MLL-AF4 spreading identifies binding sites that are distinct from super-enhancers and that govern sensitivity to DOT1L inhibition in leukemia
J Kerry, L Godfrey, E Repapi, M Tapia, NP Blackledge… - Cell Reports, 2017 - cell.com
Understanding the underlying molecular mechanisms of defined cancers is crucial for
effective personalized therapies. Translocations of the mixed-lineage leukemia (MLL) gene …
effective personalized therapies. Translocations of the mixed-lineage leukemia (MLL) gene …
Degree of recruitment of DOT1L to MLL-AF9 defines level of H3K79 Di-and tri-methylation on target genes and transformation potential
The MLL gene is a common target of chromosomal translocations found in human leukemia.
MLL-fusion leukemia has a consistently poor outcome. One of the most common …
MLL-fusion leukemia has a consistently poor outcome. One of the most common …
Elucidating the importance of DOT1L recruitment in MLL-AF9 leukemia and hematopoiesis
SM Grigsby, A Friedman, J Chase, B Waas, J Ropa… - Cancers, 2021 - mdpi.com
Simple Summary MLL-rearranged leukemia, driven by MLL-fusion proteins, is an
aggressive, therapy-resistant leukemia found in> 60% of infant leukemia and~ 10% of adult …
aggressive, therapy-resistant leukemia found in> 60% of infant leukemia and~ 10% of adult …
MLL:: AF9 degradation induces rapid changes in transcriptional elongation and subsequent loss of an active chromatin landscape
MLL rearrangements produce fusion oncoproteins that drive leukemia development, but the
direct effects of MLL-fusion inactivation remain poorly defined. We designed models with …
direct effects of MLL-fusion inactivation remain poorly defined. We designed models with …
DOT1L, the H3K79 methyltransferase, is required for MLL-AF9–mediated leukemogenesis
Chromosomal translocations of the mixed lineage leukemia (MLL) gene are a common
cause of acute leukemias. The oncogenic function of MLL fusion proteins is, in part …
cause of acute leukemias. The oncogenic function of MLL fusion proteins is, in part …
DOT1L inhibition reveals a distinct subset of enhancers dependent on H3K79 methylation
L Godfrey, NT Crump, R Thorne, IJ Lau… - Nature …, 2019 - nature.com
Enhancer elements are a key regulatory feature of many important genes. Several general
features including the presence of specific histone modifications are used to demarcate …
features including the presence of specific histone modifications are used to demarcate …
Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia
MG Guenther, LN Lawton, T Rozovskaia… - Genes & …, 2008 - genesdev.cshlp.org
Mixed-lineage leukemia (MLL) fusion proteins are potent inducers of leukemia, but how
these proteins generate aberrant gene expression programs is poorly understood. Here we …
these proteins generate aberrant gene expression programs is poorly understood. Here we …
A higher-order configuration of the heterodimeric DOT1L–AF10 coiled-coil domains potentiates their leukemogenenic activity
X Song, L Yang, M Wang, Y Gu, B Ye… - Proceedings of the …, 2019 - National Acad Sciences
Chromosomal translocations of MLL1 (Mixed Lineage Leukemia 1) yield oncogenic chimeric
proteins containing the N-terminal portion of MLL1 fused with distinct partners. The MLL1 …
proteins containing the N-terminal portion of MLL1 fused with distinct partners. The MLL1 …
Complementary activities of DOT1L and Menin inhibitors in MLL-rearranged leukemia
C Dafflon, VJ Craig, H Mereau, J Gräsel… - Leukemia, 2017 - nature.com
Chromosomal rearrangements of the mixed lineage leukemia (MLL/KMT2A) gene leading to
oncogenic MLL-fusion proteins occur in~ 10% of acute leukemias and are associated with …
oncogenic MLL-fusion proteins occur in~ 10% of acute leukemias and are associated with …
Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l
AJ Deshpande, L Chen, M Fazio… - Blood, The Journal …, 2013 - ashpublications.org
Abstract The t (6; 11)(q27; q23) is a recurrent chromosomal rearrangement that encodes the
MLLAF6 fusion oncoprotein and is observed in patients with diverse hematologic …
MLLAF6 fusion oncoprotein and is observed in patients with diverse hematologic …