WEB-2086 and WEB-2170 trigger apoptosis in both ATRA-sensitive and -resistant promyelocytic leukemia cells and greatly enhance ATRA differentiation potential

AbstractExtracellular vesicles (EVs) are membrane-derived heterogeneous vesicles that mediate intercellular communications. They have recently been considered as ideal vehicles for drug-delivery systems, and immune cells are suggested as a potential source for drug-loaded EVs. In this study, we investigated the possibility of neutrophils as a source for drug-loaded EVs. Neutrophil-like differentiated human promyelocytic leukemia cells (dHL-60) produced massive amounts of EVs within 1 h. The dHL-60 cells are also easily loaded with various cargoes such as antibiotics (penicillin), anticancer drug (paclitaxel), chemoattractant (MCP-1), miRNA, and Cas9. The EVs derived from the dHL-60 cells showed efficient incorporation of these cargoes and significant effector functions, such as bactericidal activity, monocyte chemotaxis, and macrophage polarization. Our results suggest that neutrophils or neutrophil-like promyelocytic cells could be an attractive source for drug-delivery EVs.

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Effects of co-administration of arsenic trioxide and Schiff base oxovanadium complex on the induction of apoptosis in acute promyelocytic leukemia cells

BioMetals ◽

10.1007/s10534-021-00330-z ◽

2021 ◽

Author(s):

Sara Mirjalili ◽

Ali Khaleghian ◽

Fatemeh Kalalinia

Keyword(s):

Schiff Base ◽

Arsenic Trioxide ◽

Acute Promyelocytic Leukemia ◽

Promyelocytic Leukemia ◽

Leukemia Cells ◽

Oxovanadium Complex ◽

Induction Of Apoptosis

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Discrepancy between in-vitro and in-vivo inductions of differentiation by retinoids of human acute promyelocytic leukemia cells in relapse

Leukemia Research ◽

10.1016/0145-2126(85)90039-6 ◽

1985 ◽

Vol 9 (12) ◽

pp. 1475-1478 ◽

Cited By ~ 10

Author(s):

Kazumi Sampi ◽

Yoshio Honma ◽

Motoo Hozumi ◽

Masaharu Sakurai

Keyword(s):

Acute Promyelocytic Leukemia ◽

Promyelocytic Leukemia ◽

Leukemia Cells ◽

Human Acute Promyelocytic Leukemia

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Erratum: Arsenic trioxide (ATO) and MEK1 inhibition synergize to induce apoptosis in acute promyelocytic leukemia cells

Leukemia ◽

10.1038/sj.leu.2403642 ◽

2005 ◽

Vol 19 (2) ◽

pp. 322-322

Author(s):

P Lunghi ◽

A Tabilio ◽

F Lo-Coco ◽

P Pelicci ◽

A Bonati

Keyword(s):

Arsenic Trioxide ◽

Acute Promyelocytic Leukemia ◽

Promyelocytic Leukemia ◽

Leukemia Cells

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Maintenance of Open Chromatin and Selective Genomic Occupancy at the Cell Cycle-Regulated Histone H4 Promoter during Differentiation of HL-60 Promyelocytic Leukemia Cells

Molecular and Cellular Biology ◽

10.1128/mcb.23.4.1460-1469.2003 ◽

2003 ◽

Vol 23 (4) ◽

pp. 1460-1469 ◽

Cited By ~ 19

Author(s):

Hayk Hovhannisyan ◽

Brian Cho ◽

Partha Mitra ◽

Martin Montecino ◽

Gary S. Stein ◽

...

Keyword(s):

Cell Cycle ◽

Kinase Inhibitor ◽

Restriction Enzymes ◽

Dnase I ◽

Promyelocytic Leukemia ◽

Micrococcal Nuclease ◽

Leukemia Cells ◽

N Gene ◽

Open Chromatin ◽

Histone H4

ABSTRACT During the shutdown of proliferation and onset of differentiation of HL-60 promyelocytic leukemia cells, expression of the cell cycle-dependent histone genes is downregulated at the level of transcription. To address the mechanism by which this regulation occurs, we examined the chromatin structure of the histone H4/n (FO108, H4FN) gene locus. Micrococcal nuclease, DNase I, and restriction enzymes show similar cleavage sites and levels of sensitivity at the H4/n locus in both proliferating and differentiated HL-60 cells. In contrast, differentiation-related activation of the cyclin-dependent kinase inhibitor p21cip1/WAF1 gene is accompanied by increased nuclease hypersensitivity. Chromatin immunoprecipitation assays of the H4/n gene reveal that acetylated histones H3 and H4 are maintained at the same levels in proliferating and postproliferative cells. Thus, the chromatin of the H4/n locus remains in an open state even after transcription ceases. Using ligation-mediated PCR to visualize genomic DNase I footprints at single-nucleotide resolution, we find that protein occupancy at the site II cell cycle element is selectively diminished in differentiated cells while the site I element remains occupied. Decreased occupancy of site II is reflected by loss of the site II binding protein HiNF-P. We conclude that H4 gene transcription during differentiation is downregulated by modulating protein interaction at the site II cell cycle element and that retention of an open chromatin conformation may be associated with site I occupancy.

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