Proteomics profiling and genomics computational analysis of acute myeloid leukemia / Md. Mirazul Islam

Md. Mirazul, Islam (2017) Proteomics profiling and genomics computational analysis of acute myeloid leukemia / Md. Mirazul Islam. Masters thesis, Universiti Malaya.

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Abstract

underlying oncogenic transformation mechanisms of a fusion protein (MLL-GAS7), differential expression patterns of growth arrest specific-7 (GAS7) were studied using neuro-2a (N2A) cell line. Levels of C&Ckines in AML plasma differed significantly (p<0.005) between AML patients and healthy controls, in which 13 were upregulated and 4 downregulated. In addition, circulating C&Ckines follow distinct expression patterns that have the potential to be used for subclassification of AML, complementing cytogenetic, genetic, and epigenetic information. Differential expression of ten novel C&Ckines in AML plasma has been demonstrated, which have not been previously reported in AML. Importantly, our results indicated that MPO, MIF, HOF, and Galactin 3 have diagnostic significance. We speculated that MIF and TRAIL are promoting survival of AML blasts using PI3K/Akt pathway through the anti-apoptotic mechanism. DNA methylation is a common epigenetic aberration in AML and we found almost 200 genes hypermethylated in 90% ofTCGA cases. Distinct signatures have been found after combining methylation and mutation (three groups of patients and two groups of genes). For patients with del (5q) positive, average survival was <l year, whereas for T (15; 17) positive patients, there was significantly higher survival rate (> 3 years) in Kaplan-Meier curve. MLL and GAS7 downstream targeted genes expression vary (particularly Hox genes) in AML patients due to fusion protein formation. Notable differences had been noticed in N2A cell line for attachment and plating efficiency as well as growth curve due to expression of GAS7 which is a partner protein of MLL, one of the reported causative factors in AML. In conclusion, C&Ckines expression profile in AML patients differs from normal and forms a distinct pattern of expression. Integrated analysis of genomic, proteomic, and transcriptomics data and regulation of fusion protein expression may reveal insight into the pathogenesis of AML.

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