Phosphorylation-mediated EZH2 inactivation promotes drug resistance in multiple myeloma

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Phosphorylation-mediated EZH2 inactivation promotes drug resistance in multiple myeloma.

Alterations in chromatin modifications, such as histone methylation, have been suggested as mediating chemotherapy resistance in several cancer types; therefore, elucidation of the epigenetic mechanisms that underlie drug resistance may greatly contribute to the advancement of cancer therapies. In the present study, we identified histone H3-lysine 27 (H3K27) as a critical residue for epigenetic...

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Molecular mechanisms in multiple myeloma drug resistance.

Multiple myeloma (MM) is predominantly an incurable malignancy despite high-dose chemotherapy, autologous stem cell transplant and novel agents. MM is a genetically heterogeneous disease and the complexity increases as the disease progresses to a more aggressive stage. MM arises from a plasma cell, which produces and secretes non-functioning immunoglobulins. Most MM cells are sensitive to prote...

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Krüppel-like factor 4 blocks tumor cell proliferation and promotes drug resistance in multiple myeloma.

Krüppel-like factor 4 is a transcription factor with anti-proliferative effects in differentiated cells, but with the ability to reprogram adult cells into cell-cycling pluripotent cells. In cancer, Krüppel-like factor 4 acts as either an anti-oncogene or an oncogene. We analyzed Krüppel-like factor 4 gene expression in multiple myeloma using Affymetrix microarrays. We generated conditionally e...

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Smad4 inactivation promotes malignancy and drug resistance of colon cancer.

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NEK2 mediates ALDH1A1-dependent drug resistance in multiple myeloma

We reported previously that increased expression of aldehyde dehydrogenase 1 (ALDH1) in multiple myeloma (MM) is a marker of tumor-initiating cells (TICs) that is further associated with chromosomal instability (CIN). Here we demonstrate that member A1 of the ALDH1 family of proteins, ALDH1A1, is most abundantly expressed in myeloma. Enforced expression of ALDH1A1 in myeloma cells led to increa...

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ژورنال

عنوان ژورنال: Journal of Clinical Investigation

سال: 2015

ISSN: 0021-9738,1558-8238

DOI: 10.1172/jci80325