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Article

NOTCH1, SF3B1, MDM2 and MYD88 mutations in patients with chronic lymphocytic leukemia

  • Authors:
    • Yosra Maleki
    • Zahra Alahbakhshi
    • Zahra Heidari
    • Mohammad‑Taher Moradi
    • Ziba Rahimi
    • Kheirolah Yari
    • Zohreh Rahimi
    • Mozafar Aznab
    • Meisam Ahmadi‑Khajevand
    • Fariborz Bahremand
  • View Affiliations / Copyright

    Affiliations: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah 67148‑69914, Iran, Department of Internal Medicine, Kermanshah University of Medical Sciences, Kermanshah 67148‑69914, Iran, Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah 67148‑69914, Iran
  • Pages: 4016-4023
    |
    Published online on: February 19, 2019
       https://doi.org/10.3892/ol.2019.10048
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Abstract

Mutations in certain genes have been suggested to be associated with the pathogenesis of chronic lymphocytic leukemia (CLL), which is the most common leukemia in adults. In a case‑control study, 100 patients with CLL and 105 healthy individuals were investigated for Notch homolog 1, translocation‑associated (Drosophila) (NOTCH1) c.7544‑7545delCT, recombinant splicing factor 3B subunit 1 (SF3B1) c.2098A>G, mouse double minute 2 homolog (MDM2) 40‑bp insertion/deletion and myeloid differentiation primary response 88 (MYD88) L265P mutations by using allele specific‑polymerase chain reaction (AS‑PCR), a designed AS‑PCR, PCR and PCR‑restriction fragment length polymorphism methods, respectively. The presence of NOTCH1 and SF3B1 mutations were confirmed by genomic DNA sequencing. The NOTCH1 mutation was detected in 10% of patients and not detected in the control group. A higher frequency of NOTCH1 mutation was detected in patients with stage III CLL (62.5%) compared with stages 0‑II CLL (37.5%) (odds ratio, 4.69‑fold; 95% confidence interval, 1.0‑21.9; P=0.049). The SF3B1 mutation was observed in 12% of the patients compared with 1.9% of the controls (P=0.012). The presence of MDM2 polymorphism was not associated with the risk or the stage of the disease. In addition, the MYD88 L265P mutation was not detected in the patients or the controls. The current study established the frequency of NOTCH1, SF3B1, MDM2 and MYD88 mutations in patients with CLL from the Kurdish population of Western Iran. In summary, a high frequency of NOTCH1 and SF3B1 mutations were identified in patients with CLL compared with healthy individuals, and the NOTCH1 mutation was associated with a high stage of the disease.
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1 

Parikh SA, Rabe KG, Kay NE, Call TG, Ding W, Schwager SM, Bowen DA, Conte M, Jelinek DF, Slager SL and Shanafelt TD: Chronic lymphocytic leukemia in young (≤55 years) patients: A comprehensive analysis of prognostic factors and outcomes. Haematologica. 99:140–147. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Shanafelt TD, Rabe KG, Kay NE, Zent CS, Jelinek DF, Reinalda MS, Schwager SM, Bowen DA, Slager SL, Hanson CA and Call TG: Age at diagnosis and the utility of prognostic testing in patients with chronic lymphocytic leukemia. Cancer. 116:4777–4787. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Ghia P and Hallek M: Management of chronic lymphocytic leukemia. Haematologica. 99:965–972. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Shahjahani M, Mohammadiasl J, Noroozi F, Seghatoleslami M, Shahrabi S, Saba F and Saki N: Molecular basis of chronic lymphocytic leukemia diagnosis and prognosis. Cell Oncol (Dordr). 38:93–109. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Puente XS, Pinyol M, Quesada V, Conde L, Ordóñez GR, Villamor N, Escaramis G, Jares P, Beà S, González-Díaz M, et al: Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature. 475:101–105. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Gianfelici V: Activation of the NOTCH1 pathway in chronic lymphocytic leukemia. Haematologica. 97:328–330. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Sportoletti P, Baldoni S, Del Papa B, Aureli P, Dorillo E, Ruggeri L, Plebani S, Amico V, Di Tommaso A, Rosati E, et al: A revised NOTCH1 mutation frequency still impacts survival while the allele burden predicts early progression in chronic lymphocytic leukemia. Leukemia. 28:436–439. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Landau DA and Wu CJ: Chronic lymphocytic leukemia: Molecular heterogeneity revealed by high-throughput genomics. Genome Med. 5:472013. View Article : Google Scholar : PubMed/NCBI

