Home > Publications database > Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6. > print

001     130701
005     20240228143455.0
024 7 _ |a 10.1182/blood-2015-11-683581
|2 doi
024 7 _ |a pmid:27099147
|2 pmid
024 7 _ |a pmc:PMC4920675
|2 pmc
024 7 _ |a 0006-4971
|2 ISSN
024 7 _ |a 1528-0020
|2 ISSN
024 7 _ |a altmetric:6897886
|2 altmetric
037 _ _ |a DKFZ-2017-05779
041 _ _ |a eng
082 _ _ |a 610
100 1 _ |a Uras, Iris Z
|b 0
245 _ _ |a Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6.
260 _ _ |a Stanford, Calif.
|c 2016
|b HighWire Press
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1524563461_19306
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a Up to 30% of patients with acute myeloid leukemia have constitutively activating internal tandem duplications (ITDs) of the FLT3 receptor tyrosine kinase. Such mutations are associated with a poor prognosis and a high propensity to relapse after remission. FLT3 inhibitors are being developed as targeted therapy for FLT3-ITD(+) acute myeloid leukemia; however, their use is complicated by rapid development of resistance, which illustrates the need for additional therapeutic targets. We show that the US Food and Drug Administration-approved CDK4/6 kinase inhibitor palbociclib induces apoptosis of FLT3-ITD leukemic cells. The effect is specific for FLT3-mutant cells and is ascribed to the transcriptional activity of CDK6: CDK6 but not its functional homolog CDK4 is found at the promoters of the FLT3 and PIM1 genes, another important leukemogenic driver. There CDK6 regulates transcription in a kinase-dependent manner. Of potential clinical relevance, combined treatment with palbociclib and FLT3 inhibitors results in synergistic cytotoxicity. Simultaneously targeting two critical signaling nodes in leukemogenesis could represent a therapeutic breakthrough, leading to complete remission and overcoming resistance to FLT3 inhibitors.
536 _ _ |a 317 - Translational cancer research (POF3-317)
|0 G:(DE-HGF)POF3-317
|c POF3-317
|f POF III
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a Mutant Proteins
|2 NLM Chemicals
650 _ 7 |a Piperazines
|2 NLM Chemicals
650 _ 7 |a Protein Kinase Inhibitors
|2 NLM Chemicals
650 _ 7 |a Proto-Oncogene Proteins
|2 NLM Chemicals
650 _ 7 |a Pyridines
|2 NLM Chemicals
650 _ 7 |a FLT3 protein, human
|0 EC 2.7.10.1
|2 NLM Chemicals
650 _ 7 |a fms-Like Tyrosine Kinase 3
|0 EC 2.7.10.1
|2 NLM Chemicals
650 _ 7 |a PIM3 protein, human
|0 EC 2.7.11.1
|2 NLM Chemicals
650 _ 7 |a Protein-Serine-Threonine Kinases
|0 EC 2.7.11.1
|2 NLM Chemicals
650 _ 7 |a CDK6 protein, human
|0 EC 2.7.11.22
|2 NLM Chemicals
650 _ 7 |a Cyclin-Dependent Kinase 6
|0 EC 2.7.11.22
|2 NLM Chemicals
650 _ 7 |a palbociclib
|0 G9ZF61LE7G
|2 NLM Chemicals
700 1 _ |a Walter, Gina
|0 P:(DE-He78)8d1407b71d2891f2a088c1c5b20062e8
|b 1
|e First author
|u dkfz
700 1 _ |a Scheicher, Ruth
|b 2
700 1 _ |a Bellutti, Florian
|b 3
700 1 _ |a Prchal-Murphy, Michaela
|b 4
700 1 _ |a Tigan, Anca S
|b 5
700 1 _ |a Valent, Peter
|b 6
700 1 _ |a Heidel, Florian H
|b 7
700 1 _ |a Kubicek, Stefan
|b 8
700 1 _ |a Scholl, Claudia
|0 P:(DE-He78)2c1a21d1cf5fdc9e297512c9d1354250
|b 9
|u dkfz
700 1 _ |a Fröhling, Stefan
|0 P:(DE-He78)f0144d171d26dbedb67c9db1df35629d
|b 10
|u dkfz
700 1 _ |a Sexl, Veronika
|b 11
773 _ _ |a 10.1182/blood-2015-11-683581
|g Vol. 127, no. 23, p. 2890 - 2902
|0 PERI:(DE-600)1468538-3
|n 23
|p 2890 - 2902
|t Blood
|v 127
|y 2016
|x 1528-0020
909 C O |o oai:inrepo02.dkfz.de:130701
|p VDB
910 1 _ |a Deutsches Krebsforschungszentrum
|0 I:(DE-588b)2036810-0
|k DKFZ
|b 1
|6 P:(DE-He78)8d1407b71d2891f2a088c1c5b20062e8
910 1 _ |a Deutsches Krebsforschungszentrum
|0 I:(DE-588b)2036810-0
|k DKFZ
|b 9
|6 P:(DE-He78)2c1a21d1cf5fdc9e297512c9d1354250
910 1 _ |a Deutsches Krebsforschungszentrum
|0 I:(DE-588b)2036810-0
|k DKFZ
|b 10
|6 P:(DE-He78)f0144d171d26dbedb67c9db1df35629d
913 1 _ |a DE-HGF
|l Krebsforschung
|1 G:(DE-HGF)POF3-310
|0 G:(DE-HGF)POF3-317
|2 G:(DE-HGF)POF3-300
|v Translational cancer research
|x 0
|4 G:(DE-HGF)POF
|3 G:(DE-HGF)POF3
|b Gesundheit
914 1 _ |y 2016
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b BLOOD : 2015
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0310
|2 StatID
|b NCBI Molecular Biology Database
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0600
|2 StatID
|b Ebsco Academic Search
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b ASC
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Thomson Reuters Master Journal List
915 _ _ |a WoS
|0 StatID:(DE-HGF)0110
|2 StatID
|b Science Citation Index
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
915 _ _ |a WoS
|0 StatID:(DE-HGF)0111
|2 StatID
|b Science Citation Index Expanded
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1110
|2 StatID
|b Current Contents - Clinical Medicine
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1030
|2 StatID
|b Current Contents - Life Sciences
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
915 _ _ |a IF >= 10
|0 StatID:(DE-HGF)9910
|2 StatID
|b BLOOD : 2015
920 1 _ |0 I:(DE-He78)G100-20160331
|k G100
|l Translationale Onkologie
|x 0
920 1 _ |0 I:(DE-He78)G102-20160331
|k G102
|l Angewandte Funktionelle Genomik
|x 1
920 1 _ |0 I:(DE-He78)L101-20160331
|k L101
|l DKTK Heidelberg
|x 2
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a I:(DE-He78)G100-20160331
980 _ _ |a I:(DE-He78)G102-20160331
980 _ _ |a I:(DE-He78)L101-20160331
980 _ _ |a UNRESTRICTED

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21