Isfahan University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Development of Epigenetic Modifiers With Therapeutic Potential in Fms-Related Tyrosine Kinase 3/Internal Tandem Duplication (Flt3/Itd) Acute Myeloid Leukemia and Other Blood Malignancies Publisher



Carullo G1 ; Rossi S1 ; Giudice V2 ; Pezzotta A3 ; Chianese U4 ; Scala P2 ; Carbone S3 ; Fontana A1 ; Panzeca G1 ; Pasquini S5 ; Contri C6 ; Gemma S1 ; Ramunno A7 ; Saponara S8 Show All Authors
Authors
  1. Carullo G1
  2. Rossi S1
  3. Giudice V2
  4. Pezzotta A3
  5. Chianese U4
  6. Scala P2
  7. Carbone S3
  8. Fontana A1
  9. Panzeca G1
  10. Pasquini S5
  11. Contri C6
  12. Gemma S1
  13. Ramunno A7
  14. Saponara S8
  15. Galvani F9
  16. Lodola A9
  17. Mor M9
  18. Benedetti R4, 10
  19. Selleri C2
  20. Varani K6
  21. Butini S1
  22. Altucci L4, 10, 11
  23. Vincenzi F6
  24. Pistocchi A3
  25. Campiani G1, 12
Show Affiliations
Authors Affiliations
  1. 1. Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy
  2. 2. Department of Medicine, Surgery, Dentistry “Scuola Medica Salernitana”, University of Salerno, Via S. Allende, SA, Baronissi, 84081, Italy
  3. 3. Department of Medical Biotechnology and Translational Medicine, University of Milan, LITA, Fratelli Cervi 93, Segrate, MI 20054, Italy
  4. 4. Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via de Crecchio 7, Naples, 80138, Italy
  5. 5. Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Borsari 46, Ferrara, 44121, Italy
  6. 6. Department of Translational Medicine, University of Ferrara, Via Borsari 46, Ferrara, 44121, Italy
  7. 7. Department of Pharmacy, University of Salerno, Giovanni Paolo II, 132, Fisciano, SA 84084, Italy
  8. 8. Department of Life Sciences, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy
  9. 9. Department of Food and Drug, University of Parma, Parco Area delle Scienze 27/A, Parma, 43124, Italy
  10. 10. Program of Medical Epigenetics, Vanvitelli Hospital, Naples, 80138, Italy
  11. 11. Biogem Institute of Molecular and Genetic Biology, Ariano Irpino, 83031, Italy
  12. 12. Bioinformatics Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, 81746-7346, Iran