9 

Wan Y and Wu CJ: SF3B1 mutations in chronic lymphocytic leukemia. Blood. 121:4627–4634. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Dong HJ, Fang C, Fan L, Zhu DX, Wang DM, Zhu HY, Zhuang Y, Miao KR, Liu P, Xu W and Li JY: MDM2 promoter SNP309 is associated with an increased susceptibility to chronic lymphocytic leukemia and correlates with MDM2 mRNA expression in Chinese patients with CLL. Int J Cancer. 130:2054–2061. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Hua W, Zhang A, Duan P, Zhu J, Zhao Y, He J and Zhang Z: MDM2 promoter del1518 polymorphism and cancer risk: Evidence from 22,931 subjects. Onco Targets Ther. 10:3773–3780. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Wang CZ, Lin J, Qian J, Shao R, Xue D, Qian W, Xiao GF, Deng ZQ, Yang J, Li Y and Chen XX: Development of high-resolution melting analysis for the detection of the MYD88 L265P mutation. Clin Biochem. 46:385–387. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Rahimi Z, Vaisi-Raygani A, Mozafari H, Kharrazi H, Rezaei M and Nagel RL: Prevalence of factor V Leiden (G1691A) and prothrombin (G20210A) among Kurdish population from Western Iran. J Thromb Thrombolysis. 25:280–283. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Argentou N, Vassilopoulos G, Ioannou M, Germenis A and Speletas M: Rapid detection of MYD88-L265P mutation by PCR-RFLP in B-cell lymphoproliferative disorders. Leukemia. 28:447–449. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Jafari Y, Rahimi Z, Vaisi-Raygani A and Rezaei M: Interaction of eNOS polymorphism with MTHFR variants increase the risk of diabetic nephropathy and its progression in type 2 diabetes mellitus patients. Mol Cell Biochem. 353:23–34. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Li PP, Feng LL, Chen N, Ge XL, Lv X, Lu K, Ding M, Yuan D and Wang X: Metadherin contributes to the pathogenesis of chronic lymphocytic leukemia partially through Wnt/β-catenin pathway. Med Oncol. 32:4792015. View Article : Google Scholar : PubMed/NCBI

17 

Fabbri G, Rasi S, Rossi D, Trifonov V, Khiabanian H, Ma J, Grunn A, Fangazio M, Capello D, Monti S, et al: Analysis of the chronic lymphocytic leukemia coding genome: Role of NOTCH1 mutational activation. J Exp Med. 208:1389–1401. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Bilous NI, Abramenko IV, Chumak AA, Dyagil IS and Martіna ZV: Detection of NOTCH1 c.7541_7542delCT mutation in chronic lymphocytic leukemia using conventional and real-time polymerase chain reaction. Exp Oncol. 38:112–116. 2016.PubMed/NCBI

19 

Dal Bo M, Pozzo F, Bomben R, Degan M, Marconi D, Zucchetto A, Rossi D, Pozzato G, Zauli G, Gaidano G, et al: ARHGDIA, a mutant TP53-associated Rho GDP dissociation inhibitor, is over-expressed in gene expression profiles of TP53 disrupted chronic lymphocytic leukaemia cells. Br J Haematol. 161:596–599. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Oscier DG, Rose-Zerilli MJ, Winkelmann N, Gonzalez de Castro D, Gomez B, Forster J, Parker H, Parker A, Gardiner A, Collins A, et al: The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial. Blood. 121:468–475. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K, Werner L, Sivachenko A, DeLuca DS, Zhang L, et al: SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med. 365:2497–2506. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Quesada V, Conde L, Villamor N, Ordóñez GR, Jares P, Bassaganyas L, Ramsay AJ, Beà S, Pinyol M, Martínez-Trillos A, et al: Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet. 44:47–52. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Te Raa GD, Derks IA, Navrkalova V, Skowronska A, Moerland PD, van Laar J, Oldreive C, Monsuur H, Trbusek M, Malcikova J, et al: The impact of SF3B1 mutations in CLL on the DNA-damage response. Leukemia. 29:1133–1142. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Sutton LA, Young E, Baliakas P, Hadzidimitriou A, Moysiadis T, Plevova K, Rossi D, Kminkova J, Stalika E, Pedersen LB, et al: Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors. Haematologica. 101:959–967. 2016. View Article : Google Scholar : PubMed/NCBI

25 

Hashemi M, Omrani M, Eskandari-Nasab E, Hasani SS, Mashhadi MA and Taheri M: A 40-bp insertion/deletion polymorphism of Murine Double Minute2 (MDM2) increased the risk of breast cancer in Zahedan, Southeast Iran. Iran Biomed J. 18:245–249. 2014.PubMed/NCBI

