1,3-Butadiene metabolite 1,2,3,4 diepoxybutane induces DNA adducts and micronuclei but not t(9;22) translocations in human cells.

1,3-Butadiene metabolite 1,2,3,4 diepoxybutane induces DNA adducts and micronuclei but not t(9;22) translocations in human cells. Chem Biol Interact. 2019 Aug 15;:108797 Authors: Walker VE, Degner A, Carter EW, Nicklas JA, Walker DM, Tretyakova N, Albertini RJ Abstract Epidemiological studies of 1,3-butadiene (BD) exposures have reported a possible association with chronic myelogenous leukemia (CML), which is defined by the presence of the t(9;22) translocation (Philadelphia chromosome) creating an oncogenic BCR-ABL fusion gene. Butadiene diepoxide (DEB), the most mutagenic of three epoxides resulting from BD, forms DNA-DNA crosslink adducts that can lead to DNA double-strand breaks (DSBs). Thus, a study was designed to determine if (±)-DEB exposure of HL60 cells, a promyelocytic leukemia cell line lacking the Philadelphia chromosome, can produce t(9;22) translocations. In HL60 cells exposed for 3 h to 0-10 μM DEB, overlapping dose-response curves suggested a direct relationship between 1,4-bis-(guan-7-yl)-2,3-butanediol crosslink adduct formation (R = 0.977, P = 0.03) and cytotoxicity (R = 0.961, P = 0.002). Experiments to define the relationships between cytotoxicity and the induction of micronuclei (MN), a dosimeter of DNA DSBs, showed that 24 h exposures of HL60 cells to 0-5.0 μM DEB caused significant positive correlations between the concentration and (i) the degree of cytotoxicity (R = 0.998, p = ...
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Tags: Chem Biol Interact Source Type: research

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Abstract Mutation and translocation of fibroblast growth factor receptors often lead to aberrant signaling and cancer. This work focuses on the t(8;22)(p11;q11) chromosomal translocation which creates the BCR-FGFR1 fusion protein. This fusion occurs in stem cell leukemia/lymphoma, which can progress to atypical chronic myeloid leukemia, acute myeloid leukemia, or B-Cell lymphoma. This work focuses on biochemical characterization of BCR-FGFR1 and identification of novel therapeutic targets. The tyrosine kinase activity of FGFR1 is required for biological activity as shown using transformation assays, IL-3 independe...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Publication date: Available online 15 August 2019Source: Chemico-Biological InteractionsAuthor(s): Vernon E. Walker, Amanda Degner, Elizabeth W. Carter, Janice A. Nicklas, Dale M. Walker, Natalia Tretyakova, Richard J. AlbertiniAbstractEpidemiological studies of 1,3-butadiene (BD) exposures have reported a possible association with chronic myelogenous leukemia (CML), which is defined by the presence of the t(9;22) translocation (Philadelphia chromosome) creating an oncogenic BCR-ABL fusion gene. Butadiene diepoxide (DEB), the most mutagenic of three epoxides resulting from BD, forms DNA-DNA crosslink adducts that can lead ...
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research
The Philadelphia (Ph) chromosome, resulting from the t(9;22)(q34;q11) translocation, can be found in chronic myeloid leukemia (CML) as well as in a subset of acute lymphoblastic leukemias (ALL). The deregulate...
Source: Journal of Hematology and Oncology - Category: Hematology Authors: Tags: Review 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
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
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: The recurrence of splenomegaly in this patient following single agent RUX indicates emergence of novel BCR-ABL1+ clone. While single agent imatinib temporarily normalized the splenomegaly and leukocytosis for several months, MF phenotype reoccurred. Splenomegaly resolved completely in 8 weeks with the addition of very low dose RUX to standard dose imatinib, providing the first clinical observation of in vivo synergism of RUX and imatinib. We are investigating serial samples during her course, which will be presented at the meeting. The analysis of a single clone demonstrate that BCR-ABL1 mutation did not occur ...
Source: Blood - Category: Hematology Authors: Tags: 634. Myeloproliferative Syndromes: Clinical Source Type: research
Conclusions: The Real-timePCR, because of its specificity and sensitivity, can be considered the most used technique in routine diagnosis and investigation of MRD of CML patients.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 631. Chronic Myeloid Leukemia: Biology and Pathophysiology, excluding Therapy Source Type: research
Conclusion: Patients with relapsed/refractory lymphoid blast phase CML should receive directed salvage therapies. This case report demonstrates that failure of one line of directed therapy does not predict for future failures.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 632. Chronic Myeloid Leukemia: Therapy Source Type: research
ConclusionCML classification using different features such as Ph and ACAs can play a decisive role in the evaluation of treatment responses in patients, for example, CML patients with Ph negative and monosomy 7 develop MDS or CML patient –Y and extra copy of Ph have a good response to tyrosine kinase inhibitors, therefore, classifications according to Ph and ACAs play an important role in choosing better treatment protocols and therapeutic strategies. Karyotype analysis in CML patients with complex karyotype shows unrandom pattern so ACAs can be great clue in medical guidelines.
Source: Journal of Cellular Physiology - Category: Cytology Authors: Tags: REVIEW ARTICLE Source Type: research
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