A Box of Chemistry to Inhibit the MEN1 Tumor Suppressor Gene Promoting Leukemia
Sign Up to like & getrecommendations! Published in 2021 at "Chemmedchem"
DOI: 10.1002/cmdc.202000972
Abstract: Targeting protein‐protein interactions (PPIs) with small‐molecule inhibitors has become a hotbed of modern drug development. In this review, we describe a new class of PPI inhibitors that block menin from binding to MLL proteins. Menin… read more here.
Keywords: tumor suppressor; leukemia; mll; chemistry ... See more keywords
A Menin-MLL Inhibitor Induces Specific Chromatin Changes and Eradicates Disease in Models of MLL-Rearranged Leukemia.
Sign Up to like & getrecommendations! Published in 2019 at "Cancer cell"
DOI: 10.1016/j.ccell.2019.11.001
Abstract: Inhibition of the Menin (MEN1) and MLL (MLL1, KMT2A) interaction is a potential therapeutic strategy for MLL-rearranged (MLL-r) leukemia. Structure-based design yielded the potent, highly selective, and orally bioavailable small-molecule inhibitor VTP50469. Cell lines carrying… read more here.
Keywords: mll; mll rearranged; menin mll; mll inhibitor ... See more keywords
MLL/WDR5 Complex Regulates Kif2A Localization to Ensure Chromosome Congression and Proper Spindle Assembly during Mitosis.
Sign Up to like & getrecommendations! Published in 2017 at "Developmental cell"
DOI: 10.1016/j.devcel.2017.05.023
Abstract: Mixed-lineage leukemia (MLL), along with multisubunit (WDR5, RbBP5, ASH2L, and DPY30) complex catalyzes the trimethylation of H3K4, leading to gene activation. Here, we characterize a chromatin-independent role for MLL during mitosis. MLL and WDR5 localize… read more here.
Keywords: mitosis; mll complex; mll; localization ... See more keywords
Identification of novel biomarkers for MLL-translocated acute myeloid leukemia.
Sign Up to like & getrecommendations! Published in 2017 at "Experimental hematology"
DOI: 10.1016/j.exphem.2017.08.006
Abstract: Acute myeloid leukemias (AMLs) with translocations of the mixed lineage leukemia (MLL/KMT2A) gene are common in young patients and are generally associated with poor clinical outcomes. The molecular biology of MLL fusion genes remains incompletely… read more here.
Keywords: mll; leukemia; identification novel; acute myeloid ... See more keywords
Massive Localized Lymphedema: A Case-Control Study.
Sign Up to like & getrecommendations! Published in 2017 at "Journal of the American College of Surgeons"
DOI: 10.1016/j.jamcollsurg.2016.10.047
Abstract: BACKGROUND Massive localized lymphedema (MLL) is an area of skin and subcutaneous overgrowth associated with obesity. The purpose of this study was to determine whether MLL results from obesity-induced lymphedema (OIL) and to characterize the… read more here.
Keywords: localized lymphedema; massive localized; bmi; study ... See more keywords
Absence of the Shb gene in mixed-lineage leukemia MLL-AF9 cells increases latency in mice despite higher proliferation rates in vitro.
Sign Up to like & getrecommendations! Published in 2020 at "Experimental cell research"
DOI: 10.1016/j.yexcr.2020.112368
Abstract: Mixed lineage leukemia (MLL) arises from several KMT2A-gene chromosomal translocations. Shb gene deficiency has been found to exhibit pleiotropic effects in different models of leukemia, and consequently, this study aimed to investigate MLL-AF9-induced leukemia in… read more here.
Keywords: af9 cells; mll af9; leukemia; gene ... See more keywords
Discovery of M-1121 as an Orally Active Covalent Inhibitor of Menin-MLL Interaction Capable of Achieving Complete and Long-Lasting Tumor Regression.
Sign Up to like & getrecommendations! Published in 2021 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c00789
Abstract: Targeting the menin-MLL protein-protein interaction is being pursued as a new therapeutic strategy for the treatment of acute leukemia carrying MLL-rearrangements (MLLr leukemia). Herein, we report M-1121, a covalent and orally active inhibitor of the… read more here.
Keywords: orally active; menin; covalent; interaction ... See more keywords
Computer-Aided Discovery of Massonianoside B as a Novel Selective DOT1L Inhibitor.
Sign Up to like & getrecommendations! Published in 2019 at "ACS chemical biology"
DOI: 10.1021/acschembio.8b00933
Abstract: Protein methyltransferases (PMTs) are involved in numerous biological processes and have been studied as a promising target class in the field of oncology and other diseases. Disruptor of telomeric silencing 1-like (DOT1L), a histone H3… read more here.
Keywords: massonianoside; dot1l inhibitor; discovery; mll ... See more keywords
Human MLL/KMT2A gene exhibits a second breakpoint cluster region for recurrent MLL–USP2 fusions
Sign Up to like & getrecommendations! Published in 2019 at "Leukemia"
DOI: 10.1038/s41375-019-0451-7
Abstract: For nearly 3 decades, the human MLL (KMT2A) gene and its rearrangements have been investigated in many different laboratories around the world. At our diagnostic center (DCAL Frankfurt), our standard strategy for the identification of… read more here.
Keywords: bcr; breakpoint; mll usp2; gene ... See more keywords
Restoration of microRNA function impairs MYC-dependent maintenance of MLL leukemia
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DOI: 10.1038/s41375-020-0768-2
Abstract: MicroRNAs (miRNAs) are a class of small noncoding RNAs that have critical functions in gene silencing by binding to complementary mRNAs to induce their degradation or translational repression [1]. Interestingly, only a small fraction of… read more here.
Keywords: leukemic cells; mll leukemic; function; mll ... See more keywords
Tip60 activates Hoxa9 and Meis1 expression through acetylation of H2A.Z, promoting MLL-AF10 and MLL-ENL acute myeloid leukemia
Sign Up to like & getrecommendations! Published in 2021 at "Leukemia"
DOI: 10.1038/s41375-021-01244-y
Abstract: Chromosome translocations involving the MLL gene are common rearrangements in leukemia. Such translocations fuse the MLL 5’-region to partner genes in frame, producing MLL-fusions that cause MLL-related leukemia. MLL-fusions activate transcription of target genes such… read more here.
Keywords: mll enl; af10 mll; leukemia; mll ... See more keywords