Repurposing of Acriflavine to target Chronic Myeloid Leukemia treatment.

Repurposing of Acriflavine to target Chronic Myeloid Leukemia treatment. Curr Med Chem. 2020 Sep 08;: Authors: Nehme R, Hallal R, El Dor M, Kobeissy F, Gouilleux F, Mazurier F, Zibara K Abstract Drug repurposing has lately received increasing interest in several diseases especially in cancers due to its advantages in facilitating the development of new therapeutic strategies, by adopting a cost-friendly approach and avoiding the strict Food and Drug Administration (FDA) regulations. Acriflavine (ACF) is an FDA approved molecule that has been extensively studied since 1912 with antiseptic, trypanocidal, anti-viral, anti-bacterial and anti-cancer effects. ACF has been shown to block the growth of solid and hematopoietic tumor cells. Indeed, ACF acts as an inhibitor of various proteins including DNA-dependent protein kinases C (DNA-PKcs), topoisomerase I and II, hypoxia-inducible factor 1α (HIF-1α), in addition to its recent discovery as an inhibitor of the signal transducer and activator of transcription (STAT). Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by the expression of the constitutively active tyrosine kinase BCR-ABL. This protein allows the activation of several signaling pathways known for their role in cell proliferation and survival such as JAK/STAT pathway. CML therapy, based on tyrosine kinase inhibitors (TKIs), such as imatinib (IM), is highly effective. However, 15% of patients are refrac...
Source: Current Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Med Chem Source Type: research

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Corcos Eric Lippert Since the discovery of spliceosome mutations in myeloid malignancies, abnormal pre-mRNA splicing, which has been well studied in various cancers, has attracted novel interest in hematology. However, despite the common occurrence of spliceosome mutations in myelo-proliferative neoplasms (MPN), not much is known regarding the characterization and mechanisms of splicing anomalies in MPN. In this article, we review the current scientific literature regarding “splicing and myeloproliferative neoplasms”. We first analyse the clinical series reporting spliceosome mutations in MPN and ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
ek Vladimir Divoky Inflammatory and oncogenic signaling, both known to challenge genome stability, are key drivers of BCR-ABL-positive chronic myeloid leukemia (CML) and JAK2 V617F-positive chronic myeloproliferative neoplasms (MPNs). Despite similarities in chronic inflammation and oncogene signaling, major differences in disease course exist. Although BCR-ABL has robust transformation potential, JAK2 V617F-positive polycythemia vera (PV) is characterized by a long and stable latent phase. These differences reflect increased genomic instability of BCR-ABL-positive CML, compared to genome-stable PV with rare cytogene...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Chronic myelogenous leukemia (CML) is a clonal myeloproliferative neoplasm resulting from BCR –ABL-transformed hematopoietic stem cells. Previous research has implicated multifunctional proinflammatory cytokine...
Source: Cancer Cell International - Category: Cancer & Oncology Authors: Tags: Primary research Source Type: research
T cell cancer neoantigens are created from peptides derived from cancer-specific aberrant proteins, such as mutated and fusion proteins, presented in complex with human leukocyte antigens on the cancer cell surface. Because expression of the aberrant target protein is exclusive to malignant cells, immunotherapy directed against neoantigens should avoid “on-target, off-tumor” toxicity. The efficacy of neoantigen vaccines in melanoma and glioblastoma and of adoptive transfer of neoantigen-specific T cells in epithelial tumors indicates that neoantigens are valid therapeutic targets. Improvements in sequencing tec...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
tsch JJ Abstract Chronic myeloid leukaemia (CML) is a clonal myeloproliferative stem cell disorder characterized by the constitutively active BCR-ABL tyrosine kinase. The LIM and SH3 domain protein 1 (LASP1) has recently been identified as a novel BCR-ABL substrate and is associated with proliferation, migration, tumorigenesis and chemoresistance in several cancers. Furthermore, LASP1 was shown to bind to the chemokine receptor 4 (CXCR4), thought to be involved in mechanisms of relapse. In order to identify potential LASP1-mediated pathways and related factors that may help to further eradicate minimal residual di...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
Feasibility of tumor‑derived exosome enrichment in the onco‑hematology leukemic model of chronic myeloid leukemia. Int J Mol Med. 2019 Oct 14;: Authors: Bernardi S, Foroni C, Zanaglio C, Re F, Polverelli N, Turra A, Morello E, Farina M, Cattina F, Gandolfi L, Zollner T, Buttini EA, Malagola M, Russo D Abstract Due to the discovery of their role in intra‑cellular communications, exosomes, which carry information specific to the cell of origin, have garnered considerable attention in cancer research. Moreover, there is evidence to suggest the possibility of isolating different exosome sub‑popula...
Source: International Journal of Molecular Medicine - Category: Molecular Biology Authors: Tags: Int J Mol Med Source Type: research
Authors: Mirza MAB, Guru SA, Abdullah SM, Rizvi A, Saxena A Abstract Background: Chronic myeloid leukaemia (CML) is a myeloproliferative disorder categorized by malignant transformation of a single stem cell of hematopoietic cells. microRNAs (miRNAs) belong to transcription regulators in hematopoiesis and their altered expression associates with pathogenesis of CML. Aim: Current study aimed to access the miR-21 expression profile in CML patients and therapy response as well as its prognostic significance. Methods: 100 CML cases, 100 controls were included in study and miR-21 expression was analyzed. Overall 9.22 me...
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
In conclusion, complex translocations in unusual locations of the BCR / ABL gene appear to indicate a poor prognosis.
Source: Cancer Genetics - Category: Cancer & Oncology Source Type: research
Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the constitutive tyrosine kinase (TK) activity of the BCR-ABL1 fusion protein. Accordingly, TK inhibitors have drastically changed the d...
Source: Journal of Experimental and Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Research Source Type: research
Conclusions The discovery of JAK2V617F mutation in BCR-ABL1-negative MPNs by four different international cooperative groups in 2005 (2–5) led to significant insights on the pathogenesis of these disorders. In fact, this mutation results in a gain-of-function with activation of cytokine and growth factor receptors, and thus of the downstream JAK-STAT pathway (79, 95–98). The JAK2 point mutation in exon 12, present in a small percentage of patients with PV, is able to induce the MPN phenotype through the same pathogenic mechanism (6, 7). In 2006 the MPLW515L/K was reported in ET and PMF patients (44, 45) and d...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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