Top

Indian Journal of Hematology and Blood Transfusion

Published in:

05-08-2021 | Acute Myeloid Leukemia | Original Article

The Prognostic Significance of the BIN1 and CCND2 Gene in Adult Patients with Acute Myeloid Leukemia

Authors: Xinwen Zhang, Hao Xiong, Jialin Duan, Xiaomin Chen, Yang Liu, Chunlan Huang

Published in: Indian Journal of Hematology and Blood Transfusion | Issue 3/2022

Abstract

Objective

To investigate the expression and clinical significance of Bridging INtegrator 1 (BIN1) and cyclin D2 (CCND2) in newly diagnosed cytogenetically heterogenous adult acute myeloid leukemia patients. Methods Real-time quantitative PCR (RQ-PCR) was used to detect the expression of BIN1 and CCND2 genes in 49 newly diagnosed adult patients with AML, and their clinical significance was analyzed. Results BIN1 and CCND2 genes are highly expressed in patients with AML, which suggest their potential as molecular markers. A statistical significant correlation was found between BIN1 expression with bone marrow blasts (P = 0.012), CD34 expression (P = 0.026), NLR (P = 0.019) and Karyotype risk (P = 0.005). There was a statistically significant correlation between CCND2 and age (P = 0.001), NLR (P = 0.046) Karyotype risk (P = 0.033). The expression level of BIN1 was related to early treatment response (CR or not) (P = 0.043). CCND2 expression was significantly correlated with overall survival (P = 0.013), but not with CR (P = 0.731). Conclusion BIN1 and CCND2 genes are highly expressed in patients with AML, suggesting the potential of these two genes as molecular markers. Moreover, high levels of CCND2 are associated with better prognosis, suggesting the possibility of these two genes as prognostic markers.

Siegel RL, Miller KD (2019) Jemal A (2019) Cancer statistics. CA Cancer J Clin 69(1):7–34. https://doi.org/10.3322/caac.21551CrossRefPubMed

Green CL, Koo KK, Hills RK et al (2010) Prognostic significance of CEBPA mutations in a large cohort of younger adult patients with acute myeloid leukemia: impact of double CEBPA mutations and the interaction with FLT3 and NPM1 mutations. J Clin Oncol 28(16):2739–2747. https://doi.org/10.1200/jco.2009.26.2501CrossRefPubMed

Pyndiah S, Tanida S, Ahmed KM et al (2011) c-MYC suppresses BIN1 to release poly (ADP-ribose) polymerase 1: a mechanism by which cancer cells acquire cisplatin resistance. Sci Signal 4(166):ra19. https://doi.org/10.1126/scisignal.2001556CrossRefPubMed

Elliott K, Ge K, Du W et al (2000) The c-Myc-interacting adaptor protein Bin1 activates a caspase-independent cell death program. Oncogene 19(41):4669–4684. https://doi.org/10.1038/sj.onc.1203681CrossRefPubMed

Muller AJ, Baker JF, DuHadaway JB et al (2003) Targeted disruption of the murine Bin1/Amphiphysin II gene does not disable endocytosis but results in embryonic cardiomyopathy with aberrant myofibril formation. Mol Cell Biol 23(12):4295–4306. https://doi.org/10.1128/MCB.23.12.4295-4306.2003CrossRefPubMedPubMedCentral

Esmailzadeh S, Huang Y, Su MW et al (2015) BIN1 tumor suppressor regulates Fas/Fas ligand-mediated apoptosis through c-FLIP in cutaneous T-cell lymphoma. Leukemia 29(6):1402–1413. https://doi.org/10.1038/leu.2015.9CrossRefPubMed

Wang X, Wang J, Jia Y et al (2017) Methylation decreases the Bin1 tumor suppressor in ESCC and restoration by decitabine inhibits the epithelial mesenchymal transition. Oncotarget 8(12):19661–19673. https://doi.org/10.18632/oncotarget.14914CrossRefPubMedPubMedCentral

Jia Y, Wang H, Wang Y et al (2015) Low expression of Bin1, along with high expression of IDO in tumor tissue and draining lymph nodes, are predictors of poor prognosis for esophageal squamous cell cancer patients. Int J Cancer 137(5):1095–1106. https://doi.org/10.1002/ijc.29481CrossRefPubMed

Wang J, Jia Y, Zhao S et al (2017) BIN1 reverses PD-L1-mediated immune escape by inactivating the c-MYC and EGFR/MAPK signaling pathways in non-small cell lung cancer. Oncogene 36(45):6235–6243. https://doi.org/10.1038/onc.2017.217CrossRefPubMed

10.

