ArticleThe Journal of biological chemistry2011
Aberrant epigenetic and genetic marks are seen in myelodysplastic leukocytes and reveal Dock4 as a candidate pathogenic gene on chromosome 7q.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- HSC commitment-associated epigenetic signature is prognostic in acute myeloid leukemia.The Journal of clinical investigation · 2014Pooled it
- Genome-wide DNA methylation analysis pre- and post-lenalidomide treatment in patients with myelodysplastic syndrome with isolated deletion (5q).Annals of hematology · 2021Trial
- Monosomal karyotype and chromosome 17p loss or TP53 mutations in decitabine-treated patients with acute myeloid leukemia.Annals of hematology · 2020Trial
- Single-cell RNA-seq reveals a distinct transcriptome signature of aneuploid hematopoietic cells.Blood · 2017Trial
- Myeloma is characterized by stage-specific alterations in DNA methylation that occur early during myelomagenesis.Journal of immunology (Baltimore, Md. : 1950) · 2013Trial
- Kmt2c restricts G-CSF-driven HSC mobilization and granulocyte production in a methyltransferase-independent manner.Cell reports · 2024Article
- Potential genetic biomarkers predict adverse pregnancy outcome during early and mid-pregnancy in women with systemic lupus erythematosus.Frontiers in endocrinology · 2022Article
- The Role of Somatic Mutations in Acute Myeloid Leukemia Pathogenesis.Cold Spring Harbor perspectives in medicine · 2021Review
- Recombinant interleukin-2 stimulates lymphocyte recovery in patients with severe COVID-19.Experimental and therapeutic medicine · 2021Article
- Epigenetic modifiers in normal and aberrent erythropoeisis.Seminars in hematology · 2021Review
- Impact of somatic mutations in myelodysplastic patients with isolated partial or total loss of chromosome 7.Leukemia · 2020Article
- Loss of the Fanconi anemia-associated protein NIPA causes bone marrow failure.The Journal of clinical investigation · 2020Article
- Loss of Function of DOCK4 in Myelodysplastic Syndromes Stem Cells is Restored by Inhibitors of DOCK4 Signaling Networks.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Epigenetically Aberrant Stroma in MDS Propagates Disease via Wnt/β-Catenin Activation.Cancer research · 2017Article
- Mutational Landscape and Gene Expression Patterns in Adult Acute Myeloid Leukemias with Monosomy 7 as a Sole Abnormality.Cancer research · 2017Article
- H2AX deficiency is associated with erythroid dysplasia and compromised haematopoietic stem cell function.Scientific reports · 2016Article
- Defective quorum sensing of acute lymphoblastic leukemic cells: evidence of collective behavior of leukemic populations as semi-autonomous aberrant ecosystems.American journal of cancer research · 2016Article
- Reduced DOCK4 expression leads to erythroid dysplasia in myelodysplastic syndromes.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Quantitative Detection of ID4 Gene Aberrant Methylation in the Differentiation of Myelodysplastic Syndrome from Aplastic Anemia.Chinese medical journal · 2015Article
- Functional evidence implicating chromosome 7q22 haploinsufficiency in myelodysplastic syndrome pathogenesis.eLife · 2015Article
Corrections and comments
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Authors and funding
30 authors at 11 institutions in 2 countries.
Funding
Abstract
Myelodysplastic syndromes (MDS) are characterized by abnormal and dysplastic maturation of all blood lineages. Even though epigenetic alterations have been seen in MDS marrow progenitors, very little is known about the molecular alterations in dysplastic peripheral blood cells. We analyzed the methylome of MDS leukocytes by the HELP assay and determined that it was globally distinct from age-matched controls and was characterized by numerous novel, aberrant hypermethylated marks that were located mainly outside of CpG islands and preferentially affected GTPase regulators and other cancer-related pathways. Additionally, array comparative genomic hybridization revealed that novel as well as previously characterized deletions and amplifications could also be visualized in peripheral blood leukocytes, thus potentially reducing the need for bone marrow samples for future studies. Using integrative analysis, potentially pathogenic genes silenced by genetic deletions and aberrant hypermethylation in different patients were identified. DOCK4, a GTPase regulator located in the commonly deleted 7q31 region, was identified by this unbiased approach. Significant hypermethylation and reduced expression of DOCK4 in MDS bone marrow stem cells was observed in two large independent datasets, providing further validation of our findings. Finally, DOCK4 knockdown in primary marrow CD34(+) stem cells led to decreased erythroid colony formation and increased apoptosis, thus recapitulating the bone marrow failure seen in MDS. These findings reveal widespread novel epigenetic alterations in myelodysplastic leukocytes and implicate DOCK4 as a pathogenic gene located on the 7q chromosomal region.
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