Source: ACS Pharmacology and Translational Science Published:2024


Abstract

Blood cancers encompass a group of diseases affecting the blood, bone marrow, or lymphatic system, representing the fourth most commonly diagnosed cancer worldwide. Leukemias are characterized by the dysregulated proliferation of myeloid and lymphoid cells with different rates of progression (acute or chronic). Among the chronic forms, hairy cell leukemia (HCL) is a rare disease, and no drugs have been approved to date. However, acute myeloid leukemia (AML) is one of the most aggressive malignancies, with a low survival rate, especially in cases with FLT3-ITD mutations. Epigenetic modifications have emerged as promising strategies for the treatment of blood cancers. Epigenetic modulators, such as histone deacetylase (HDAC) inhibitors, are increasingly used for targeted cancer therapy. New hydroxamic acid derivatives, preferentially inhibiting HDAC6 (5a-q), were developed and their efficacy was investigated in different blood cancers, including multiple myeloma (MM), HCL, and AML, pointing out their pro-apoptotic effect as the mechanism of cell death. Among the inhibitors described, 5c, 5g, and 5h were able to rescue the hematopoietic phenotype in vivo using the FLT3-ITD zebrafish model of AML. 5c (leuxinostat) proved its efficacy in cells from FLT3-ITD AML patients, promoting marked acetylation of α-tubulin compared to histone H3, thereby confirming HDAC6 as a preferential target for this new class of hydroxamic acid derivatives at the tested doses. © 2024 American Chemical Society.
Related Docs
View other Related Docs
1. Targeting Relevant Hdacs to Support the Survival of Cone Photoreceptors in Inherited Retinal Diseases: Identification of a Potent Pharmacological Tool With in Vitro and in Vivo Efficacy, Journal of Medicinal Chemistry (2024)
2. A Novel Potent Class I Hdac Inhibitor Reverses the Stat4/P66shc Apoptotic Defect in B Cells From Chronic Lymphocytic Leukemia Patients, Biomedicine and Pharmacotherapy (2024)
3. Quizartinib: A New Hope in Acute Myeloid Leukemia, an Applied Comprehensive Review, Future Oncology (2024)
4. Microrna Dysregulation and Its Impact on Apoptosis-Related Signaling Pathways in Myelodysplastic Syndrome, Pathology Research and Practice (2024)
5. Discovery of Novel Hit Compounds As Potential Hdac1 Inhibitors: The Case of Ligand- and Structure-Based Virtual Screening, Computers in Biology and Medicine (2021)
6. Effects of Hsa-Pir-32877 Suppression With Antisense Lna Gapmers on the Proliferation and Apoptosis of Human Acute Myeloid Leukemia Cells, International Journal of Molecular and Cellular Medicine (2023)
7. H19: A Regulatory Biomarker With Prognostic Value in Leukemias, Eurasian Journal of Medicine and Oncology (2019)
8. Metalloenzyme Inhibitors Against Zoonotic Infections: Focus on Leishmania and Schistosoma, ACS Infectious Diseases (2024)
Experts (# of related papers)
View all Related Experts
Mohammadreza Sharifi (7)
Behrooz Ghezelbash (2)
Other Related Docs
9. Transcription Analysis of a Histones Modifiers Panel Coupled With Critical Tumor Suppressor Genes Displayed Frequent Changes in Patients With Aml.: Mrna Levels of Histones Modifiers and Tsgs in Aml, Current Research in Translational Medicine (2021)
10. Computer-Driven Development of an in Silico Tool for Finding Selective Histone Deacetylase 1 Inhibitors, Molecules (2020)
11. Emerging Roles of Jmjd3 in Cancer, Clinical and Translational Oncology (2022)
12. Apoptosis Induction in Acute Promyelocytic Leukemia Cells Through Upregulation of Cebpα by Mir-182 Blockage, Molecular Biology Research Communications (2018)
13. Inducing Cell Proliferative Prevention in Human Acute Promyelocytic Leukemia by Mir-182 Inhibition Through Modulation of Casp9 Expression, Biomedicine and Pharmacotherapy (2017)
14. Traceability and Authentication in Agri-Food Production: A Multivariate Approach to the Characterization of the Italian Food Excellence Elephant Garlic (Allium Ampeloprasum L.), a Vasoactive Nutraceutical, Food Chemistry (2024)
15. Reduce Proliferation of Human Bone Marrow Cells From Acute Myeloblastic Leukemia With Minimally Differentiation by Blocking Lncrna Pvt1, Clinical and Translational Oncology (2020)
16. Chitosan As Possible Inhibitory Agents and Delivery Systems in Leukemia, Cancer Cell International (2021)
17. Antiproliferative Effect of Upregulation of Hsa-Let-7C-5P in Human Acute Erythroleukemia Cells, Cytotechnology (2018)
18. Implementation of Docking, Molecular Dynamics and Free Energy to Investigate Drug Potency of Novel Bcr-Ablt315i Inhibitors As an Alternative to Ponatinib, Computational Toxicology (2021)
19. Inducing Apoptosis and Decreasing Cell Proliferation in Human Acute Promyelocytic Leukemia Through Regulation Expression of Casp3 by Let-7A-5P Blockage, Indian Journal of Hematology and Blood Transfusion (2018)
20. Microrna in Leukemia: Tumor Suppressors and Oncogenes With Prognostic Potential, Journal of Cellular Physiology (2019)
21. Induction of Apoptosis and Necrosis in Human Acute Erythroleukemia Cells by Inhibition of 47Tlong Non-Coding Rna Pvt1, Molecular Biology Research Communications (2018)