2014
DOI: 10.1038/nature13605
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Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia

Abstract: T cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy with dismal overall prognosis, exhibiting up to a 25% relapse rate, mainly due to the absence of non-cytotoxic targeted therapy options. Despite the fact that drugs targeting the function of key epigenetic factors have been approved in the context of hematopoietic disorders1 and the recent identification of mutations affecting chromatin modulators in a variety of leukemias2,3, “epigenetic” drugs are not currently used for TALL treatment.… Show more

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Cited by 333 publications
(415 citation statements)
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References 50 publications
(91 reference statements)
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“…4). This appears to be of importance in human T-acute lymphocyte leukemia (ALL), a childhood tumor more common in males than in females and a corresponding experimental model of the disease [112][113][114] . Additional X-linked players altered in T-ALL are the PHF6 and RPL10 genes, which are mutated almost exclusively in male patients 115,116 .…”
Section: A) X Chromosomementioning
confidence: 99%
“…4). This appears to be of importance in human T-acute lymphocyte leukemia (ALL), a childhood tumor more common in males than in females and a corresponding experimental model of the disease [112][113][114] . Additional X-linked players altered in T-ALL are the PHF6 and RPL10 genes, which are mutated almost exclusively in male patients 115,116 .…”
Section: A) X Chromosomementioning
confidence: 99%
“…81,113,114 Indeed, treatment of T-ALL cells with GSK-J4 also resulted in reduced cell proliferation and increased K27M methylation. 82 In this study, the antitumor activities of the GSK-J4 inhibitor was also specific for T-ALL cells, and the main action of this inhibitor in T-ALL is also thought to be channeled through the inhibition of JMJD3 activity. 82 …”
Section: H3k9mtsmentioning
confidence: 99%
“…Somatic loss-of-function mutations of UTX are found in multiple myeloma, esophageal squamous cell carcinomas, renal carcinomas, and occasionally in breast cancer, AML, T-ALL, GBM, and colorectal and bladder cancer (Table 1) (for review see. 70,81,82 ), suggestive of a tumor suppressor role for UTX. Both JMJD3 and UTX function as part of a transcriptional activator complex that includes the MLL3/MLL4 H3K4 methyltransferases, indicating that these enzymes have a dual role involving removal of H3K27 methyl marks and addition of methyl groups to H3K4 (reviewed in 76 ).…”
Section: H3k9mtsmentioning
confidence: 99%
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