Ge Y, Schuster MB, Pundhir S et al (2019) The splicing factor RBM25 controls MYC activity in acute myeloid leukemia. Nat Commun 10(1):172. https://doi.org/10.1038/s41467-018-08076-yCrossRefPubMedPubMedCentral

11.

Zhu C, Shao P, Bao M et al (2014) miR-154 inhibits prostate cancer cell proliferation by targeting CCND2. Urol Oncol 32(1):31.e9-31.e16. https://doi.org/10.1016/j.urolonc.2012.11.013CrossRef

12.

Zhou J, Tian Y, Li J et al (2013) miR-206 is down-regulated in breast cancer and inhibits cell proliferation through the up-regulation of cyclinD2. Biochem Biophys Res Commun 433(2):207–212. https://doi.org/10.1016/j.bbrc.2013.02.084CrossRefPubMed

13.

Du X, Lin LI, Zhang L et al (2015) microRNA-195 inhibits the proliferation, migration and invasion of cervical cancer cells via the inhibition of CCND2 and MYB expression. Oncol Lett 10(4):2639–2643. https://doi.org/10.3892/ol.2015.3541CrossRefPubMedPubMedCentral

14.

Faber ZJ, Chen X, Gedman AL et al (2016) The genomic landscape of core-binding factor acute myeloid leukemias. Nat Genet 48(12):1551–1556. https://doi.org/10.1038/ng.3709CrossRefPubMedPubMedCentral

15.

Eisfeld AK, Kohlschmidt J, Schwind S et al (2017) Mutations in the CCND1 and CCND2 genes are frequent events in adult patients with t(8;21)(q22;q22) acute myeloid leukemia. Leukemia 31(6):1278–1285. https://doi.org/10.1038/leu.2016.332CrossRefPubMed

16.

Martinez-Soria N, McKenzie L, Draper J et al (2018) The oncogenic transcription factor RUNX1/ETO corrupts cell cycle regulation to drive leukemic transformation. Cancer Cell 34(4):626-642.e8. https://doi.org/10.1016/j.ccell.2018.08.015CrossRefPubMedPubMedCentral

17.

Liu W, Yi JM, Liu Y et al (2021) CDK6 Is a potential prognostic biomarker in acute myeloid leukemia. Front Genet 11:600227. https://doi.org/10.3389/fgene.2020.600227CrossRefPubMedPubMedCentral

18.

Raeisi Shahraki H, Bemani P, Jalali M (2017) Classification of bladder cancer patients via penalized linear discriminant analysis. Asian Pac J Cancer Prev 18(5):1453–1457. https://doi.org/10.22034/APJCP.2017.18.5.1453CrossRefPubMed

19.

Vincenzi B, Stacchiotti S, Collini P et al (2017) Human equilibrative nucleoside transporter 1 gene expression is associated with gemcitabine efficacy in advanced leiomyosarcoma and angiosarcoma. Br J Cancer 117(3):340–346. https://doi.org/10.1038/bjc.2017.187CrossRefPubMedPubMedCentral

20.

Pan K, Liang XT, Zhang HK et al (2012) Characterization of bridging integrator 1 (BIN1) as a potential tumor suppressor and prognostic marker in hepatocellular carcinoma. Mol Med 18(1):507–518. https://doi.org/10.2119/molmed.2011.00319CrossRefPubMedPubMedCentral

21.

Tanida S, Mizoshita T, Ozeki K et al (2012) Mechanisms of cisplatin-induced apoptosis and of cisplatin sensitivity: potential of BIN1 to act as a potent predictor of cisplatin sensitivity in gastric cancer treatment. Int J Surg Oncol 2012:862879. https://doi.org/10.1155/2012/862879CrossRefPubMedPubMedCentral

22.

Sun CC, Zhang L, Li G et al (2017) The lncRNA PDIA3P interacts with miR-185-5p to modulate oral squamous cell carcinoma progression by targeting cyclin D2. Mol Ther Nucleic Acids 9:100–110. https://doi.org/10.1016/j.omtn.2017.08.015CrossRefPubMedPubMedCentral

23.

Wang Y, Xue J, Kuang H et al (2017) microRNA-1297 inhibits the growth and metastasis of colorectal cancer by suppressing cyclin D2 expression. DNA Cell Biol 36(11):991–999. https://doi.org/10.1089/dna.2017.3829CrossRefPubMed

24.

Takano Y, Kato Y, van Diest PJ et al (2000) Cyclin D2 overexpression and lack of p27 correlate positively and cyclin E inversely with a poor prognosis in gastric cancer cases. Am J Pathol 156(2):585–594. https://doi.org/10.1016/S0002-9440(10)64763-3CrossRefPubMedPubMedCentral

25.

