Correlation between DNMT3a Mutation and Peripheral Blood Cell Count in Adult Primary Acute Myeloid Leukemia: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 SHENKe-feng ¹ , YINChang-xin ¹ , YEYan-yan ¹ ,  JIANGQian-li ¹ , YUANLe-zhong ² , LUYang ²

1. Department of Hematology, NanFang Hospital, Southern Medical University, Guangzhou 510515, China;
2. The First Clinical College of, Southern Medical University, Guangzhou 510515, China;

Corresponding author：

JIANGQian-li, Email: jiangqianlid@gmail.com

Keywords：

DNMT3a mutation; Adult primary acute myeloid leukemia; Peripheral blood cell count; Meta-analysis; Case-control study

DOI：

10.7507/1672-2531.20140039

Video：

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Objective To systematically review the correlation between DNMT3a mutation and peripheral blood cell count on the time of diagnosis for adult primary acute myeloid leukemia (AML). Methods Literature search in the databases such as PubMed, ScienceDirect, EBSCO, Web of Science, CNKI, VIP and WanFang Data was performed to collect the case-control studies about the correlation between the DNMT3a mutations and adult AML up to December 2012. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of the included studies, and then RevMan 5.0 software was conducting for metaanalysis. Results A total of 10 studies involving 2 704 patients were included. The results of meta-analyses showed that:the levels of peripheral blood WBC, HGB and PLT of the DNMT3a-mutated group were significantly higher than those of the DNMT3a-wildtype group for the initial visit of adult primary AML patients (all P values < 0.05). Conclusion The peripheral blood cell counts of the DNMT3a-mutated group are higher than those of the DNMT3a-wildtype group for the initial visit of adult primary AML patients, indicating DNMT3a mutation might contribute to promote cell proliferation, and this helps us better understand the role of DNMT3a mutation in the development of AML.

Citation： SHENKe-feng, YINChang-xin, YEYan-yan, JIANGQian-li, YUANLe-zhong, LUYang. Correlation between DNMT3a Mutation and Peripheral Blood Cell Count in Adult Primary Acute Myeloid Leukemia: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2014, 14(2): 225-230. doi: 10.7507/1672-2531.20140039 Copy

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2.	Chen J, Odenike O, Rowley JD. Leukemogenesis:more than mutant genes. Nat Rev Cancer, 2010, 10(1):23-36.
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17.	Ribeiro AF, Pratcorona M, Erpelinck-Verschueren C, et al. Mutant DNMT3A:a marker of poor prognosis in acute myeloid leukemia. Blood, 2012, 119(24):5824-5831.
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24.	Dehmel U, Zaborski M, Meierhoff G, et al. Effects of FLT3 ligand on human leukemia cells. I. Proliferative response of myeloid leukemia cells. Leukemia, 1996, 10(2):261-270.
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26.	Drexler HG. Expression of FLT3 receptor and response to FLT3 ligand by leukemic cells. Leukemia, 1996, 10(4):588-599.
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28.	Smith CC, Wang Q, Chin CS, et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature, 2012, 485(7397):260-263.
29.	Okamoto M, Hayakawa F, Miyata Y, et al. Lyn is an important component of the signal transduction pathway specific to FLT3/ITD and can be a therapeutic target in the treatment of AML with FLT3/ITD. Leukemia, 2007, 21(3):403-410.
30.	Yan XJ, Chen Z, Chen SJ, et al. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet, 2011, 43(4):309-315.
31.	Grimwade D, Hills RK. Independent prognostic factors for AML outcome. Hematology Am Soc Hematol Educ Program, 2009, 1(1):385-395.

