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Clinical and Translational Oncology

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01-09-2019 | Acute Myeloid Leukemia | Research Article

Distinct prognostic values of Annexin family members expression in acute myeloid leukemia

Authors: Y. Niu, X. Yang, Y. Chen, X. Jin, Y. Xie, Y. Tang, L. Li, S. Liu, Y. Guo, X. Li, L. Duan, H. Wang

Published in: Clinical and Translational Oncology | Issue 9/2019

Abstract

Background

Annexin family consist of 12 members, many of them are frequently dysregulated in human cancers. However, the diagnosis and prognosis of Annexin family expression in acute myeloid leukemia (AML) remain elusive. The aim of the present study was to assess the prognostic value of Annexin expressions in adult and pediatric AML.

Methods

GenomicScape tool was used to assess the prognostic value of the expressions of Annexin family members in a cohort of 162 adult AML patients. Quantitative reverse transcript real-time PCR (QRT-PCR) was performed to detect the ANXA2 expression level in the bone marrow-derived mononuclear cells (BMMCs) obtained from 101 pediatric AML patients and 30 controls.

Results

The results demonstrated that high mRNA expressions of ANXA2, ANXA6, and ANXA7 were significantly associated with worse prognosis, while ANXA5 was correlated with better prognosis in adult AML. QRT-PCR analysis showed that ANXA2 expression was dramatically downregulated in BMMCs of pediatric AML patients compared to controls (p < 0.0001). ROC analysis demonstrated that ANXA2 could efficiently differentiate pediatric AML patients from controls (AUC 0.872, p < 0.0001). Likewise, ANXA2 was significantly lower in AML patients with poor-risk karyotype (p = 0.048). Also, the level of ANXA2 trended to decrease in AML patients who had not achieving complete remission. Moreover, patients with lower expression of ANXA2 had higher death rate (p = 0.042) and shorter overall survival (HR 0.55, p = 0.042). Thus, these findings suggest that ANXA2 exerts poor prognostic effect on adult AML but favorable prognostic effect on pediatric AML.

Conclusions

Collectively, Annexin family members exert distinct prognostic roles in AML, and ANXA2 can be used as a biological marker for diagnosis and prognosis of pediatric AML.

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Dombret H, Gardin C. An update of current treatments for adult acute myeloid leukemia. Blood. 2016;127(1):53–61. https://doi.org/10.1182/blood-2015-08-604520.CrossRefPubMedPubMedCentral

Grimwade D, Ivey A, Huntly BJ. Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance. Blood. 2016;127(1):29–41. https://doi.org/10.1182/blood-2015-07-604496.CrossRefPubMedPubMedCentral

Gerke V, Creutz CE, Moss SE. Annexins: linking Ca²⁺ signalling to membrane dynamics. Nat Rev Mol Cell Biol. 2005;6(6):449–61. https://doi.org/10.1038/nrm1661.CrossRefPubMed

Grewal T, Enrich C. Annexins–modulators of EGF receptor signalling and trafficking. Cell Signal. 2009;21(6):847–58.CrossRefPubMed

Gerke V, Moss SE. Annexins: from structure to function. Physiol Rev. 2002;82(2):331–71. https://doi.org/10.1152/physrev.00030.2001.CrossRefPubMed

Tu Y, Johnstone CN, Stewart AG. Annexin A1 influences in breast cancer: controversies on contributions to tumour, host and immunoediting processes. Pharmacol Res. 2017;119:278–88. https://doi.org/10.1016/j.phrs.2017.02.011.CrossRefPubMed

Biaoxue R, Xiguang C, Hua L, Tian F, Wenlong G. Increased level of annexin A1 in bronchoalveolar lavage fluid as a potential diagnostic indicator for lung cancer. Int J Biol Mark. 2017;32(1):e132–40. https://doi.org/10.5301/jbm.5000243.CrossRef

Rentero C, Blanco-Munoz P, Meneses-Salas E, Grewal T, Enrich C. Annexins-coordinators of cholesterol homeostasis in endocytic pathways. Int J Mol Sci. 2018. https://doi.org/10.3390/ijms19051444.CrossRefPubMedPubMedCentral

Biaoxue R, Xiguang C, Shuanying Y. Annexin A1 in malignant tumors: current opinions and controversies. Int J Biol Mark. 2014;29(1):e8–20. https://doi.org/10.5301/jbm.5000046.CrossRef

10.

Yan X, Yin J, Yao H, Mao N, Yang Y, Pan L. Increased expression of annexin A3 is a mechanism of platinum resistance in ovarian cancer. Can Res. 2010;70(4):1616–24. https://doi.org/10.1158/0008-5472.CAN-09-3215.CrossRef

11.

Lin LL, Huang HC, Juan HF. Revealing the molecular mechanism of gastric cancer marker annexin A4 in cancer cell proliferation using exon arrays. PLoS One. 2012;7(9):e44615. https://doi.org/10.1371/journal.pone.0044615.CrossRefPubMedPubMedCentral

12.

