Establishment and molecular characterization of decitabine-resistant K562 cells

Journal of Cellular and Molecular Medicine
Xiang-Mei WenJ Qian

Abstract

The clinical activity of decitabine (5-aza-2-deoxycytidine, DAC), a hypomethylating agent, has been demonstrated in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients. However, secondary resistance to this agent often occurs during treatment and leads to treatment failure. It is important to clarify the mechanisms underlying the resistance for improving the efficacy. In this study, by gradually increasing concentration after a continuous induction of DAC, we established the DAC-resistant K562 cell line (K562/DAC) from its parental cell line K562. The proliferation and survival rate of K562/DAC was significantly increased, whereas the apoptosis rate was remarkably decreased than that of K562 after DAC treatment. In K562/DAC, a total of 108 genes were upregulated and 118 genes were downregulated by RNA-Seq. In addition, we also observed aberrant expression of DDX43/H19/miR-186 axis (increased DDX43/H19 and decreased miR-186) in K562/DAC cells. Ectopic expression of DDX43 in parental K562 cells rendered cells resistant to the DAC. Taken together, we successfully established DAC-resistant K562 cell line which can serve as a good model for investigating DAC resistance mechanisms, and DDX43/H19/miR-186 may be in...Continue Reading

References

Aug 3, 2002·Oncogene·Melanie Ehrlich
Mar 14, 2008·The New England Journal of Medicine·Manel Esteller
Apr 22, 2008·International Journal of Cancer. Journal International Du Cancer·Carlo Stresemann, Frank Lyko
Sep 16, 2009·Carcinogenesis·Shikhar SharmaPeter A Jones
Oct 15, 2010·Nature Biotechnology·Theresa K KellyPeter A Jones
Oct 21, 2010·CA: a Cancer Journal for Clinicians·Rodolphe Taby, Jean-Pierre J Issa
Aug 23, 2011·PloS One·Taichun QinJean-Pierre J Issa
May 9, 2012·British Journal of Haematology·Qin ChenYun Li
Dec 18, 2013·Current Opinion in Hematology·Amer M ZeidanRami S Komrokji
Apr 24, 2014·Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progrès Dans Les Recherches Sur Le Cancer·Björn Hackanson, Michael Daskalakis
Jun 6, 2014·Molecular Cancer Therapeutics·Grazia AmbrosiniGary K Schwartz
Oct 16, 2014·European Journal of Haematology·Je-Hwan LeeYoung-Don Joo
Aug 22, 2015·American Journal of Hematology·Guillermo Garcia-Manero
Jul 2, 2016·OncoTargets and Therapy·Pengfei JiangWeiguo Li
Mar 1, 2017·Frontiers in Pharmacology·Rashidah BaharudinRahman Jamal
Mar 28, 2017·Cancer Letters·Aurélie Van TongelenCharles De Smet

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
PCR
Flow

Software Mentioned

SPSS21

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukaemia & RNA

Acute myeloid leukaemia (AML) is a common hematological type of cancer. As the population ages, there has been a rise in the frequency of AML. RNA expression has been used to see if there are different genetic profiles that exist within AML and whether these may underpin the variations in survival rates. Here is the latest research on AML and RNA.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.