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Chronic Myeloid Leukaemia in The 21st Century.

Frazer R, Irvine AE, McMullin MF - Ulster Med J (2007)

View Article: PubMed Central - PubMed

Affiliation: Department of Haematology, Centre for Cancer Research and Cell Biology, Queen's University Belfast, U Floor, Belfast City Hospital.

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Chronic Myeloid Leukaemia (CML) is a clonal, myeloproliferative disease that develops when a single, pluripotential, haemopoetic stem cell acquires the Philadelphia chromosome... The cytogenetic hallmark of CML was identified in 1973 as the reciprocal translocation t(9;22)(q34:11)... Classic CML is characterised by a reciprocal translocation between chromosomes 9 and 22... Methods for detecting MRD, should ideally have sensitivity within the 10 to 10 range, be applicable for almost all patients with the disease, provide information on the target, be inexpensive, rapid, readily standardized and disease specific... Additionally, to utilise results effectively good interlaboratory reproducibility and standardisation of reporting is essential... Unique to leukaemic cells, the BCR-ABL protein is expressed at high levels and its tyrosine kinase activity of the SH1 domain is essential for its ability to induce CML... A further characteristic of imatinib is its striking degree of specificity for the ATP binding pocket, as its effect on other cellular tyrosine kinases is negligible,... In the treatment of chronic phase CML, imatinib produces a superior and sustainable response compared to INFα... This is a highly conserved domain involved in ATP binding... Further mechanisms of secondary resistance involve over expression of BCR-ABL; acquired additional mutations, clonal evolution, that is the addition of novel chromosomal aberrations, and pharmacological mechanisms, resulting in a reduction in the quantity of available unbound imatinib, resulting in suboptimal levels of imatinib for effect,... Studies using RQ-PCR have shown that an early reduction of BCR-ABL gene transcript levels can predict a subsequent cytogenetic response in CML,... Studies have investigated the consequences of HHT in combination with INFα or low dose cytarabine... When in dual therapy or in triple combination therapy, complete haematologic and complete cytogenetic responses equivalent to or superior to HHT single therapy have been shown, suggesting improved survival rates compared to HHT alone–... Studies have shown dose dependant growth inhibition and a pro-apoptotic effect when CML cells were treated with clinically tolerable levels of As2O3... A significant decline in BCR-ABL protein levels was also noted, and did not coincide with reduction in any other cellular proteins, suggesting specificity of this treatment.

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BCR-ABL signalling pathways.
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fig2: BCR-ABL signalling pathways.

Mentions: BCR-ABL has several substrates and impacts on key signalling pathways resulting in the CML phenotype6. The net result is deregulated cellular proliferation and development of growth factor independence, decreased adherence of the leukaemic cells to the bone marrow stroma, and a reduced apoptotic response to mutagenic stimuli (Figs 1 and 2)1.


Chronic Myeloid Leukaemia in The 21st Century.

Frazer R, Irvine AE, McMullin MF - Ulster Med J (2007)

BCR-ABL signalling pathways.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1940291&req=5

fig2: BCR-ABL signalling pathways.
Mentions: BCR-ABL has several substrates and impacts on key signalling pathways resulting in the CML phenotype6. The net result is deregulated cellular proliferation and development of growth factor independence, decreased adherence of the leukaemic cells to the bone marrow stroma, and a reduced apoptotic response to mutagenic stimuli (Figs 1 and 2)1.

View Article: PubMed Central - PubMed

Affiliation: Department of Haematology, Centre for Cancer Research and Cell Biology, Queen's University Belfast, U Floor, Belfast City Hospital.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Chronic Myeloid Leukaemia (CML) is a clonal, myeloproliferative disease that develops when a single, pluripotential, haemopoetic stem cell acquires the Philadelphia chromosome... The cytogenetic hallmark of CML was identified in 1973 as the reciprocal translocation t(9;22)(q34:11)... Classic CML is characterised by a reciprocal translocation between chromosomes 9 and 22... Methods for detecting MRD, should ideally have sensitivity within the 10 to 10 range, be applicable for almost all patients with the disease, provide information on the target, be inexpensive, rapid, readily standardized and disease specific... Additionally, to utilise results effectively good interlaboratory reproducibility and standardisation of reporting is essential... Unique to leukaemic cells, the BCR-ABL protein is expressed at high levels and its tyrosine kinase activity of the SH1 domain is essential for its ability to induce CML... A further characteristic of imatinib is its striking degree of specificity for the ATP binding pocket, as its effect on other cellular tyrosine kinases is negligible,... In the treatment of chronic phase CML, imatinib produces a superior and sustainable response compared to INFα... This is a highly conserved domain involved in ATP binding... Further mechanisms of secondary resistance involve over expression of BCR-ABL; acquired additional mutations, clonal evolution, that is the addition of novel chromosomal aberrations, and pharmacological mechanisms, resulting in a reduction in the quantity of available unbound imatinib, resulting in suboptimal levels of imatinib for effect,... Studies using RQ-PCR have shown that an early reduction of BCR-ABL gene transcript levels can predict a subsequent cytogenetic response in CML,... Studies have investigated the consequences of HHT in combination with INFα or low dose cytarabine... When in dual therapy or in triple combination therapy, complete haematologic and complete cytogenetic responses equivalent to or superior to HHT single therapy have been shown, suggesting improved survival rates compared to HHT alone–... Studies have shown dose dependant growth inhibition and a pro-apoptotic effect when CML cells were treated with clinically tolerable levels of As2O3... A significant decline in BCR-ABL protein levels was also noted, and did not coincide with reduction in any other cellular proteins, suggesting specificity of this treatment.

Show MeSH