Sp1/NFκB/HDAC/ miR-29b Regulatory Network in KIT-Driven Myeloid Leukemia
The biologic and clinical significance of KIT overexpression that associates with KIT gain-of-function mutations occurring in subsets of acute myeloid leukemia (AML) (i.e., core binding factor AML) is unknown. Here, we show that KIT mutations lead to MYC-dependent miR-29b repression and increased le...
Gespeichert in:
| Veröffentlicht in: | Cancer cell 2010-04, Vol.17 (4), p.333-347 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 347 |
|---|---|
| container_issue | 4 |
| container_start_page | 333 |
| container_title | Cancer cell |
| container_volume | 17 |
| creator | Liu, Shujun Wu, Lai-Chu Pang, Jiuxia Santhanam, Ramasamy Schwind, Sebastian Wu, Yue-Zhong Hickey, Christopher J. Yu, Jianhua Becker, Heiko Maharry, Kati Radmacher, Michael D. Li, Chenglong Whitman, Susan P. Mishra, Anjali Stauffer, Nicole Eiring, Anna M. Briesewitz, Roger Baiocchi, Robert A. Chan, Kenneth K. Paschka, Peter Caligiuri, Michael A. Byrd, John C. Croce, Carlo M. Bloomfield, Clara D. Perrotti, Danilo Garzon, Ramiro Marcucci, Guido |
| description | The biologic and clinical significance of
KIT overexpression that associates with
KIT gain-of-function mutations occurring in subsets of acute myeloid leukemia (AML) (i.e., core binding factor AML) is unknown. Here, we show that
KIT mutations lead to
MYC-dependent
miR-29b repression and increased levels of the
miR-29b target Sp1 in KIT-driven leukemia. Sp1 enhances its own expression by participating in a NFκB/HDAC complex that further represses
miR-29b transcription. Upregulated Sp1 then binds NFκB and transactivates
KIT. Therefore, activated KIT ultimately induces its own transcription. Our results provide evidence that the mechanisms of Sp1/NFκB/HDAC/
miR-29b-dependent
KIT overexpression contribute to leukemia growth and can be successfully targeted by pharmacological disruption of the Sp1/NFκB/HDAC complex or synthetic
miR-29b treatment in KIT-driven AML.
► Aberrant KIT activity from mutation or overexpression contributes to leukemogenesis ► KIT activation inhibits
miR-29b and unblocks expression of the
miR-29b target Sp1 ► Sp1-NFκB recruits HDAC for further
miR-29b inhibition, and transactivates
KIT ► Therapeutic modulation of
miR-29b/Sp1/NFκB/HDAC network overcomes KIT-driven leukemia |
| doi_str_mv | 10.1016/j.ccr.2010.03.008 |
| format | Article |
| fullrecord | <record><control><sourceid>elsevier_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2917066</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1535610810001005</els_id><sourcerecordid>S1535610810001005</sourcerecordid><originalsourceid>FETCH-LOGICAL-c395t-a2bc7097cb9b897a07cc387b463f69b2d324f60b5d6925bde7675e2f5501fb613</originalsourceid><addsrcrecordid>eNp9kN9OwjAUhxujEUUfwLu9wEb_sHaNiQmCCBExQbxu1u4MC2Mj3cDwaj6Ez2QJxsQbr845-eX7JedD6IbgiGDCO8vIGBdR7G_MIoyTE3RBEpGEjCf81O8xi0NOcNJCl3W9xJ4hQp6jFsUs8Zm8QOPXDelMh1-f953RoNfvBGs7C6nUwQwW2yJtKrcPptB8VG4V2DJ4Gs_DgbM7KIPnPRSVzYIJbFewtukVOsvToobrn9lGb8OHeX8UTl4ex_3eJDRMxk2YUm0ElsJoqRMpUiyMYYnQXc5yLjXNGO3mHOs445LGOgPBRQw0j2NMcs0Ja6O7Y-9mq9eQGSgblxZq4-w6dXtVpVb9TUr7rhbVTlFJBObcF5BjgXFVXTvIf1mC1cGrWirvVR28KsyU9-qZ2yMD_rOdBadqY6E0kFkHplFZZf-hvwEQEn5X</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Sp1/NFκB/HDAC/ miR-29b Regulatory Network in KIT-Driven Myeloid Leukemia</title><source>Cell Press Free Archives</source><source>Elsevier ScienceDirect Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Liu, Shujun ; Wu, Lai-Chu ; Pang, Jiuxia ; Santhanam, Ramasamy ; Schwind, Sebastian ; Wu, Yue-Zhong ; Hickey, Christopher J. ; Yu, Jianhua ; Becker, Heiko ; Maharry, Kati ; Radmacher, Michael D. ; Li, Chenglong ; Whitman, Susan P. ; Mishra, Anjali ; Stauffer, Nicole ; Eiring, Anna M. ; Briesewitz, Roger ; Baiocchi, Robert A. ; Chan, Kenneth K. ; Paschka, Peter ; Caligiuri, Michael A. ; Byrd, John C. ; Croce, Carlo M. ; Bloomfield, Clara D. ; Perrotti, Danilo ; Garzon, Ramiro ; Marcucci, Guido</creator><creatorcontrib>Liu, Shujun ; Wu, Lai-Chu ; Pang, Jiuxia ; Santhanam, Ramasamy ; Schwind, Sebastian ; Wu, Yue-Zhong ; Hickey, Christopher J. ; Yu, Jianhua ; Becker, Heiko ; Maharry, Kati ; Radmacher, Michael D. ; Li, Chenglong ; Whitman, Susan P. ; Mishra, Anjali ; Stauffer, Nicole ; Eiring, Anna M. ; Briesewitz, Roger ; Baiocchi, Robert A. ; Chan, Kenneth K. ; Paschka, Peter ; Caligiuri, Michael A. ; Byrd, John C. ; Croce, Carlo M. ; Bloomfield, Clara D. ; Perrotti, Danilo ; Garzon, Ramiro ; Marcucci, Guido</creatorcontrib><description>The biologic and clinical significance of
KIT overexpression that associates with
KIT gain-of-function mutations occurring in subsets of acute myeloid leukemia (AML) (i.e., core binding factor AML) is unknown. Here, we show that
KIT mutations lead to
MYC-dependent
miR-29b repression and increased levels of the
miR-29b target Sp1 in KIT-driven leukemia. Sp1 enhances its own expression by participating in a NFκB/HDAC complex that further represses
miR-29b transcription. Upregulated Sp1 then binds NFκB and transactivates
KIT. Therefore, activated KIT ultimately induces its own transcription. Our results provide evidence that the mechanisms of Sp1/NFκB/HDAC/
miR-29b-dependent
KIT overexpression contribute to leukemia growth and can be successfully targeted by pharmacological disruption of the Sp1/NFκB/HDAC complex or synthetic
miR-29b treatment in KIT-driven AML.
► Aberrant KIT activity from mutation or overexpression contributes to leukemogenesis ► KIT activation inhibits
miR-29b and unblocks expression of the
miR-29b target Sp1 ► Sp1-NFκB recruits HDAC for further
miR-29b inhibition, and transactivates
KIT ► Therapeutic modulation of
miR-29b/Sp1/NFκB/HDAC network overcomes KIT-driven leukemia</description><identifier>ISSN: 1535-6108</identifier><identifier>EISSN: 1878-3686</identifier><identifier>DOI: 10.1016/j.ccr.2010.03.008</identifier><identifier>PMID: 20385359</identifier><language>eng</language><publisher>Elsevier Inc</publisher><subject>CELLCYCLE ; DNA ; RNA</subject><ispartof>Cancer cell, 2010-04, Vol.17 (4), p.333-347</ispartof><rights>2010 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c395t-a2bc7097cb9b897a07cc387b463f69b2d324f60b5d6925bde7675e2f5501fb613</citedby><cites>FETCH-LOGICAL-c395t-a2bc7097cb9b897a07cc387b463f69b2d324f60b5d6925bde7675e2f5501fb613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1535610810001005$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids></links><search><creatorcontrib>Liu, Shujun</creatorcontrib><creatorcontrib>Wu, Lai-Chu</creatorcontrib><creatorcontrib>Pang, Jiuxia</creatorcontrib><creatorcontrib>Santhanam, Ramasamy</creatorcontrib><creatorcontrib>Schwind, Sebastian</creatorcontrib><creatorcontrib>Wu, Yue-Zhong</creatorcontrib><creatorcontrib>Hickey, Christopher J.