Recently MEIS1 emerged as a major determinant of the MLL-r leukemic phenotype. The latest and most efficient drugs effectively decrease the levels of MEIS1 in cancer cells. Together with an overview of the latest drugs developed to target MEIS1 in MLL-r leukemia, we review, in detail, the role of MEIS1 in embryonic and adult hematopoiesis and suggest how a more profound knowledge of MEIS1 biochemistry can be used to design potent and effective drugs against MLL-r leukemia. In addition, we present data showing that the interaction between MEIS1 and PBX1 can be blocked efficiently and might represent a new avenue in anti-MLL-r and anti-leukemic therapy.
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http://dx.doi.org/10.3390/jdb9040044 | DOI Listing |
Cancers (Basel)
November 2024
Children's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine, UNSW Medicine & Health, UNSW Centre for Childhood Cancer Research, UNSW Sydney, Sydney, NSW 2052, Australia.
Background: In infant ()-rearranged (MLL-r) acute lymphoblastic leukemia (ALL), early relapse and treatment response are currently monitored through invasive repeated bone marrow (BM) biopsies. Circulating tumor DNA (ctDNA) in peripheral blood (PB) provides a minimally invasive alternative, allowing for more frequent disease monitoring. However, a poor understanding of ctDNA dynamics has hampered its clinical translation.
View Article and Find Full Text PDFStem Cells Transl Med
November 2024
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, United States.
Zhongguo Shi Yan Xue Ye Xue Za Zhi
October 2024
Department of Hematology, The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei Province, China.
Objective: To investigate the mechanism of DNA damage and repair in -rearranged acute myeloid leukemia( -r AML)cells by the combination of Chidamide and the BRD4 inhibitor(+)-JQ-1.
Methods: -r AML cell lines Molm-13, MV4-11 and non- -r AML cell line Kasumi were divided into control group(contr), Chidamide group(chida), (+)-JQ-1 group and Combination group(combi), respectively. Cell viability of Molm-13 was measured by CCK-8 to determine optimal the concentrations of Chidamide and(+)-JQ-1.
Bioorg Chem
December 2024
School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; TMU Research Center for Drug Discovery, Taipei Medical University, Taipei, Taiwan. Electronic address:
Disruptor of telomeric silencing 1-like (DOT1L) is a key hub in histone lysine methyltransferase and an attractive therapeutic target for treating hematological malignancies including acute myeloid leukemia (AML). In this study, we report the design and synthesis of a new series of adenosine derivatives as DOT1L inhibitors by accommodating a basic linker piperidine-4-ylmethyl motif to respective aryl-urea/benzimidazole scaffolds. The anti-DOT1L enzyme activity analysis demonstrated that compounds 8, 12, and 13 strongly suppressed DOT1L activity with IC values ranging from 0.
View Article and Find Full Text PDFSci Adv
August 2024
Department of Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
The histone acylation reader eleven-nineteen leukemia (ENL) plays a pivotal role in sustaining oncogenesis in acute leukemias, particularly in -rearranged (-r) leukemia. ENL relies on its reader domain to recognize histone lysine acylation promoting oncogenic gene expression and leukemia progression. Here, we report the development of MS41, a highly potent and selective von Hippel-Lindau-recruiting ENL degrader that effectively inhibits the growth of ENL-dependent leukemia cells.
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