MLL translocations, histone modifications and leukaemia stem-cell development - PubMed (original) (raw)

Review

doi: 10.1038/nrc2253.

Affiliations

• PMID: 17957188
• DOI: 10.1038/nrc2253

Review

MLL translocations, histone modifications and leukaemia stem-cell development

Andrei V Krivtsov et al. Nat Rev Cancer. 2007 Nov.

Abstract

Translocations that involve the mixed lineage leukaemia (MLL) gene identify a unique group of acute leukaemias, and often predict a poor prognosis. The MLL gene encodes a DNA-binding protein that methylates histone H3 lysine 4 (H3K4), and positively regulates gene expression including multiple Hox genes. Leukaemogenic MLL translocations encode MLL fusion proteins that have lost H3K4 methyltransferase activity. A key feature of MLL fusion proteins is their ability to efficiently transform haematopoietic cells into leukaemia stem cells. The link between a chromatin modulator and leukaemia stem cells provides support for epigenetic landscapes as an important part of leukaemia and normal stem-cell development.

PubMed Disclaimer

Similar articles

• Two decades of leukemia oncoprotein epistasis: the MLL1 paradigm for epigenetic deregulation in leukemia.
  Li BE, Ernst P. Li BE, et al. Exp Hematol. 2014 Dec;42(12):995-1012. doi: 10.1016/j.exphem.2014.09.006. Epub 2014 Sep 28. Exp Hematol. 2014. PMID: 25264566 Free PMC article. Review.
• ASH1L Links Histone H3 Lysine 36 Dimethylation to MLL Leukemia.
  Zhu L, Li Q, Wong SH, Huang M, Klein BJ, Shen J, Ikenouye L, Onishi M, Schneidawind D, Buechele C, Hansen L, Duque-Afonso J, Zhu F, Martin GM, Gozani O, Majeti R, Kutateladze TG, Cleary ML. Zhu L, et al. Cancer Discov. 2016 Jul;6(7):770-83. doi: 10.1158/2159-8290.CD-16-0058. Epub 2016 May 6. Cancer Discov. 2016. PMID: 27154821 Free PMC article.
• The lncRNA LAMP5-AS1 drives leukemia cell stemness by directly modulating DOT1L methyltransferase activity in MLL leukemia.
  Wang WT, Chen TQ, Zeng ZC, Pan Q, Huang W, Han C, Fang K, Sun LY, Yang QQ, Wang D, Luo XQ, Sun YM, Chen YQ. Wang WT, et al. J Hematol Oncol. 2020 Jun 17;13(1):78. doi: 10.1186/s13045-020-00909-y. J Hematol Oncol. 2020. PMID: 32552847 Free PMC article.
• Pharmacological inhibition of LSD1 for the treatment of MLL-rearranged leukemia.
  Feng Z, Yao Y, Zhou C, Chen F, Wu F, Wei L, Liu W, Dong S, Redell M, Mo Q, Song Y. Feng Z, et al. J Hematol Oncol. 2016 Mar 12;9:24. doi: 10.1186/s13045-016-0252-7. J Hematol Oncol. 2016. PMID: 26970896 Free PMC article.
• Therapeutic strategies against hDOT1L as a potential drug target in MLL-rearranged leukemias.
  Banday S, Farooq Z, Ganai SA, Altaf M. Banday S, et al. Clin Epigenetics. 2020 May 25;12(1):73. doi: 10.1186/s13148-020-00860-2. Clin Epigenetics. 2020. PMID: 32450905 Free PMC article. Review.

Cited by

• Molecular-based classification of acute myeloid leukemia and its role in directing rational therapy: personalized medicine for profoundly promiscuous proliferations.
  Wertheim GB, Hexner E, Bagg A. Wertheim GB, et al. Mol Diagn Ther. 2012 Dec;16(6):357-69. doi: 10.1007/s40291-012-0009-0. Mol Diagn Ther. 2012. PMID: 23184342 Review.
• Oncogene interference through targeting of chromatin regulators.
  Roe JS, Vakoc CR. Roe JS, et al. Cell Cycle. 2013 May 15;12(10):1475-6. doi: 10.4161/cc.24748. Epub 2013 Apr 22. Cell Cycle. 2013. PMID: 23624838 Free PMC article. No abstract available.
• BET inhibitors in the treatment of hematologic malignancies: current insights and future prospects.
  Abedin SM, Boddy CS, Munshi HG. Abedin SM, et al. Onco Targets Ther. 2016 Sep 28;9:5943-5953. doi: 10.2147/OTT.S100515. eCollection 2016. Onco Targets Ther. 2016. PMID: 27729803 Free PMC article. Review.
• Targeting Chromatin Regulators Inhibits Leukemogenic Gene Expression in NPM1 Mutant Leukemia.
  Kühn MW, Song E, Feng Z, Sinha A, Chen CW, Deshpande AJ, Cusan M, Farnoud N, Mupo A, Grove C, Koche R, Bradner JE, de Stanchina E, Vassiliou GS, Hoshii T, Armstrong SA. Kühn MW, et al. Cancer Discov. 2016 Oct;6(10):1166-1181. doi: 10.1158/2159-8290.CD-16-0237. Epub 2016 Aug 17. Cancer Discov. 2016. PMID: 27535106 Free PMC article.
• Dependency of B-Cell Acute Lymphoblastic Leukemia and Multiple Myeloma Cell Lines on MEN1 Extends beyond MEN1-KMT2A Interaction.
  Wolffhardt TM, Ketzer F, Telese S, Wirth T, Ushmorov A. Wolffhardt TM, et al. Int J Mol Sci. 2023 Nov 17;24(22):16472. doi: 10.3390/ijms242216472. Int J Mol Sci. 2023. PMID: 38003662 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Nature Publishing Group

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information