Zheng MD, Wang ND, Li XL, Yan J, Tang JH, Zhao XH, et al. Toosendanin mediates cisplatin sensitization through targeting Annexin A4/ATP7A in non-small cell lung cancer cells. J Nat Med. 2018. https://doi.org/10.1007/s11418-018-1211-0.CrossRefPubMed

13.

Haiman CA, Han Y, Feng Y, Xia L, Hsu C, Sheng X, et al. Genome-wide testing of putative functional exonic variants in relationship with breast and prostate cancer risk in a multiethnic population. PLoS Genet. 2013;9(3):e1003419. https://doi.org/10.1371/journal.pgen.1003419.CrossRefPubMedPubMedCentral

14.

Wei B, Guo C, Liu S, Sun MZ. Annexin A4 and cancer. Clinica Chimica Acta Int J Clin Chem. 2015;447:72–8. https://doi.org/10.1016/j.cca.2015.05.016.CrossRef

15.

D’Souza S, Kurihara N, Shiozawa Y, Joseph J, Taichman R, Galson DL, et al. Annexin II interactions with the annexin II receptor enhance multiple myeloma cell adhesion and growth in the bone marrow microenvironment. Blood. 2012;119(8):1888–96. https://doi.org/10.1182/blood-2011-11-393348.CrossRefPubMedPubMedCentral

16.

O’Connell PA, Madureira PA, Berman JN, Liwski RS, Waisman DM. Regulation of S100A10 by the PML-RAR-alpha oncoprotein. Blood. 2011;117(15):4095–105. https://doi.org/10.1182/blood-2010-07-298851.CrossRefPubMed

17.

Spijkers-Hagelstein JA, Mimoso Pinhancos S, Schneider P, Pieters R, Stam RW. Src kinase-induced phosphorylation of annexin A2 mediates glucocorticoid resistance in MLL-rearranged infant acute lymphoblastic leukemia. Leukemia. 2013;27(5):1063–71. https://doi.org/10.1038/leu.2012.372.CrossRefPubMed

18.

Chiang Y, Davis RG, Vishwanatha JK. Altered expression of annexin II in human B-cell lymphoma cell lines. Biochem Biophys Acta. 1996;1313(3):295–301.CrossRefPubMed

19.

Weston-Bell NJ, Hendriks D, Sugiyarto G, Bos NA, Kluin-Nelemans HC, Forconi F, et al. Hairy cell leukemia cell lines expressing annexin A1 and displaying B-cell receptor signals characteristic of primary tumor cells lack the signature BRAF mutation to reveal unrepresentative origins. Leukemia. 2013;27(1):241–5. https://doi.org/10.1038/leu.2012.163.CrossRefPubMed

20.

Handschuh L, Kazmierczak M, Milewski MC, Goralski M, Luczak M, Wojtaszewska M, et al. Gene expression profiling of acute myeloid leukemia samples from adult patients with AML-M1 and -M2 through boutique microarrays, real-time PCR and droplet digital PCR. Int J Oncol. 2018;52(3):656–78. https://doi.org/10.3892/ijo.2017.4233.CrossRefPubMed

21.

Tressler RJ, Yeatman T, Nicolson GL. Extracellular annexin VI expression is associated with divalent cation-dependent endothelial cell adhesion of metastatic RAW117 large-cell lymphoma cells. Exp Cell Res. 1994;215(2):395–400. https://doi.org/10.1006/excr.1994.1358.CrossRefPubMed

22.

Zhang LY, Jiang M, Li X, Shen F, Jia R, Ruan CG. Expression of annexin II in patients with hematologic malignancies. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009;17(3):529–32.PubMed

23.

Kassambara A, Reme T, Jourdan M, Fest T, Hose D, Tarte K, et al. GenomicScape: an easy-to-use web tool for gene expression data analysis. Application to investigate the molecular events in the differentiation of B cells into plasma cells. PLoS Comput Biol. 2015;11(1):e1004077. https://doi.org/10.1371/journal.pcbi.1004077.CrossRefPubMedPubMedCentral

24.

Basso K, Liso A, Tiacci E, Benedetti R, Pulsoni A, Foa R, et al. Gene expression profiling of hairy cell leukemia reveals a phenotype related to memory B cells with altered expression of chemokine and adhesion receptors. J Exp Med. 2004;199(1):59–68. https://doi.org/10.1084/jem.20031175.CrossRefPubMedPubMedCentral

25.

Sadik W, Coupland S, Thachil J. Hairy cell leukaemia, negative for conventional cell markers, diagnosed using antibodies to annexin A1 and T-bet. Br J Haematol. 2010;151(3):207. https://doi.org/10.1111/j.1365-2141.2010.08359.x.CrossRefPubMed

26.

Szczepanek J, Laskowska J, Lewandowska-Bieniek J, Tretyn A, Styczynski J. Array-based genomic and transcriptomic profiling in pediatric acute leukemias in search of genes responsible for cyclophosphamide resistance. Blood. 2014;124(21):3802.

27.

Proto-Siqueira R, Panepucci RA, Careta FP, Lee A, Clear A, Morris K, Owen C, Rizzatti EG, Silva WA Jr, Falcão RP, Zago MA, Gribben JG. SAGE analysis demonstrates increased expression of TOSO contributing to Fas-mediated resistance in CLL. Blood. 2008;112(2):394–7. https://doi.org/10.1182/blood-2007-11-124065.CrossRefPubMedPubMedCentral

28.

