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10.1038/nm.4416 http://scihub22266oqcxt.onion/10.1038/nm.4416 C5677536!5677536!28920958     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nat+Med 2017 ; 23 (11): 1369-76 Nephropedia Template TP {{tp|p=28920958|t=2017. The N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid differentiation of normal and leukemia cells |pdf=|usr=}}{{28920958}} gab.com Text The N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid differentiation of normal and leukemia cells JO: Nat Med http://www.kidney.de/pget.php?&tw=1&pmid=28920958 #FOAvip N6-methyladenosine (m6A) is an abundant nucleotide modification in mRNA that is required for the differentiation of mouse embryonic stem cells. However, it remains unknown whether m6A controls differentiation of normal and/or malignant myeloid hematopoietic cells. Here we show that shRNA-mediated depletion of the m6A-forming enzyme METTL3 in human hematopoietic stem/progenitor cells promotes differentiation coupled with reduced proliferation. Conversely, overexpression of wild-type METTL3, but not the catalytic-dead form of METTL3, inhibits differentiation and increases cell growth. METTL3 mRNA and protein is expressed more abundantly in acute myeloid leukemia (AML) cells compared to healthy hematopoietic stem/progenitor cells and other types of tumors. Furthermore, METTL3 depletion in humanmyeloid leukemia cell lines induces differentiation and apoptosis and delays leukemia in recipient mice in vivo. Single-nucleotide resolution mapping of m6A coupled with ribosome profiling reveals that m6A promotes the translation of c-MYC, BCL2 and PTEN mRNAs in human myeloid leukemia MOLM13 cells. Moreover, loss of METTL3 leads to increased levels of pAKT, which contributes to the differentiation effects of METTL3 depletion. Overall these results provide a rationale for therapeutic targeting of METTL3 in myeloid leukemia. Twit Text FOAVip The N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid differentiation of normal and leukemia cells ????Nat Med http://www.kidney.de/pget.php?&tw=1&pmid=28920958 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28920958 #FOAvip English Wikipedia <ref>{{Cite pmid|28920958}}</ref> The N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid differentiation of normal and leukemia cells #MMPMID28920958 Vu LP; Pickering BF; Cheng Y; Zaccara S; Nguyen D; Minuesa G; Chou T; Chow A; Saletore Y; MacKay M; Schulman J; Famulare C; Patel M; Klimek VM; Garrett-Bakelman FE; Melnick A; Carroll M; Mason CE; Jaffrey SR; Kharas MG Nat Med 2017[Nov]; 23 (11): 1369-76 PMID28920958show ga N6-methyladenosine (m6A) is an abundant nucleotide modification in mRNA that is required for the differentiation of mouse embryonic stem cells. However, it remains unknown whether m6A controls differentiation of normal and/or malignant myeloid hematopoietic cells. Here we show that shRNA-mediated depletion of the m6A-forming enzyme METTL3 in human hematopoietic stem/progenitor cells promotes differentiation coupled with reduced proliferation. Conversely, overexpression of wild-type METTL3, but not the catalytic-dead form of METTL3, inhibits differentiation and increases cell growth. METTL3 mRNA and protein is expressed more abundantly in acute myeloid leukemia (AML) cells compared to healthy hematopoietic stem/progenitor cells and other types of tumors. Furthermore, METTL3 depletion in humanmyeloid leukemia cell lines induces differentiation and apoptosis and delays leukemia in recipient mice in vivo. Single-nucleotide resolution mapping of m6A coupled with ribosome profiling reveals that m6A promotes the translation of c-MYC, BCL2 and PTEN mRNAs in human myeloid leukemia MOLM13 cells. Moreover, loss of METTL3 leads to increased levels of pAKT, which contributes to the differentiation effects of METTL3 depletion. Overall these results provide a rationale for therapeutic targeting of METTL3 in myeloid leukemia. äThe N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid di(epmc).pdf DeepDyve Pubget Overpricing