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Acute myeloid leukemia and transcription factors: role of erythroid Krüppel-like factor (EKLF)

DOI: 10.1186/1475-2867-12-25

Keywords: Acute myeloid leukemia, Transcription factors, EKLF, GATA1, GATA2, cMPL, FLT3, NPM1, CEBPA mutations

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Abstract:

We evaluated GATA binding protein 1 (GATA1), GATA binding protein 2 (GATA2), EKLF and Myeloproliferative Leukemia virus oncogen homology (cMPL) gene mRNA expression in the bone marrow of 65 AML patients at diagnosis, and assessed any correlation with NPM1, FLT3 and CEBPA mutations. EKLF-positive AML was associated with lower WBC in peripheral blood (P?=?0.049), a higher percentage of erythroblasts in bone marrow (p?=?0.057), and secondary AMLs (P?=?0.036). High expression levels of EKLF showed a trend to association with T-cell antigen expression, such as CD7 (P?=?0.057). Patients expressing EKLF had longer Overall Survival (OS) and Event Free Survival (EFS) than those patients not expressing EKLF (median OS was 35.61 months and 19.31 months, respectively, P?=?0.0241; median EFS was 19.80 months and 8.03 months, respectively, P?=?0.0140). No correlation of GATA1, GATA2, EKLF and cMPL levels was observed with FLT-3 or NPM1 mutation status. Four of four CEBPA mutated AMLs were EKLF positive versus 10 of 29 CEBPA wild-type AMLs; three of the CEBPA mutated, EKLF-positive AMLs were also GATA2 positive. There were no cases of CEBPA mutations in the EKLF-negative AML group. In conclusion, we have validated EKLF mRNA expression as an independent predictor of outcome in AML, and its expression is not associated with FLT3-ITD and NPM1 mutations. EKLF mRNA expression in AML patients may correlate with dysregulated CEBPA.Functional disturbance of transcription factors involved in normal erythroid and megakaryocytic development, such as GATA binding protein 1 (GATA1), GATA binding protein 2 (GATA2), Erythroid Krüppel-like Factor (EKLF) and Myeloproliferative Leukemia virus oncogen homology (c-MPL), is frequent in acute myeloid leukemia (AML), but the role of these disturbances in AML subtypes is unknown.EKLF is a transcription factor that plays a critical role in erythroid cell differentiation. It activates adult hemoglobin through a highly conserved CACCC motif, known to mutate

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