26 

Insuasti-Beltran G, Gale JM, Wilson CS, Foucar K and Czuchlewski DR: Significance of MYD88 L265P mutation status in the subclassification of low-grade B-cell lymphoma/leukemia. Arch Pathol Lab Med. 139:1035–1041. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Baliakas P, Hadzidimitriou A, Sutton LA, Rossi D, Minga E, Villamor N, Larrayoz M, Kminkova J, Agathangelidis A, Davis Z, et al: Recurrent mutations refine prognosis in chronic lymphocytic leukemia. Leukemia. 29:329–336. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Jeromin S, Weissmann S, Haferlach C, Dicker F, Bayer K, Grossmann V, Alpermann T, Roller A, Kohlmann A, Haferlach T, et al: SF3B1 mutations correlated to cytogenetics and mutations in NOTCH1, FBXW7, MYD88, XPO1 and TP53 in 1160 untreated CLL patients. Leukemia. 28:108–117. 2014. View Article : Google Scholar : PubMed/NCBI

29 

Rossi D, Rasi S, Spina V, Bruscaggin A, Monti S, Ciardullo C, Deambrogi C, Khiabanian H, Serra R, Bertoni F, et al: Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia. Blood. 121:1403–1412. 2013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Maleki Y, Alahbakhshi Z, Heidari Z, Moradi MT, Rahimi Z, Yari K, Rahimi Z, Aznab M, Ahmadi‑Khajevand M, Bahremand F, Bahremand F, et al: NOTCH1, SF3B1, MDM2 and MYD88 mutations in patients with chronic lymphocytic leukemia. Oncol Lett 17: 4016-4023, 2019.
APA
Maleki, Y., Alahbakhshi, Z., Heidari, Z., Moradi, M., Rahimi, Z., Yari, K. ... Bahremand, F. (2019). NOTCH1, SF3B1, MDM2 and MYD88 mutations in patients with chronic lymphocytic leukemia. Oncology Letters, 17, 4016-4023. https://doi.org/10.3892/ol.2019.10048
MLA
Maleki, Y., Alahbakhshi, Z., Heidari, Z., Moradi, M., Rahimi, Z., Yari, K., Rahimi, Z., Aznab, M., Ahmadi‑Khajevand, M., Bahremand, F."NOTCH1, SF3B1, MDM2 and MYD88 mutations in patients with chronic lymphocytic leukemia". Oncology Letters 17.4 (2019): 4016-4023.
Chicago
Maleki, Y., Alahbakhshi, Z., Heidari, Z., Moradi, M., Rahimi, Z., Yari, K., Rahimi, Z., Aznab, M., Ahmadi‑Khajevand, M., Bahremand, F."NOTCH1, SF3B1, MDM2 and MYD88 mutations in patients with chronic lymphocytic leukemia". Oncology Letters 17, no. 4 (2019): 4016-4023. https://doi.org/10.3892/ol.2019.10048
Copy and paste a formatted citation
x
Spandidos Publications style
Maleki Y, Alahbakhshi Z, Heidari Z, Moradi MT, Rahimi Z, Yari K, Rahimi Z, Aznab M, Ahmadi‑Khajevand M, Bahremand F, Bahremand F, et al: NOTCH1, SF3B1, MDM2 and MYD88 mutations in patients with chronic lymphocytic leukemia. Oncol Lett 17: 4016-4023, 2019.
APA
Maleki, Y., Alahbakhshi, Z., Heidari, Z., Moradi, M., Rahimi, Z., Yari, K. ... Bahremand, F. (2019). NOTCH1, SF3B1, MDM2 and MYD88 mutations in patients with chronic lymphocytic leukemia. Oncology Letters, 17, 4016-4023. https://doi.org/10.3892/ol.2019.10048
MLA
Maleki, Y., Alahbakhshi, Z., Heidari, Z., Moradi, M., Rahimi, Z., Yari, K., Rahimi, Z., Aznab, M., Ahmadi‑Khajevand, M., Bahremand, F."NOTCH1, SF3B1, MDM2 and MYD88 mutations in patients with chronic lymphocytic leukemia". Oncology Letters 17.4 (2019): 4016-4023.
Chicago
Maleki, Y., Alahbakhshi, Z., Heidari, Z., Moradi, M., Rahimi, Z., Yari, K., Rahimi, Z., Aznab, M., Ahmadi‑Khajevand, M., Bahremand, F."NOTCH1, SF3B1, MDM2 and MYD88 mutations in patients with chronic lymphocytic leukemia". Oncology Letters 17, no. 4 (2019): 4016-4023. https://doi.org/10.3892/ol.2019.10048
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