Validation of a Drosophila model of wild type and T315I mutated BCR-ABL1 in chronic myeloid leukemia: An effective platform for treatment screening.

In this study, we expressed human BCR-ABL1p210 and the resistant BCR-ABL1p210/T315I fusion oncogenes in Drosophila eyes. Expression of BCR-ABL1p210/T315I resulted in severe distortion of the ommatidial architecture of adult eyes and with more prominent rough eye phenotype compared to milder phenotypes in BCR-ABL1p210 reflecting a stronger oncogenic potential of the mutant. We then assessed the efficacy of the currently used tyrosine kinase inhibitors in BCR-ABL1p210 and BCR-ABL1p210/T315I expressing flies. Treatment of BCR-ABL1p210 expressing flies with potent kinase inhibitors (dasatinib and ponatinib) resulted in the rescue of ommatidial loss and restoration of normal development. Taken together, we provide chronic myeloid leukemia tailored BCR-ABL1p210 and BCR-ABL1p210/T315I fly model which can be used to test new compounds with improved therapeutic indices. PMID: 31101753 [PubMed - as supplied by publisher]
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research

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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
This report discusses the challenges associated with the management of newly diagnosed chronic phase CML in a patient with intolerance to multiple TKI therapies. PMID: 31091066 [PubMed]
Source: Journal of the National Comprehensive Cancer Network : JNCCN - Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research
G, Sanogo I Abstract INTRODUCTION: The diagnosis of chronic myeloid leukemia is based on the presence of translocation t(9,22). Additional cytogenetic abnormalities may exist at diagnosis and have prognostic value. The authors evaluated the relationship between these additional chromosomal abnormalities, clinical presentation, and therapeutic response. METHOD: In a retrospective and comparative study from 2005 to 2015, at Yopougon university hospital, 51 cases of myeloid leukemia were selected, including 22 cases with additional chromosomal abnormalities. RESULTS: Thirteen types of additional Ph1 abnorma...
Source: Bulletin du Cancer - Category: Cancer & Oncology Authors: Tags: Bull Cancer Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study was supported by the Shanghai Sailing Program [grant number 17YF1425200, 2017]; Chinese National Natural Science Funding [grant number 81702249, 2017]; Science and Technology Commission of Shanghai Municipality [grant number 17511103403, 2017]; The funder has no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments We acknowledge the ex...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, the high structural diversity of these compounds pinpoints the significant range of inhibition strategies that can be conceived to target the class I methyltransferases. Although the structural details of the various members of this family are unique, the success stories of drug design for several enzymes belonging to this family portends the likely achievement of discovering potent and selective inhibitors of METTL3/METTL14. Author Contributions AF and AP wrote the manuscript. ZI revised and edited manuscript and prepared figures. Funding This work was supported by Associazione Italiana Ricerca sul Canc...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Abstract Chromosomal translocation occurs in some cancer cells, resulting in the expression of aberrant oncogenic fusion proteins that include BCR-ABL in chronic myelogenous leukemia (CML). Inhibitors of ABL tyrosine kinase, such as imatinib and dasatinib, exhibit remarkable therapeutic effects, although emergence of drug resistance hampers the therapy during long-term treatment. An alternative approach to treat CML is to downregulate expression of the BCR-ABL protein. Recently, we have devised a protein knockdown system by hybrid molecules named Specific and Nongenetic inhibitor of apoptosis protein [IAP]-depende...
Source: Chemical and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Chem Pharm Bull (Tokyo) Source Type: research
Philadelphia (Ph) chromosome results from the reciprocal translocation t(9;22)(q34.1;q11.2) and is diagnostic for chronic myeloid leukemia (CML). However, this translocation is also found in acute lymphoid leu...
Source: BMC Cancer - Category: Cancer & Oncology Authors: Tags: Case report Source Type: research
Conclusion: Mutation testing is recommended for choosing various tyrosine kinase inhibitors (TKIs) to optimize outcomes for both cases of treatment failure or suboptimal response to imatinib. Therefore, detection of T315I mutation in CML patients are clinically useful in the selection of appropriate treatment strategies to prevent disease progression. PMID: 30583336 [PubMed - in process]
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
Cytogenetic diagnostic analysis has been inexorably tied to the understanding of leukemic disorders since Rowley first associated the presence of the 9;22 translocation with chronic myeloid leukemia [1]. Furthermore, karyotyping of leukemia cells has served for decades as an essential clinical tool for improved diagnosis, risk stratification and treatment selection. Diagnostic testing has progressed over the last several decades and has evolved from cytogenetic and FISH to chromosomal microarray analysis (CMA) and sequencing.
Source: Cancer Genetics and Cytogenetics - Category: Genetics & Stem Cells Authors: Source Type: research
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