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Cellular Oncology

, Volume 42, Issue 2, pp 117–130 | Cite as

Therapeutic targeting potential of chromatin-associated proteins in MLL-rearranged acute leukemia

  • Xin Xu
  • Björn SchneiderEmail author
Review
  • 136 Downloads

Abstract

Background

Acute leukemias (AL) with a Mixed Lineage Leukemia (MLL) gene rearrangement (MLLr) represent a group of leukemic entities conferring intermediate to adverse prognoses. Multiple chromatin-associated proteins have been shown to play essential roles during the genesis of MLLr AL. Some chromatin-associated proteins function as negative regulators of MLLr AL whereas others are required for leukemic initiation or maintenance - the latter group constituting potential therapeutic targets. Most of the identified proteins have been functionally analyzed using experimental models with human/murine normal cells transformed by MLL-AF9 or other MLL fusion products, which may recapitulate most but not all aspects of human AML, such as immune system interactions – features of which the importance is rapidly emerging.

Conclusions

Here, we review chromatin-associated proteins fundamental to MLLr AL development, highlighting those with targeting potential by small molecule inhibitors. In particular, we focus on synthetic targeting of multiple chromatin-associated proteins, a strategy that shows superior therapeutic efficacy and offers hope for overcoming drug resistance.

Keywords

Acute leukemia MLL Chromatin associated proteins Small molecule inhibitors Synthetic targeting 

Notes

Funding

Xin Xu was funded by the National Natural Science Foundation of China (NSFC; grant # 81370628 and # 81570157), the Scientific Research Foundation for Returned Overseas Chinese Scholars, State Education Ministry, Shandong Provincial Natural Science Foundation, China (grant # ZR2015CL023), and the Shandong Province Higher Educational Science and Technology Program (J16LL54).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© International Society for Cellular Oncology 2018

Authors and Affiliations

  1. 1.Laboratory for Stem Cell and Regenerative MedicineThe Affiliated Hospital of Weifang Medical UniversityWeifangPeople’s Republic of China
  2. 2.College of Bioscience and TechnologyWeifang Medical UniversityWeifangPeople’s Republic of China
  3. 3.Institute of PathologyUniversity Medicine RostockRostockGermany

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