A genome-wide CRISPR/Cas9 screen in acute myeloid leukemia cells identifies regulators of TAK-243 sensitivity

Barghout, Samir H.; Aman, Ahmed; Nouri, Kazem; Blatman, Zachary; Arevalo, Karen; Thomas, Geethu Emily; MacLean, Neil; Hurren, Rose; Ketela, Troy; Saini, Mehakpreet; Abohawya, Moustafa; Kiyota, Taira; Al‐awar, Rima; Schimmer, Aaron D.

doi:10.1172/jci.insight.141518

Cited by 33 publications

(32 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, in a study of acute lymphoblastic leukemia, Autry et al (48) discovered that mutation of a previously unidentified gene, CELSR2, confers glucocorticoid resistance. Similarly, another CRISPR drug resistance screen found that BEND3 knockout confers resistance to antileukemia drug TAK-243 (49). Using this same strategy, CRISPR screening can also help explore the mechanism of resistance to immune cell killing.…”

Section: Crispr Screen Assay Strategiesmentioning

confidence: 95%

Applying CRISPR Screen in Diabetes Research

Peng

Morrow

2021

Diabetes

View full text Add to dashboard Cite

The CRISPR/Cas9 genome editing system has been one of the greatest scientific discoveries in the last decade. The highly efficient and precise editing ability of this technology is of great therapeutic value and benefits the basic sciences as an advantageous research tool. In recent years, forward genetic screens using CRISPR technology have been widely adopted, with genome-wide or pathway-focused screens leading to important and novel discoveries. CRISPR screens have been used primarily in cancer biology, virology, and basic cell biology, but they have rarely been applied to diabetes research. A potential reason for this is that diabetes-related research can be more complicated, often involving cross talk between multiple organs or cell types. Nevertheless, many questions can still be reduced to the study of a single cell type if assays are carefully designed. Here we review the application of CRISPR screen technology and provide perspective on how it can be used in diabetes research.

show abstract

Section: Crispr Screen Assay Strategiesmentioning

confidence: 95%

Applying CRISPR Screen in Diabetes Research

Peng

Morrow

2021

Diabetes

View full text Add to dashboard Cite

show abstract

“…A genome-wide Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) (CRISPR/Cas9) knockout screen in OCI-AML2 cells identifies the BEN domain containing 3 ( BEND3 ) as a regulator of TAK-243 sensitivity [ 179 ]. BEND3, a mediator for transcriptional repression, interacts with chromatin-modifying complexes and utilizes diverse strategies to induce repressive histones and to alter DNA methylation [ 180 ].…”

Section: Small Molecules In Amlmentioning

confidence: 99%

“…BEND3, a mediator for transcriptional repression, interacts with chromatin-modifying complexes and utilizes diverse strategies to induce repressive histones and to alter DNA methylation [ 180 ]. BEND3 knockout confers resistance to TAK-243 in vitro and in vivo [ 179 ]. TAK-243 treated BEND3 knockout cells exhibit little induction of proteotoxic stress (activating transcription factor 4 (ATF4), C/EBP Homologous Protein (CHOP), and phospho-c-Jun N-terminal kinase (p-JNK)), DNA damage (γH2AX), and apoptosis (cleaved Poly (ADP-ribose) polymerase (PARP)) markers [ 179 ].…”

Section: Small Molecules In Amlmentioning

confidence: 99%

“…BEND3 knockout confers resistance to TAK-243 in vitro and in vivo [ 179 ]. TAK-243 treated BEND3 knockout cells exhibit little induction of proteotoxic stress (activating transcription factor 4 (ATF4), C/EBP Homologous Protein (CHOP), and phospho-c-Jun N-terminal kinase (p-JNK)), DNA damage (γH2AX), and apoptosis (cleaved Poly (ADP-ribose) polymerase (PARP)) markers [ 179 ]. BEND3 knockout upregulated the ATP-binding cassette efflux transporter breast cancer resistance protein (BCRP; which mediates the resistance of numerous unrelated anticancer drugs) [ 181 , 182 , 183 ] and reduced the intracellular levels of TAK-243 [ 179 ].…”

Section: Small Molecules In Amlmentioning

confidence: 99%

See 1 more Smart Citation

Acute Myeloid Leukemia-Related Proteins Modified by Ubiquitin and Ubiquitin-like Proteins

Park

Baek

2022

IJMS

View full text Add to dashboard Cite

Acute myeloid leukemia (AML), the most common form of an acute leukemia, is a malignant disorder of stem cell precursors of the myeloid lineage. Ubiquitination is one of the post-translational modifications (PTMs), and the ubiquitin-like proteins (Ubls; SUMO, NEDD8, and ISG15) play a critical role in various cellular processes, including autophagy, cell-cycle control, DNA repair, signal transduction, and transcription. Also, the importance of Ubls in AML is increasing, with the growing research defining the effect of Ubls in AML. Numerous studies have actively reported that AML-related mutated proteins are linked to Ub and Ubls. The current review discusses the roles of proteins associated with protein ubiquitination, modifications by Ubls in AML, and substrates that can be applied for therapeutic targets in AML.

show abstract

“…out upregulated the ATP-binding cassette super-family G member 2 (ABCG2) and decreased the intracellular levels of TAK-243. Thus, ABCG2 expression could be a predictor of TAK-243 sensitivity 12 .…”

Section: Protein Metabolismmentioning

confidence: 99%

The high-performance technology CRISPR/Cas9 improves knowledge and management of acute myeloid leukemia

Mihăilă¹,

Topircean²

2021

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

View full text Add to dashboard Cite

Knowledge on acute myeloid leukemia pathogenesis and treatment has progressed recently, but not enough to provide ideal management. Improving the prognosis of acute myeloid leukemia patients depends on advances in molecular biology for the detection of new therapeutic targets and the production of effective drugs. The CRISPR/Cas9 technology allows gene insertions and deletions and it is the first step in investigating the function of their encoded proteins. Thus, new experimental models have been developed and progress has been made in understanding protein metabolism, antitumor activity, leukemic cell maintenance, differentiation, growth, apoptosis, and self-renewal, the combined pathogenetic mechanisms involved in leukemogenesis. The CRISPR/Cas9 system is used to understand drug resistance and find solutions to overcome it. The therapeutic progress achieved using the CRISPR/Cas9 system is remarkable. FST gene removal inhibited acute myeloid leukemia cell growth. Lysine acetyltransferase gene deletion contributed to decreased proliferation rate, increased apoptosis, and favored differentiation of acute myelid leukemia cells carrying MLL-X gene fusions. The removal of CD38 gene from NK cells decreased NK fratricidal cells contributing to increased efficacy of new CD38 CAR-NK cells to target leukemic blasts. BCL2 knockout has synergistic effects with FLT3 inhibitors. Exportin 1 knockout is synergistic with midostaurin treatment in acute myeloid leukemia with FLT3-ITD mutation. Using the results of CRISPR/Cas9 libraries and technology application will allow us to get closer to achieving the goal of curing acute myeloid leukemia in the coming decades.

show abstract

A genome-wide CRISPR/Cas9 screen in acute myeloid leukemia cells identifies regulators of TAK-243 sensitivity

Cited by 33 publications

References 54 publications

Applying CRISPR Screen in Diabetes Research

Applying CRISPR Screen in Diabetes Research

Acute Myeloid Leukemia-Related Proteins Modified by Ubiquitin and Ubiquitin-like Proteins

The high-performance technology CRISPR/Cas9 improves knowledge and management of acute myeloid leukemia

Contact Info

Product

Resources

About