</creatorcontrib><creatorcontrib>Yu, Jianhua</creatorcontrib><creatorcontrib>Becker, Heiko</creatorcontrib><creatorcontrib>Maharry, Kati</creatorcontrib><creatorcontrib>Radmacher, Michael D.</creatorcontrib><creatorcontrib>Li, Chenglong</creatorcontrib><creatorcontrib>Whitman, Susan P.</creatorcontrib><creatorcontrib>Mishra, Anjali</creatorcontrib><creatorcontrib>Stauffer, Nicole</creatorcontrib><creatorcontrib>Eiring, Anna M.</creatorcontrib><creatorcontrib>Briesewitz, Roger</creatorcontrib><creatorcontrib>Baiocchi, Robert A.</creatorcontrib><creatorcontrib>Chan, Kenneth K.</creatorcontrib><creatorcontrib>Paschka, Peter</creatorcontrib><creatorcontrib>Caligiuri, Michael A.</creatorcontrib><creatorcontrib>Byrd, John C.</creatorcontrib><creatorcontrib>Croce, Carlo M.</creatorcontrib><creatorcontrib>Bloomfield, Clara D.</creatorcontrib><creatorcontrib>Perrotti, Danilo</creatorcontrib><creatorcontrib>Garzon, Ramiro</creatorcontrib><creatorcontrib>Marcucci, Guido</creatorcontrib><title>Sp1/NFκB/HDAC/ miR-29b Regulatory Network in KIT-Driven Myeloid Leukemia</title><title>Cancer cell</title><description>The biologic and clinical significance of
KIT overexpression that associates with
KIT gain-of-function mutations occurring in subsets of acute myeloid leukemia (AML) (i.e., core binding factor AML) is unknown. Here, we show that
KIT mutations lead to
MYC-dependent
miR-29b repression and increased levels of the
miR-29b target Sp1 in KIT-driven leukemia. Sp1 enhances its own expression by participating in a NFκB/HDAC complex that further represses
miR-29b transcription. Upregulated Sp1 then binds NFκB and transactivates
KIT. Therefore, activated KIT ultimately induces its own transcription. Our results provide evidence that the mechanisms of Sp1/NFκB/HDAC/
miR-29b-dependent
KIT overexpression contribute to leukemia growth and can be successfully targeted by pharmacological disruption of the Sp1/NFκB/HDAC complex or synthetic
miR-29b treatment in KIT-driven AML.
► Aberrant KIT activity from mutation or overexpression contributes to leukemogenesis ► KIT activation inhibits
miR-29b and unblocks expression of the
miR-29b target Sp1 ► Sp1-NFκB recruits HDAC for further
miR-29b inhibition, and transactivates
KIT ► Therapeutic modulation of
miR-29b/Sp1/NFκB/HDAC network overcomes KIT-driven leukemia</description><subject>CELLCYCLE</subject><subject>DNA</subject><subject>RNA</subject><issn>1535-6108</issn><issn>1878-3686</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNp9kN9OwjAUhxujEUUfwLu9wEb_sHaNiQmCCBExQbxu1u4MC2Mj3cDwaj6Ez2QJxsQbr845-eX7JedD6IbgiGDCO8vIGBdR7G_MIoyTE3RBEpGEjCf81O8xi0NOcNJCl3W9xJ4hQp6jFsUs8Zm8QOPXDelMh1-f953RoNfvBGs7C6nUwQwW2yJtKrcPptB8VG4V2DJ4Gs_DgbM7KIPnPRSVzYIJbFewtukVOsvToobrn9lGb8OHeX8UTl4ex_3eJDRMxk2YUm0ElsJoqRMpUiyMYYnQXc5yLjXNGO3mHOs445LGOgPBRQw0j2NMcs0Ja6O7Y-9mq9eQGSgblxZq4-w6dXtVpVb9TUr7rhbVTlFJBObcF5BjgXFVXTvIf1mC1cGrWirvVR28KsyU9-qZ2yMD_rOdBadqY6E0kFkHplFZZf-hvwEQEn5X</recordid><startdate>20100413</startdate><enddate>20100413</enddate><creator>Liu, Shujun</creator><creator>Wu, Lai-Chu</creator><creator>Pang, Jiuxia</creator><creator>Santhanam, Ramasamy</creator><creator>Schwind, Sebastian</creator><creator>Wu, Yue-Zhong</creator><creator>Hickey, Christopher J.