1. Rodríguez-Paredes M, Esteller M. Cancer epigenetics reaches mainstream oncology. Nat Med, 2011, 17(3):330-339.
2. Chen J, Odenike O, Rowley JD. Leukemogenesis:more than mutant genes. Nat Rev Cancer, 2010, 10(1):23-36.
3. Robertson KD. DNA methylation and human disease. Nat Rev Genet, 2005, 6(8):597-610.
4. Okano M, Bell DW, Haber DA, et al. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell, 1999, 99(3):247-257.
5. Trowbridge JJ, Orkin SH. Dnmt3a silences hematopoietic stem cell self-renewal. Nat Genet, 2011, 44(1):13-14.
6. Challen GA, Sun D, Jeong M, et al. Dnmt3a is essential for hematopoietic stem cell differentiation. Nat Genet, 2011, 44(1):23-31.
7. Ley TJ, Ding L, Walter MJ, et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med, 2010, 363(25):2424-2433.
8. Shen Y, Zhu YM, Chen SJ, et al. Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia. Blood, 2011, 118(20):5593-5603.
9. LaRochelle O, Bertoli S, Vergez F, et al. Do AML patients with DNMT3A exon 23 mutations benefit from idarubicin as compared to daunorubicin? A single center experience. Oncotarget, 2011, 2(11):850-861.
10. 乔纯, 孙超, 张苏江, 等.急性髓系白血病中DNMT3a基因突变的研究.中国实验血液学杂志, 2011, 19(2):303-307.
11. Hou HA, Kuo YY, Liu CY, et al. DNMT3A mutations in acute myeloid leukemia:stability during disease evolution and clinical implications. Blood, 2012, 119(2):559-568.
12. Lin J, Yao DM, Qian J, et al. Recurrent DNMT3A R882 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome. PLoS One, 2011, 6(10):e26906.
13. Renneville A, Boissel N, Nibourel O, et al. Prognostic significance of DNA methyltransferase 3A mutations in cytogenetically normal acute myeloid leukemia:a study by the Acute Leukemia French Association. Leukemia, 2012, 26(6):1247-1254.
14. Metzeler KH, Walker A, Geyer S, et al. DNMT3A mutations and response to the hypomethylating agent decitabine in acute myeloid leukemia. Leukemia, 2012, 26(5):1106-1107.
15. Thol F, Damm F, Lüdeking A, et al. Incidence and prognostic influence of DNMT3A mutations in acute myeloid leukemia. J Clin Oncol, 2011, 29(21):2889-2896.
16. Marcucci G, Metzeler KH, et al. Age-related prognostic impact of different types of DNMT3A mutations in adults with primary cytogenetically normal acute myeloid leukemia. J Clin Oncol, 2012, 30(7):742-750.
17. Ribeiro AF, Pratcorona M, Erpelinck-Verschueren C, et al. Mutant DNMT3A:a marker of poor prognosis in acute myeloid leukemia. Blood, 2012, 119(24):5824-5831.
18. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol, 2005, 20(5):13.
19. 曾宪涛, 刘慧, 陈曦, 等. Meta分析系列之四:观察性研究的质量评价工具.中国循证心血管医学杂志, 2012, 4(4):297-299.
20. Shih AH, Abdel-Wahab O, Patel JP, et al. The role of mutations in epigenetic regulators in myeloid malignancies. Nat Rev Cancer, 2012, 12(9):599-612.
21. Dombret H. Gene mutation and AML pathogenesis. Blood, 2011, 118(20):5366-5367.
22. Yamashita Y, Yuan J, Suetake I, et al. Array-based genomic resequencing of human leukemia. Oncogene, 2010, 29(25):3723-3731.
23. Shah MY, Licht JD. DNMT3A mutations in acute myeloid leukemia. Nat Genet, 2011, 43(4):289-290.
24. Dehmel U, Zaborski M, Meierhoff G, et al. Effects of FLT3 ligand on human leukemia cells. I. Proliferative response of myeloid leukemia cells. Leukemia, 1996, 10(2):261-270.
25. Meierhoff G, Dehmel U, Gruss HJ, et al. Expression of FLT3 receptor and FLT3-ligand in human leukemia-lymphoma cell lines. Leukemia, 1995, 9(8):1368-1372.
26. Drexler HG. Expression of FLT3 receptor and response to FLT3 ligand by leukemic cells. Leukemia, 1996, 10(4):588-599.
27. Quentmeier H, Reinhardt J, Zaborski M, et al. FLT3 mutations in acute myeloid leukemia cell lines. Leukemia, 2003, 17(1):120-124.
28. Smith CC, Wang Q, Chin CS, et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature, 2012, 485(7397):260-263.
29. Okamoto M, Hayakawa F, Miyata Y, et al. Lyn is an important component of the signal transduction pathway specific to FLT3/ITD and can be a therapeutic target in the treatment of AML with FLT3/ITD. Leukemia, 2007, 21(3):403-410.
30. Yan XJ, Chen Z, Chen SJ, et al. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet, 2011, 43(4):309-315.
31. Grimwade D, Hills RK. Independent prognostic factors for AML outcome. Hematology Am Soc Hematol Educ Program, 2009, 1(1):385-395.

Chinese Journal of Evidence-Based Medicine

Correlation between DNMT3a Mutation and Peripheral Blood Cell Count in Adult Primary Acute Myeloid Leukemia: A Meta-Analysis

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