Evidence map›Paper›PMID 38252348›Full record

ArticleMolecular biology reports2024

Combinatorial targeting of telomerase and DNA-PK induces synergistic apoptotic effects against Pre-B acute lymphoblastic leukemia cells.

Maryam Katoueezadeh, Parisa Maleki, Seyedeh Atekeh Torabizadeh, Alireza Farsinejad, Roohollah Mirzaee Khalilabadi, Hajar Mardani Valandani, Ismaila Olanrewaju Nurain, Muhammad Hossein Ashoub, Ahmad Fatemi

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Article in Molecular biology reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
3.0field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 13 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Maryam KatoueezadehStudent Research Committee, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Parisa MalekiStudent Research Committee, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Seyedeh Atekeh TorabizadehPharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Alireza FarsinejadDepartment of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Roohollah Mirzaee KhalilabadiDepartment of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Hajar Mardani ValandaniDepartment of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Ismaila Olanrewaju NurainPostdoctoral Research Fellow, Faculty of Applied Health Sciences, Brock University, St. Catharines, ON, Canada.
Muhammad Hossein AshoubDepartment of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Ahmad FatemiCellular and Molecular Research Center, Gerash University of Medical Sciences, Gerash, Iran. ahmad.fatemi2@gmail.com.
Kerman University of Medical Sciences · IRBrock University · CAGerash University of Medical Sciences · IR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDue to the high demand for novel approaches for leukemia-targeted therapy, this study investigates the impact of DNA-PK inhibitor NU7441 on the sensitivity of pre-B ALL cells to the telomerase inhibitor MST-312.

methodsThe study involved NALM-6 cells treated with MST-312 and NU7441, assessing their viability and metabolic activity using trypan blue and MTT assays. The study also evaluated apoptosis, gene expression changes, and DNA damage using flow cytometry, qRT-PCR, and micronucleus assays. The binding energy of MST-312 in the active site of telomerase was calculated using molecular docking.

resultsThe study's findings revealed a synergistic decline in both cell viability and metabolic activity in NALM-6 cells when exposed to the combined treatment of MST-312 and NU7441, and this decrease occurred without any adverse effects on healthy PBMC cells. Furthermore, the combination treatment exhibited a significantly higher induction of apoptosis than treatment with MST-312 alone, as observed through flow cytometry assay. qRT-PCR analysis revealed that this enhanced apoptosis was associated with a notable downregulation of Bcl-2 expression and an upregulation of Bax gene expression. Moreover, the combination therapy decreased expression levels of hTERT and c-Myc genes. The micronucleus assay indicated that the combination treatment increased DNA damage in NALM-6 cells. Also, a good conformation between MST-312 and the active site of telomerase was revealed by docking data.

conclusionsThe study suggests that simultaneous inhibition of telomerase and DNA-PK in pre-B ALL presents a novel targeted therapy approach.

Indexed as

BenzamidesPrecursor B-Cell Lymphoblastic Leukemia-LymphomaTelomeraseDNADNA-Activated Protein KinaseHumansLeukocytes, MononuclearMolecular Docking SimulationBenzamidesDNADNA-Activated Protein KinaseMST 312TelomeraseDNA-PKMST-312NU7441Pre-B ALLTelomerase

Identifiers

PMID38252348
OpenAlexW4391109240

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.