The Effects of Increased Expression of DLK1 Gene on the Pathogenesis of Myelodysplastic Syndromes
ABSTRACT To study the potential role of Delta-like-1 (DLK1) in myelodysplastic syndromes (MDS), we carried out a series of experiments and found that DLK1 mRNA levels are dysregulated in patients with MDS or acute myelogenous leukemia (AML), and its overexpression leads to dysfunction of 32D and 3T3 cells. We conclude that DLK1 dysfunction may contribute to abnormal hematopoiesis of MDS and may be 1 of the antioncogenes. Delta-like-1 (DLK1) is frequently expressed at elevated levels in CD34(+) cells from patients with MDS. To investigate its role in the pathogenesis of MDS, we tested bone marrow samples from a panel of patients with MDS, AML, or myeloproliferative neoplasms, with real-time polymerase chain reaction (PCR). We show here that DLK1 mRNA levels are higher in MDS patients and lower in AML patients than in healthy individuals. Myeloid progenitor 32D cells overexpressing DLK1 display increased apoptosis, reduced differentiation, and decreased cell number expansion, which is also accompanied by changes in cell cycle progression. Immortalized fibroblastic 3T3 cells can grow into tumors in nude mice but the size of tumors are smaller from those overexpressing DLK1. These observations suggest that DLK1 dysfunction may contribute to the ineffective hematopoiesis of MDS.
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ABSTRACT: DLK1-DIO3 represents an imprinted cluster which genes are involved in physiological cell biology as early as the stem cell level and in the pathogenesis of several diseases. Transcription factor-mediated induced pluripotent cells (iPSCs) are considered an unlimited source of patient-specific hematopoietic stem cells for clinical application in patient-tailored regenerative medicine. However, to date there is no marker established able to distinguish embryonic stem cell-equivalent iPSCs or safe human iPSCs. Recent findings suggest that the DLK1-DIO3 locus possesses the potential to represent such a marker but there are also contradictory data. This review aims to report the current data on the topic describing both sides of the coin.Cellular and Molecular Life Sciences CMLS 08/2014; 71(22). DOI:10.1007/s00018-014-1698-9 · 5.86 Impact Factor