|
|
Properties of bcr-abl transformed mouse cell lines
Fliegl, Monika
At present, chronic myeloid leukemia (CML) is one of the best understood oncological disorders at the molecular level. Its development is closely related to the translocation between chromosomes 9 and 22 that leads to the formation of the bcr-abl fusion gene encoding Bcr-Abl fusion protein. This gene modification results in an undesirable increase of the activity of the tyrosine kinase (TKA) encoded by the abl gene. After the introduction of imatinib mesylate and other tyrosine kinase inhibitors (TKI), referred to as the second generation TKI, the quality of life and the survival of patients with CML has greatly improved. Current drug treatment stops the progression of the disease and induces a remission; however, it only rarely, if ever, results in a cure. One of the main reasons is that cancer cells do not behave passively during the treatment. Frequently, the mutations of the gene lead to the selection of a clone, that is pharmacotherapy-resistant; or to an amplification of the bcr- abl. fusion gene. Furthermore, modern drug therapy based on TKIs does not eradicate tumor stem cells, which are the source of the leukemia relapse. Currently, the only possibility of curing CML is transplantation of allogeneic hematopoietic stem cells. The weaknesses of this therapeutic approach include scarcity of...
|
|
|
Properties of bcr-abl transformed mouse cell lines
Fliegl, Monika ; Vonka, Vladimír (advisor) ; Hejnar, Jiří (referee) ; Hirsch, Ivan (referee)
At present, chronic myeloid leukemia (CML) is one of the best understood oncological disorders at the molecular level. Its development is closely related to the translocation between chromosomes 9 and 22 that leads to the formation of the bcr-abl fusion gene encoding Bcr-Abl fusion protein. This gene modification results in an undesirable increase of the activity of the tyrosine kinase (TKA) encoded by the abl gene. After the introduction of imatinib mesylate and other tyrosine kinase inhibitors (TKI), referred to as the second generation TKI, the quality of life and the survival of patients with CML has greatly improved. Current drug treatment stops the progression of the disease and induces a remission; however, it only rarely, if ever, results in a cure. One of the main reasons is that cancer cells do not behave passively during the treatment. Frequently, the mutations of the gene lead to the selection of a clone, that is pharmacotherapy-resistant; or to an amplification of the bcr- abl. fusion gene. Furthermore, modern drug therapy based on TKIs does not eradicate tumor stem cells, which are the source of the leukemia relapse. Currently, the only possibility of curing CML is transplantation of allogeneic hematopoietic stem cells. The weaknesses of this therapeutic approach include scarcity of...
|
|
|
Properties of bcr-abl transformed mouse cell lines
Fliegl, Monika
At present, chronic myeloid leukemia (CML) is one of the best understood oncological disorders at the molecular level. Its development is closely related to the translocation between chromosomes 9 and 22 that leads to the formation of the bcr-abl fusion gene encoding Bcr-Abl fusion protein. This gene modification results in an undesirable increase of the activity of the tyrosine kinase (TKA) encoded by the abl gene. After the introduction of imatinib mesylate and other tyrosine kinase inhibitors (TKI), referred to as the second generation TKI, the quality of life and the survival of patients with CML has greatly improved. Current drug treatment stops the progression of the disease and induces a remission; however, it only rarely, if ever, results in a cure. One of the main reasons is that cancer cells do not behave passively during the treatment. Frequently, the mutations of the gene lead to the selection of a clone, that is pharmacotherapy-resistant; or to an amplification of the bcr- abl. fusion gene. Furthermore, modern drug therapy based on TKIs does not eradicate tumor stem cells, which are the source of the leukemia relapse. Currently, the only possibility of curing CML is transplantation of allogeneic hematopoietic stem cells. The weaknesses of this therapeutic approach include scarcity of...
|
guest ::
