Leukemia & lymphoma
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Leukemia & lymphoma · Jul 2009
New mutations detected by denaturing high performance liquid chromatography during screening of exon 6 bcr-abl mutations in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors.
Point mutations within the ABL kinase domain are the most frequent mechanism for reactivation of kinase activity of the BCR-ABL gene and have been associated with clinical resistance to tyrosine kinase (TK) inhibitors in patients with CML, conferring a poor prognosis. T315I (Treonine-->Isoleucine) is a mutation in the exon 6 of BCR-ABL gene that makes the protein resistant to kinase inhibitors currently used for treating CML. Denaturing High-performance liquid chromatography (D-HPLC) allows for high throughput mutation screening. ⋯ D-HPLC is a practical and sensitive method for routine clinical monitoring for emergence of kinase domain mutations and may be useful for optimising therapy in CML. The screening of mutations in exon 6 is clinically relevant, once the presence of mutations confers a poor outcome. Early detection of emerging mutant clones may help in decision-making for alternative treatment.
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Leukemia & lymphoma · Jul 2009
B cell activator factor and a proliferation-inducing ligand at the cross-road of chronic lymphocytic leukemia and autoimmunity.
The combination of the neoplastic accumulation of mature B lymphocytes with the presence of autoimmune phenomena is a characteristic finding in chronic B cell lymphoproliferative disorders, particularly chronic lymphocytic leukemia. Identification of mechanisms linking neoplasia to the autoimmune defects is important for a better understanding and improving the treatment of these conditions. ⋯ In addition, BAFF and APRIL are crucial in B cell development and homeostasis particularly via the activation of NF-kappaB pathway-mediated survival signals. These two proteins, therefore, constitute a paradigm of pathophysiological defects linking neoplasia and autoimmunity, thereby providing a better understanding of chronic B cell lymphoproliferative disorders.