</creator><creator>Yu, Jianhua</creator><creator>Becker, Heiko</creator><creator>Maharry, Kati</creator><creator>Radmacher, Michael D.</creator><creator>Li, Chenglong</creator><creator>Whitman, Susan P.</creator><creator>Mishra, Anjali</creator><creator>Stauffer, Nicole</creator><creator>Eiring, Anna M.</creator><creator>Briesewitz, Roger</creator><creator>Baiocchi, Robert A.</creator><creator>Chan, Kenneth K.</creator><creator>Paschka, Peter</creator><creator>Caligiuri, Michael A.</creator><creator>Byrd, John C.</creator><creator>Croce, Carlo M.</creator><creator>Bloomfield, Clara D.</creator><creator>Perrotti, Danilo</creator><creator>Garzon, Ramiro</creator><creator>Marcucci, Guido</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20100413</creationdate><title>Sp1/NFκB/HDAC/ miR-29b Regulatory Network in KIT-Driven Myeloid Leukemia</title><author>Liu, Shujun ; Wu, Lai-Chu ; Pang, Jiuxia ; Santhanam, Ramasamy ; Schwind, Sebastian ; Wu, Yue-Zhong ; Hickey, Christopher J. ; Yu, Jianhua ; Becker, Heiko ; Maharry, Kati ; Radmacher, Michael D. ; Li, Chenglong ; Whitman, Susan P. ; Mishra, Anjali ; Stauffer, Nicole ; Eiring, Anna M. ; Briesewitz, Roger ; Baiocchi, Robert A. ; Chan, Kenneth K. ; Paschka, Peter ; Caligiuri, Michael A. ; Byrd, John C. ; Croce, Carlo M. ; Bloomfield, Clara D. ; Perrotti, Danilo ; Garzon, Ramiro ; Marcucci, Guido</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c395t-a2bc7097cb9b897a07cc387b463f69b2d324f60b5d6925bde7675e2f5501fb613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>CELLCYCLE</topic><topic>DNA</topic><topic>RNA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Shujun</creatorcontrib><creatorcontrib>Wu, Lai-Chu</creatorcontrib><creatorcontrib>Pang, Jiuxia</creatorcontrib><creatorcontrib>Santhanam, Ramasamy</creatorcontrib><creatorcontrib>Schwind, Sebastian</creatorcontrib><creatorcontrib>Wu, Yue-Zhong</creatorcontrib><creatorcontrib>Hickey, Christopher J.</creatorcontrib><creatorcontrib>Yu, Jianhua</creatorcontrib><creatorcontrib>Becker, Heiko</creatorcontrib><creatorcontrib>Maharry, Kati</creatorcontrib><creatorcontrib>Radmacher, Michael D.</creatorcontrib><creatorcontrib>Li, Chenglong</creatorcontrib><creatorcontrib>Whitman, Susan P.</creatorcontrib><creatorcontrib>Mishra, Anjali</creatorcontrib><creatorcontrib>Stauffer, Nicole</creatorcontrib><creatorcontrib>Eiring, Anna M.</creatorcontrib><creatorcontrib>Briesewitz, Roger</creatorcontrib><creatorcontrib>Baiocchi, Robert A.</creatorcontrib><creatorcontrib>Chan, Kenneth K.</creatorcontrib><creatorcontrib>Paschka, Peter</creatorcontrib><creatorcontrib>Caligiuri, Michael A.</creatorcontrib><creatorcontrib>Byrd, John C.</creatorcontrib><creatorcontrib>Croce, Carlo M.</creatorcontrib><creatorcontrib>Bloomfield, Clara D.</creatorcontrib><creatorcontrib>Perrotti, Danilo</creatorcontrib><creatorcontrib>Garzon, Ramiro</creatorcontrib><creatorcontrib>Marcucci, Guido</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Shujun</au><au>Wu, Lai-Chu</au><au>Pang, Jiuxia</au><au>Santhanam, Ramasamy</au><au>Schwind, Sebastian</au><au>Wu, Yue-Zhong</au><au>Hickey, Christopher J.