Xin Xu1,2, Björn Schneider3. 1. Laboratory for Stem Cell and Regenerative Medicine, The Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, 261053, People's Republic of China. 2. College of Bioscience and Technology, Weifang Medical University, #21406 Basic Laboratory Building, 7166 Baotongxi Street, Weifang, Shandong Province, 261053, People's Republic of China. 3. Institute of Pathology, University Medicine Rostock, Strempelstrasse 14, 18055, Rostock, Germany. bjoern.schneider@med.uni-rostock.de.
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.
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 humanAML, 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.
Authors: B D Strahl; S D Briggs; C J Brame; J A Caldwell; S S Koh; H Ma; R G Cook; J Shabanowitz; D F Hunt; M R Stallcup; C D Allis Journal: Curr Biol Date: 2001-06-26 Impact factor: 10.834
Authors: Yong Yang; Xinjing Zhang; Xiaoyan Zhang; Yishu Wang; Xintong Wang; Linda Hu; Yao Zhao; Haihua Wang; Zhanju Wang; Haiying Wang; Lin Wang; Wilhelm G Dirks; Hans G Drexler; Xin Xu; Zhenbo Hu Journal: FEBS Open Bio Date: 2020-12-16 Impact factor: 2.792