hospital Münster, Munster; ³ Oncogenetic Laboratory, Children’s Hospital, Justus-Liebig-University of Giessen, Giessen; and ⁴ Department of Hematology and Oncology, Charité, Campus Virchow, Humboldt-University of Berlin, Berlin, Germany

Purpose: Apoptosis-related proteins are important molecules for predicting chemotherapy response and prognosis in adult acute myeloid leukemia (AML). However, data on the expression and prognostic impact of these molecules in childhood AML are rare.

Experimental Design: Using flow cytometry and Western blot analysis, we, therefore, investigated 45 leukemic cell samples from children with de novo AML enrolled and treated within the German AML-BFM93 study for the expression of apoptosis-regulating proteins [CD95, Bcl-2, Bax, Bcl-xL, procaspase-3, X-linked inhibitor of apoptosis protein (XIAP), cellular inhibitor of apoptosis protein–1 (cIAP-1), survivin].

Results: XIAP (P < 0.002) but no other apoptosis regulators showed maturation-dependent expression differences as determined by French-American-British (FAB) morphology with the highest expression levels observed within the immature M0/1 subtypes. XIAP (P < 0.01) and Bcl-xL (P < 0.01) expression was lower in patients with favorable rather than intermediate/poor cytogenetics. After a mean follow-up of 34 months, a shorter overall survival was associated with high expression levels of XIAP [30 (n = 10) versus 41 months (n = 34); P < 0.05] and survivin [27 (n = 10) versus 41 months (n = 34); P < 0.05].

Conclusions: We conclude that apoptosis-related molecules are associated with maturation stage, cytogenetic risk groups, and therapy outcome in childhood de novo AML. The observed association of XIAP with immature FAB types, intermediate/poor cytogenetics, and poor overall survival should be confirmed within prospective pediatric AML trials.

This article has been cited by other articles:

				Q. Jin, L. Feng, C. Behrens, B. N. Bekele, I. I. Wistuba, W.-K. Hong, and H.-Y. Lee Implication of AMP-Activated Protein Kinase and Akt-Regulated Survivin in Lung Cancer Chemopreventive Activities of Deguelin Cancer Res., December 15, 2007; 67(24): 11630 - 11639. [Abstract] [Full Text] [PDF]

				D. B. Seligson, F. Hongo, S. Huerta-Yepez, Y. Mizutani, T. Miki, H. Yu, S. Horvath, D. Chia, L. Goodglick, and B. Bonavida Expression of X-Linked Inhibitor of Apoptosis Protein Is a Strong Predictor of Human Prostate Cancer Recurrence Clin. Cancer Res., October 15, 2007; 13(20): 6056 - 6063. [Abstract] [Full Text] [PDF]

				A. Troeger, M. Siepermann, G. Escherich, R. Meisel, R. Willers, S. Gudowius, T. Moritz, H.-J. Laws, H. Hanenberg, U. Goebel, et al. Survivin and its prognostic significance in pediatric acute B-cell precursor lymphoblastic leukemia Haematologica, August 1, 2007; 92(8): 1043 - 1050. [Abstract] [Full Text] [PDF]

				U. Testa and R. Riccioni Deregulation of apoptosis in acute myeloid leukemia Haematologica, January 1, 2007; 92(1): 81 - 94. [Abstract] [Full Text] [PDF]

				E. C. LaCasse, G. G. Cherton-Horvat, K. E. Hewitt, L. J. Jerome, S. J. Morris, E. R. Kandimalla, D. Yu, H. Wang, W. Wang, R. Zhang, et al. Preclinical Characterization of AEG35156/GEM 640, a Second-Generation Antisense Oligonucleotide Targeting X-Linked Inhibitor of Apoptosis Clin. Cancer Res., September 1, 2006; 12(17): 5231 - 5241. [Abstract] [Full Text] [PDF]

				B. Gyurkocza, J. Plescia, C. M. Raskett, D. S. Garlick, P. A. Lowry, B. Z. Carter, M. Andreeff, M. Meli, G. Colombo, and D. C. Altieri Antileukemic activity of shepherdin and molecular diversity of hsp90 inhibitors. J Natl Cancer Inst, August 2, 2006; 98(15): 1068 - 1077. [Abstract] [Full Text] [PDF]

				S. Fukuda and L. M. Pelus Survivin, a cancer target with an emerging role in normal adult tissues Mol. Cancer Ther., May 1, 2006; 5(5): 1087 - 1098. [Abstract] [Full Text] [PDF]

				U. Fischer and K. Schulze-Osthoff New Approaches and Therapeutics Targeting Apoptosis in Disease Pharmacol. Rev., June 1, 2005; 57(2): 187 - 215. [Abstract] [Full Text] [PDF]

				A. D. Schimmer and S. Dalili Targeting the IAP Family of Caspase Inhibitors as an Emerging Therapeutic Strategy Hematology, January 1, 2005; 2005(1): 215 - 219. [Abstract] [Full Text] [PDF]