Genome wide characterization of minimally differentiated acute myeloid leukemia

Gomes e Silva, F.P.

Minimally differentiated acute myeloid leukemia (AML-M0) occurs in 5 percent of all AML cases as has a remarkably poor prognosis. The aim of this thesis was to characterize a cohort of AML-M0 cases at the genomic and gene expression level making use of single nucleotide polymorphism (SNP) analysis and gene expression profiling, among other techniques. In short, our study contributed in establishing RUNX1 biallelic mutations as a primary event in AML-M0 and showed that homozygosity of RUNX1 mutations was associated with uniparental disomy. We also showed that ETV6 mutation occurs in a small proposition of cases and detected a broad number of RUNX1/ETV6 collaborating mutations, most of which in members of the RAS signaling pathway. In addition, the results suggest that the association between RUNX1 mutation and trisomy 13, and concomitant increased in FLT3 expression, is an alternative way of activatin g the RAS signaling pathway. Finally, gene expression profiling (GEP) showed a...Show moreMinimally differentiated acute myeloid leukemia (AML-M0) occurs in 5 percent of all AML cases as has a remarkably poor prognosis. The aim of this thesis was to characterize a cohort of AML-M0 cases at the genomic and gene expression level making use of single nucleotide polymorphism (SNP) analysis and gene expression profiling, among other techniques. In short, our study contributed in establishing RUNX1 biallelic mutations as a primary event in AML-M0 and showed that homozygosity of RUNX1 mutations was associated with uniparental disomy. We also showed that ETV6 mutation occurs in a small proposition of cases and detected a broad number of RUNX1/ETV6 collaborating mutations, most of which in members of the RAS signaling pathway. In addition, the results suggest that the association between RUNX1 mutation and trisomy 13, and concomitant increased in FLT3 expression, is an alternative way of activatin g the RAS signaling pathway. Finally, gene expression profiling (GEP) showed a distinct expression for AML-M0 cases which indicates they are a distinct entity from other AML groups. GEP also showed that AML-M0 is further subdivided into two distinct subgroups. One of these subgroups was associated with RUNX1 mutations and characterized by the expression of B-lymphocyte related genes.Show less

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Genome wide characterization of minimally differentiated acute myeloid leukemia

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