Abstract
Erythroid Krüppel-like Factor (EKLF/KLF1) is an erythroid-enriched transcription factor that plays a global role in all aspects of erythropoiesis, including cell cycle control and differentiation. We queried whether its mutation might play a role in red cell malignancies by genomic sequencing of the KLF1 transcription unit in cell lines, erythroid neoplasms, dysplastic disorders, and leukemia. In addition, we queried published databases from a number of varied sources. In all cases we only found changes in commonly notated SNPs. Our results suggest that if there are mutations in KLF1 associated with erythroid malignancies, they are exceedingly rare.
Highlights
Erythroid Krüppel-like Factor (EKLF/KLF1) is a red cell-enriched, zinc finger DNA binding protein that interacts with its cognate 5′CCMCRCCCN3′ element at target promoters and enhancers[1]
Perusal of the data enable us to extract the ones most relevant to KLF1 as summarized in Table 1, suggesting these KLF1 gene variants are significantly associated with altered MCH, MCV, and MCHC red cell indices, and RBC and RET numbers
In combination with studies summarized in the Introduction, we felt justified to address whether mutagenic changes in KLF1 might be associated with aberrant or malignant red cell parameters
Summary
Erythroid Krüppel-like Factor (EKLF/KLF1) is a red cell-enriched, zinc finger DNA binding protein that interacts with its cognate 5′CCMCRCCCN3′ element at target promoters and enhancers[1]. Specific functional properties and expression characteristics of EKLF, along with recognition of its surprisingly broad role prior to and during red cell differentiation (reviewed in4–8), provide the conceptual basis for the present study. Subtle altering of EKLF cellular levels can change the erythroid cell cycle status from proliferation to differentiation, an effect mediated, at least in part, by its direct activation of the p21, p18, p27, and E2f2 genes[13,14,15,16,17]. Recognition of a novel target DNA sequence by Nan-EKLF leads to ectopic expression of genes not normally expressed in the red cell, yielding a neomorphic phenotype with cellular and systemic consequences[32,33]
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