Effect of DLK1 on Tumorigenesis in CD34CD38 Bone Marrow Cells in Myelodysplastic Syndromes

Overview

Journal Oncol Lett

Specialty Oncology

Date 2013 Aug 16

PMID 23946804

Citations 5

Authors

Wei Zhang

Zonghong Shao

Rong Fu

Huaquan Wang

Lijuan Li

Lanzhu Yue

Affiliations

Soon will be listed here.

Abstract

The myelodysplastic syndromes (MDSs) are a group of clonal stem cell disorders resulting from aberrations within hematopoietic stem cells (HSCs), which may lead to the onset of a number of diseases, including acute myeloid leukemia (AML). Recent studies have demonstrated that the expression levels of the DLK1 gene are increased in MDS. In order to determine whether the addition of DLK1 affects tumorigenesis, small interfering (si)RNAs were designed to target DLK1 in order to knockdown its expression in CD34CD38 bone marrow cells in MDS. A lower proliferative rate was observed in the CD34CD38 bone marrow cells following this knockdown of DLK1 expression. The suppression of DLK1 expression resulted in a less aggressive MDS phenotype, which suggests that the upregulation of DLK1 expression may play an oncogenic role in CD34+CD38 bone marrow cells.

Citing Articles

Perturbed epigenetic transcriptional regulation in AML with IDH mutations causes increased susceptibility to NK cells.

Palau A, Segerberg F, Lidschreiber M, Lidschreiber K, Naughton A, Needhamsen M Leukemia. 2023; 37(9):1830-1841.

PMID: 37495775 PMC: 10457197. DOI: 10.1038/s41375-023-01972-3.

Prenatal notch1 receptor blockade by protein delta homolog 1 (DLK1) modulates adipocyte size in vivo.

Kilian T, Kloting N, Bluher M, Beck-Sickinger A Int J Obes (Lond). 2015; 40(4):698-705.

PMID: 26499442 DOI: 10.1038/ijo.2015.227.

Serum DLK1 is a potential prognostic biomarker in patients with hepatocellular carcinoma.

Li H, Cui M, Chen T, Xie H, Cui Y, Tu H Tumour Biol. 2015; 36(11):8399-404.

PMID: 26018510 DOI: 10.1007/s13277-015-3607-8.

Imprinted genes in myeloid lineage commitment in normal and malignant hematopoiesis.

Benetatos L, Vartholomatos G Leukemia. 2015; 29(6):1233-42.

PMID: 25703588 DOI: 10.1038/leu.2015.47.

DLK1-DIO3 imprinted cluster in induced pluripotency: landscape in the mist.

Benetatos L, Vartholomatos G, Hatzimichael E Cell Mol Life Sci. 2014; 71(22):4421-30.

PMID: 25098353 PMC: 11113449. DOI: 10.1007/s00018-014-1698-9.

References

Corey S, Minden M, Barber D, Kantarjian H, Wang J, Schimmer A . Myelodysplastic syndromes: the complexity of stem-cell diseases. Nat Rev Cancer. 2007; 7(2):118-29. DOI: 10.1038/nrc2047. View

Floridon C, Jensen C, Thorsen P, Nielsen O, Sunde L, Westergaard J . Does fetal antigen 1 (FA1) identify cells with regenerative, endocrine and neuroendocrine potentials? A study of FA1 in embryonic, fetal, and placental tissue and in maternal circulation. Differentiation. 2000; 66(1):49-59. DOI: 10.1046/j.1432-0436.2000.066001049.x. View

Laborda J . The role of the epidermal growth factor-like protein dlk in cell differentiation. Histol Histopathol. 2000; 15(1):119-29. DOI: 10.14670/HH-15.119. View

Sakajiri S, OKelly J, Yin D, Miller C, Hofmann W, Oshimi K . Dlk1 in normal and abnormal hematopoiesis. Leukemia. 2005; 19(8):1404-10. DOI: 10.1038/sj.leu.2403832. View

Kim Y . Effect of retinoic acid and delta-like 1 homologue (DLK1) on differentiation in neuroblastoma. Nutr Res Pract. 2010; 4(4):276-82. PMC: 2933444. DOI: 10.4162/nrp.2010.4.4.276. View

Astuti D, Latif F, Wagner K, Gentle D, Cooper W, Catchpoole D . Epigenetic alteration at the DLK1-GTL2 imprinted domain in human neoplasia: analysis of neuroblastoma, phaeochromocytoma and Wilms' tumour. Br J Cancer. 2005; 92(8):1574-80. PMC: 2362015. DOI: 10.1038/sj.bjc.6602478. View

Li L, Forman S, Bhatia R . Expression of DLK1 in hematopoietic cells results in inhibition of differentiation and proliferation. Oncogene. 2005; 24(27):4472-6. DOI: 10.1038/sj.onc.1208637. View

Pellagatti A, Cazzola M, Giagounidis A, Malcovati L, Della Porta M, Killick S . Gene expression profiles of CD34+ cells in myelodysplastic syndromes: involvement of interferon-stimulated genes and correlation to FAB subtype and karyotype. Blood. 2006; 108(1):337-45. DOI: 10.1182/blood-2005-12-4769. View

Hofmann W, de Vos S, Komor M, Hoelzer D, Wachsman W, Koeffler H . Characterization of gene expression of CD34+ cells from normal and myelodysplastic bone marrow. Blood. 2002; 100(10):3553-60. DOI: 10.1182/blood.V100.10.3553. View

10.

Vardiman J, Thiele J, Arber D, Brunning R, Borowitz M, Porwit A . The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009; 114(5):937-51. DOI: 10.1182/blood-2009-03-209262. View

11.

Moore K, Pytowski B, Witte L, Hicklin D, Lemischka I . Hematopoietic activity of a stromal cell transmembrane protein containing epidermal growth factor-like repeat motifs. Proc Natl Acad Sci U S A. 1997; 94(8):4011-6. PMC: 20559. DOI: 10.1073/pnas.94.8.4011. View

12.

Nimer S . MDS: a stem cell disorder--but what exactly is wrong with the primitive hematopoietic cells in this disease?. Hematology Am Soc Hematol Educ Program. 2008; :43-51. DOI: 10.1182/asheducation-2008.1.43. View

13.

Khoury H, Suarez-Saiz F, Wu S, Minden M . An upstream insulator regulates DLK1 imprinting in AML. Blood. 2010; 115(11):2260-3. DOI: 10.1182/blood-2009-03-212746. View