Sicinski P, Donaher JL, Geng Y et al (1996) Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis. Nature 384(6608):470–474. https://doi.org/10.1038/384470a0CrossRefPubMed

26.

Chen BB, Glasser JR, Coon TA et al (2012) F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation. Blood 119(13):3132–3141. https://doi.org/10.1182/blood-2011-06-358911CrossRefPubMedPubMedCentral

27.

Swart LE, Heidenreich O (2021) The RUNX1/RUNX1T1 network: translating insights into therapeutic options. Exp Hematol 94:1–10. https://doi.org/10.1016/j.exphem.2020.11.005CrossRefPubMedPubMedCentral

28.

Hans CP, Weisenburger DD, Greiner TC et al (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103(1):275–282. https://doi.org/10.1182/blood-2003-05-1545CrossRefPubMed

29.

Mermelshtein A, Gerson A, Walfisch S et al (2005) Expression of D-type cyclins in colon cancer and in cell lines from colon carcinomas. Br J Cancer 93(3):338–345. https://doi.org/10.1038/sj.bjc.6602709CrossRefPubMedPubMedCentral

30.

He X, Chen SY, Yang Z et al (2018) miR-4317 suppresses non-small cell lung cancer (NSCLC) by targeting fibroblast growth factor 9 (FGF9) and cyclin D2 (CCND2). J Exp Clin Cancer Res 37(1):230. https://doi.org/10.1186/s13046-018-0882-4CrossRefPubMedPubMedCentral

31.

Ko E, Kim Y, Park SE et al (2012) Reduced expression of cyclin D2 is associated with poor recurrence-free survival independent of cyclin D1 in stage III non-small cell lung cancer. Lung Cancer 77(2):401–406. https://doi.org/10.1016/j.lungcan.2012.03.027CrossRefPubMed

32.

Sarkar R, Hunter IA, Rajaganeshan R et al (2010) Expression of cyclin D2 is an independent predictor of the development of hepatic metastasis in colorectal cancer. Colorectal Dis 12(4):316–323. https://doi.org/10.1111/j.1463-1318.2009.01829.xCrossRefPubMed

33.

Matsubayashi H, Sato N, Fukushima N et al (2003) Methylation of cyclin D2 is observed frequently in pancreatic cancer but is also an age-related phenomenon in gastrointestinal tissues. Clin Cancer Res 9(4):1446–1452PubMed

34.

Evron E, Umbricht CB, Korz D et al (2001) Loss of cyclin D2 expression in the majority of breast cancers is associated with promoter hypermethylation. Cancer Res 61(6):2782–2787PubMed

35.

Ahmadzada T, Lee K, Clarke C et al (2019) High BIN1 expression has a favorable prognosis in malignant pleural mesothelioma and is associated with tumor infiltrating lymphocytes. Lung Cancer 130:35–41. https://doi.org/10.1016/j.lungcan.2019.02.005CrossRefPubMed

36.

Fang X, Chen C, Xia F et al (2016) CD274 promotes cell cycle entry of leukemia-initiating cells through JNK/Cyclin D2 signaling. J Hematol Oncol 9(1):124. https://doi.org/10.1186/s13045-016-0350-6CrossRefPubMedPubMedCentral

Title: The Prognostic Significance of the BIN1 and CCND2 Gene in Adult Patients with Acute Myeloid Leukemia
Authors: Xinwen Zhang
Hao Xiong
Jialin Duan
Xiaomin Chen
Yang Liu
Chunlan Huang
Publication date: 05-08-2021
Publisher: Springer India
Keyword: Acute Myeloid Leukemia
Published in: Indian Journal of Hematology and Blood Transfusion / Issue 3/2022
Print ISSN: 0971-4502
Electronic ISSN: 0974-0449
DOI: https://doi.org/10.1007/s12288-021-01479-w

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objective

Please log in to get access to this content

Other articles of this Issue 3/2022

Programmed Cell Death Ligand 1 Expression Level and Prognostic Significance in Acute Myeloid Leukemia

Cardiac MRI for Iron Overload in pediatric thalassemia patients– Right Age to Start in a Resource Constrained Environment

Splenectomy in İmmune Thrombocytopenia: A Retrospective Analysis of 25-Year Follow-up Data from a Tertiary Health Clinic

Anti-D Alloimmunization After RhD Positive Red Cell Transfusion to Selected RhD Negative Patients

The Clinical Characteristics and Prognosis of Chinese Patients with Light-Chain Amyloidosis: A Retrospective Multicenter Analysis

Baricitinib: Two Birds with One Stone

Keynote webinar | Spotlight on antibody–drug conjugates in cancer