</au><au>Yu, Jianhua</au><au>Becker, Heiko</au><au>Maharry, Kati</au><au>Radmacher, Michael D.</au><au>Li, Chenglong</au><au>Whitman, Susan P.</au><au>Mishra, Anjali</au><au>Stauffer, Nicole</au><au>Eiring, Anna M.</au><au>Briesewitz, Roger</au><au>Baiocchi, Robert A.</au><au>Chan, Kenneth K.</au><au>Paschka, Peter</au><au>Caligiuri, Michael A.</au><au>Byrd, John C.</au><au>Croce, Carlo M.</au><au>Bloomfield, Clara D.</au><au>Perrotti, Danilo</au><au>Garzon, Ramiro</au><au>Marcucci, Guido</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sp1/NFκB/HDAC/ miR-29b Regulatory Network in KIT-Driven Myeloid Leukemia</atitle><jtitle>Cancer cell</jtitle><date>2010-04-13</date><risdate>2010</risdate><volume>17</volume><issue>4</issue><spage>333</spage><epage>347</epage><pages>333-347</pages><issn>1535-6108</issn><eissn>1878-3686</eissn><abstract>The biologic and clinical significance of
KIT overexpression that associates with
KIT gain-of-function mutations occurring in subsets of acute myeloid leukemia (AML) (i.e., core binding factor AML) is unknown. Here, we show that
KIT mutations lead to
MYC-dependent
miR-29b repression and increased levels of the
miR-29b target Sp1 in KIT-driven leukemia. Sp1 enhances its own expression by participating in a NFκB/HDAC complex that further represses
miR-29b transcription. Upregulated Sp1 then binds NFκB and transactivates
KIT. Therefore, activated KIT ultimately induces its own transcription. Our results provide evidence that the mechanisms of Sp1/NFκB/HDAC/
miR-29b-dependent
KIT overexpression contribute to leukemia growth and can be successfully targeted by pharmacological disruption of the Sp1/NFκB/HDAC complex or synthetic
miR-29b treatment in KIT-driven AML.
► Aberrant KIT activity from mutation or overexpression contributes to leukemogenesis ► KIT activation inhibits
miR-29b and unblocks expression of the
miR-29b target Sp1 ► Sp1-NFκB recruits HDAC for further
miR-29b inhibition, and transactivates
KIT ► Therapeutic modulation of
miR-29b/Sp1/NFκB/HDAC network overcomes KIT-driven leukemia</abstract><pub>Elsevier Inc</pub><pmid>20385359</pmid><doi>10.1016/j.ccr.2010.03.008</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1535-6108 |
| ispartof | Cancer cell, 2010-04, Vol.17 (4), p.333-347 |
| issn | 1535-6108 1878-3686 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2917066 |
| source | Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | CELLCYCLE DNA RNA |
| title | Sp1/NFκB/HDAC/ miR-29b Regulatory Network in KIT-Driven Myeloid Leukemia |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T05%3A26%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-elsevier_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Sp1/NF%CE%BAB/HDAC/%20miR-29b%20Regulatory%20Network%20in%20KIT-Driven%20Myeloid%20Leukemia&rft.jtitle=Cancer%20cell&rft.au=Liu,%20Shujun&rft.date=2010-04-13&rft.volume=17&rft.issue=4&rft.spage=333&rft.epage=347&rft.pages=333-347&rft.issn=1535-6108&rft.eissn=1878-3686&rft_id=info:doi/10.1016/j.ccr.2010.03.008&rft_dat=%3Celsevier_pubme%3ES1535610810001005%3C/elsevier_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/20385359&rft_els_id=S1535610810001005&rfr_iscdi=true |