Bui Thuy Huong, Trinh Le Phuong, Pham Bao Yen

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Abstract: Acute myeloid leukemia (AML) is caused by mutations leading to the loss of control over the proliferation and differentiation of leukocytes in the bone marrow. In Vietnam, studies focusing on the statistics, types, rate and molecular characteristics of common genetic mutations in AML patients are still limited. Identification of chromosomal mutation using the standard karyotyping techniques has assisted effectively AML diagnosis, however, in approximate 45% of AML cases, karyotyping analysis show normal cytogenesis due to abnormalities occurring at the molecular level.In this study, we focused on the establishment of a procedureto detect CCATT-enhancer binding protein α mutations in Transactivation domain region (CEBPA-TAD), which are considered poor prognostic factor for treatment. Using this procedure, one sample carrying a 17-nucleotide deletion in TAD1 domain resulting in a frameshift and a premature stop, was identified and confirmed by sequencing. From these results, we aim to continue screening a larger sample size to get more significant statistical data and investigate the correlation of CEBPA mutation status with clinical characteristic to assist prognosis and treatment. 

Keywords: Acute myeloid leukemia (AML), CCAAT enhancer binding protein α (CEBPA), mutation.


[1] Mrózek K., Marcucci G., Paschka P., Whitman S. P. and Bloomfield C.D., “Clinical relevance of mutations and gene-expressionchanges in adult acute myeloid leukemia with normalcytogenetics: are we ready for a prognostically prioritizedmolecular classification?”, Blood, 100(2), (2007), 431.
[2] Slovak M. L., Kopecky K. J., Cassileth P. A., Harrington D. H., Theil K. S., Mohamed A., Paietta E., Willman C. L., Head D. R., RoweJ. M., Forman S. J. and Appelbaum F. R., “Karyotypicanalysis predicts outcome of preremission and postremissiontherapy in adult acute myeloid leukemia: a Southwest OncologyGroup/Eastern Cooperative Oncology Group Study”, Blood,96(13),(2000), 4075.
[3] Benthaus T., Schneider F., Mellert G., Zellmeier E., Schneider S., Kakadia P. M., Hiddemann W., Bohlander S. K., Feuring-Buske M., Braess J., Spiekermann K., Dufour A.,“Rapid and sensitive screening for CEBPAmutations in acute myeloid leukaemia”, British Journal of Haematology, 143(2), (2008), 230.
[4] Lin L. I., Chen C. Y., Lin D. T., Tsay W., Tang J. L., Yeh Y. C., Shen H. L., Su F. H., Yao M., Huang S. Y., Tien H. F., “Characterization of CEBPA mutations in Acute myeloid leukemia: Most patients with CEBPA mutations have biallelic mutations and show a distinct immunophenotype of the leukemic cells”, Clin Cancer Res, 11(4), (2005), 1372.
[5] Wen X. M., Lin J., Yang J., Yao D. M., Deng Z. Q., Tang C. Y., Xiao G. F., Yang L., Ma J. C., Hu J. B., Qian W., Qian J., “Double CEBPA mutations are prognostically favorable in non-M3 acute myeloid leukemia patients with wild-type NPM1 and FLT3-ITD”, International Journal of Clinical and. Experimental Pathology7(10), (2014), 6832.
[6] Pabst T., Mueller B. U., Zhang P., Radomska H. S., Narravula S., Schnittger S., Behre G., Hiddemann W., Tenen D.G., “Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein-alpha (C/EBPalpha), in acute myeloid leukemia”, Nature Genetics, 27(3), (2001), 70.
[7] Pabst T., Eyholzer M.,Fos J., Mueller B. U.,“Heterogeneity within AML with CEBPA mutations; only CEBPA double mutations, but not single CEBPA mutations are associated with favourable prognosis”, British Journal of cancer, 100(8), (2009), 1343.
[8] Jensen M. A., Fukushima M., Davis R. W., “DMSO and Betaine Greatly Improve Amplification of GC-Rich Constructs in De Novo Synthesis”, Journal.pone, 5(6), (2010), 11024.
Green C. L., Koo K. K., Hills R. K., Burnett A. K., Linch D. C., Gale R. E.,“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”, Journal of Clinical Oncology, 28(16), (2010), 47.