Epigenetic dysregulation of the erythropoietic transcription factor KLF1 and the β-like globin locus in juvenile myelomonocytic leukemia
Increased levels of fetal hemoglobin (HbF) are a hallmark of more than half of the children diagnosed with juvenile myelomonocytic leukemia (JMML). Elevated HbF levels in JMML are associated with DNA hypermethylation of distinct gene promoter regions in leukemic cells. Since the regulation of globin...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-08-01
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| Series: | Epigenetics |
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| Online Access: | http://dx.doi.org/10.1080/15592294.2017.1356959 |
| _version_ | 1797678950443384832 |
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| author | Silvia Fluhr Christopher Felix Krombholz Angelina Meier Thomas Epting Oliver Mücke Christoph Plass Charlotte M. Niemeyer Christian Flotho |
| author_facet | Silvia Fluhr Christopher Felix Krombholz Angelina Meier Thomas Epting Oliver Mücke Christoph Plass Charlotte M. Niemeyer Christian Flotho |
| author_sort | Silvia Fluhr |
| collection | DOAJ |
| description | Increased levels of fetal hemoglobin (HbF) are a hallmark of more than half of the children diagnosed with juvenile myelomonocytic leukemia (JMML). Elevated HbF levels in JMML are associated with DNA hypermethylation of distinct gene promoter regions in leukemic cells. Since the regulation of globin gene transcription is known to be under epigenetic control, we set out to study the relation of DNA methylation patterns at β-/γ-globin promoters, mRNA and protein expression of globins, and epigenetic modifications of genes encoding the globin-regulatory transcription factors BCL11A and KLF1 in nucleated erythropoietic precursor cells of patients with JMML. We describe several altered epigenetic components resulting in disordered globin synthesis in JMML. We identify a cis-regulatory upstream KLF1 enhancer sequence as highly sensitive to DNA methylation and frequently hypermethylated in JMML. The data indicate that the dysregulation of β-like globin genes is a genuine attribute of the leukemic cell clone in JMML and involves mechanisms not taking part in the normal fetal-to-adult hemoglobin switch. |
| first_indexed | 2024-03-11T23:07:20Z |
| format | Article |
| id | doaj.art-46b22d2d9f224fcfaa035f5003c1a5c6 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:07:20Z |
| publishDate | 2017-08-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-46b22d2d9f224fcfaa035f5003c1a5c62023-09-21T12:43:13ZengTaylor & Francis GroupEpigenetics1559-22941559-23082017-08-0112871572310.1080/15592294.2017.13569591356959Epigenetic dysregulation of the erythropoietic transcription factor KLF1 and the β-like globin locus in juvenile myelomonocytic leukemiaSilvia Fluhr0Christopher Felix Krombholz1Angelina Meier2Thomas Epting3Oliver Mücke4Christoph Plass5Charlotte M. Niemeyer6Christian Flotho7Division of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of FreiburgDivision of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of FreiburgDivision of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of FreiburgClinical Chemistry and Laboratory Medicine, Medical Center, Faculty of Medicine, University of FreiburgDivision of Epigenomics and Cancer Risk Factors, German Cancer Research CenterDivision of Epigenomics and Cancer Risk Factors, German Cancer Research CenterDivision of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of FreiburgDivision of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of FreiburgIncreased levels of fetal hemoglobin (HbF) are a hallmark of more than half of the children diagnosed with juvenile myelomonocytic leukemia (JMML). Elevated HbF levels in JMML are associated with DNA hypermethylation of distinct gene promoter regions in leukemic cells. Since the regulation of globin gene transcription is known to be under epigenetic control, we set out to study the relation of DNA methylation patterns at β-/γ-globin promoters, mRNA and protein expression of globins, and epigenetic modifications of genes encoding the globin-regulatory transcription factors BCL11A and KLF1 in nucleated erythropoietic precursor cells of patients with JMML. We describe several altered epigenetic components resulting in disordered globin synthesis in JMML. We identify a cis-regulatory upstream KLF1 enhancer sequence as highly sensitive to DNA methylation and frequently hypermethylated in JMML. The data indicate that the dysregulation of β-like globin genes is a genuine attribute of the leukemic cell clone in JMML and involves mechanisms not taking part in the normal fetal-to-adult hemoglobin switch.http://dx.doi.org/10.1080/15592294.2017.1356959epigenetic regulationfetal hemoglobinjuvenile myelomonocytic leukemiaklf1 |
| spellingShingle | Silvia Fluhr Christopher Felix Krombholz Angelina Meier Thomas Epting Oliver Mücke Christoph Plass Charlotte M. Niemeyer Christian Flotho Epigenetic dysregulation of the erythropoietic transcription factor KLF1 and the β-like globin locus in juvenile myelomonocytic leukemia Epigenetics epigenetic regulation fetal hemoglobin juvenile myelomonocytic leukemia klf1 |
| title | Epigenetic dysregulation of the erythropoietic transcription factor KLF1 and the β-like globin locus in juvenile myelomonocytic leukemia |
| title_full | Epigenetic dysregulation of the erythropoietic transcription factor KLF1 and the β-like globin locus in juvenile myelomonocytic leukemia |
| title_fullStr | Epigenetic dysregulation of the erythropoietic transcription factor KLF1 and the β-like globin locus in juvenile myelomonocytic leukemia |
| title_full_unstemmed | Epigenetic dysregulation of the erythropoietic transcription factor KLF1 and the β-like globin locus in juvenile myelomonocytic leukemia |
| title_short | Epigenetic dysregulation of the erythropoietic transcription factor KLF1 and the β-like globin locus in juvenile myelomonocytic leukemia |
| title_sort | epigenetic dysregulation of the erythropoietic transcription factor klf1 and the β like globin locus in juvenile myelomonocytic leukemia |
| topic | epigenetic regulation fetal hemoglobin juvenile myelomonocytic leukemia klf1 |
| url | http://dx.doi.org/10.1080/15592294.2017.1356959 |
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