Lindberg ML, Haag P, Moshfegh A, Kanter L, Bjorkholm M, Lewensohn R, Kristina V, Stenke L. Gene expression analyses at time of diagnosis indicate biomarkers predictive of therapeutic response in acute myeloid leukemia. Blood. 2013;122(21):2619.

29.

Chitteti BR, Poteat B, Wang M, Liu Y, Srour EF. Genetic and proteomic analysis of functionally distinct human hematopoietic stem cells from bone marrow, mobilized peripheral blood, and cord blood. Blood. 2008;112(11):1324.

30.

Hayhoe RP, Kamal AM, Solito E, Flower RJ, Cooper D, Perretti M. Annexin 1 and its bioactive peptide inhibit neutrophil-endothelium interactions under flow: indication of distinct receptor involvement. Blood. 2006;107(5):2123–30. https://doi.org/10.1182/blood-2005-08-3099.CrossRefPubMed

31.

Tsai WH, Chien HY, Shih CH, Lai SL, Li IT, Hsu SC, et al. Annexin A1 mediates the anti-inflammatory effects during the granulocytic differentiation process in all-trans retinoic acid-treated acute promyelocytic leukemic cells. J Cell Physiol. 2012;227(11):3661–9. https://doi.org/10.1002/jcp.24073.CrossRefPubMed

32.

Bao H, Jiang M, Zhu M, Sheng F, Ruan J, Ruan C. Overexpression of Annexin II affects the proliferation, apoptosis, invasion and production of proangiogenic factors in multiple myeloma. Int J Hematol. 2009;90(2):177–85. https://doi.org/10.1007/s12185-009-0356-8.CrossRefPubMed

33.

Seckinger A, Meissner T, Moreaux J, Depeweg D, Hillengass J, Hose K, et al. Clinical and prognostic role of annexin A2 in multiple myeloma. Blood. 2012;120(5):1087–94. https://doi.org/10.1182/blood-2012-03-415588.CrossRefPubMed

34.

Tumino M, Accordi B, Sciro M, Milani G, Tognazzo F, Giordan M, Kronnie TT, Basso G, Nigro LL. Expression of Annexin 2 in pediatric B-acute lymphoblastic leukemia: a marker of aggressiveness and a potential therapeutic target. Blood. 2009;114(22):2605.

35.

Chang KS, Wang G, Freireich EJ, Daly M, Naylor SL, Trujillo JM, et al. Specific expression of the annexin VIII gene in acute promyelocytic leukemia. Blood. 1992;79(7):1802–10.PubMed

36.

Payton JE, Grieselhuber NR, Chang LW, Murakami MA, Yuan W, Link DC, Nagarajan R, Watson MA, Ley TJ. The expression signature of M3 AML suggests direct and indirect effects of PML-RARA on target genes. Blood. 2007;110(11):719.

37.

Sarkar A, Yang P, Fan YH, Mu ZM, Hauptmann R, Adolf GR, et al. Regulation of the expression of annexin VIII in acute promyelocytic leukemia. Blood. 1994;84(1):279–86.PubMed

38.

Hata H, Tatemichi M, Nakadate T. Involvement of annexin A8 in the properties of pancreatic cancer. Mol Carcinog. 2014;53(3):181–91. https://doi.org/10.1002/mc.21961.CrossRefPubMed

39.

Chao A, Wang TH, Lee YS, Hsueh S, Chao AS, Chang TC, et al. Molecular characterization of adenocarcinoma and squamous carcinoma of the uterine cervix using microarray analysis of gene expression. Int J Cancer. 2006;119(1):91–8. https://doi.org/10.1002/ijc.21813.CrossRefPubMed

40.

Oka R, Nakashiro K, Goda H, Iwamoto K, Tokuzen N, Hamakawa H. Annexin A8 is a novel molecular marker for detecting lymph node metastasis in oral squamous cell carcinoma. Oncotarget. 2016;7(4):4882–9. https://doi.org/10.18632/oncotarget.6639.CrossRefPubMed

41.

Rossetti S, Bshara W, Reiners JA, Corlazzoli F, Miller A, Sacchi N. Harnessing 3D models of mammary epithelial morphogenesis: an off the beaten path approach to identify candidate biomarkers of early stage breast cancer. Cancer Lett. 2016;380(2):375–83. https://doi.org/10.1016/j.canlet.2016.07.003.CrossRefPubMedPubMedCentral

Title: Distinct prognostic values of Annexin family members expression in acute myeloid leukemia
Authors: Y. Niu
X. Yang
Y. Chen
X. Jin
Y. Xie
Y. Tang
L. Li
S. Liu
Y. Guo
X. Li
L. Duan
H. Wang
Publication date: 01-09-2019
Publisher: Springer International Publishing
Keyword: Acute Myeloid Leukemia
Published in: Clinical and Translational Oncology / Issue 9/2019
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-019-02045-7

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Abstract

Background

Methods

Results

Conclusions

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