2020
DOI: 10.1038/s41388-020-01408-7
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Restoring MLL reactivates latent tumor suppression-mediated vulnerability to proteasome inhibitors

Abstract: MLL undergoes multiple distinct chromosomal translocations to yield aggressive leukemia with dismal outcomes. Besides their well-established role in leukemogenesis, MLL fusions also possess latent tumor-suppressive activity, which can be exploited as effective cancer treatment strategies using pharmacological means such as proteasome inhibitors (PIs). Here, using MLL-rearranged xenografts and MLL leukemic cells as models, we show that wild-type MLL is indispensable for the latent tumor-suppressive activity of … Show more

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Cited by 7 publications
(19 citation statements)
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“…3d, e). In addition, consistent with a critical role in the drugresistance and DNA-damage responses, 19,22,44 reduction of MLL in PI-tolerant cells was associated with an increase in histone γ-H2AX (Fig. 3e).…”
Section: Mll Directly Regulates the Transcriptional Activity Of Cyclisupporting
confidence: 72%
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“…3d, e). In addition, consistent with a critical role in the drugresistance and DNA-damage responses, 19,22,44 reduction of MLL in PI-tolerant cells was associated with an increase in histone γ-H2AX (Fig. 3e).…”
Section: Mll Directly Regulates the Transcriptional Activity Of Cyclisupporting
confidence: 72%
“…18 However, the inevitable emergence of PI resistance limits the clinical application of bortezomib. 19,20 There is thus a need to identify the mechanism underlying PI resistance and to design novel combination strategies to overcome resistance and promote the application of PIs for MLL leukemias.…”
Section: Introductionmentioning
confidence: 99%
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“…Transplantation of in vitro-manipulated cells is a widely used and powerful procedure in basic research and translational studies in the field of hematology. For example, cell line-derived xenograft mouse models are essential in studying the pathogenesis of diseases, testing the efficacy of treatment, and investigating molecular mechanisms of therapeutic resistance [1][2][3]. Ex vivo human hematopoietic stem cell (HSC) expansion and generating HSCs through in vitro reprogramming constitute a new hope for solving the issue of HSC shortage [4,5].…”
mentioning
confidence: 99%