Allogeneic stem cell transplantation (ASCT) is the only proven curative therapy for CML with cure rates of ~ 7080% in young (age <40 years) chronic-phase patients who have HLA-matched donors and undergo transplantation within 1 year of diagnosis.[5] However, the associated morbidity and mortality of ASCT is significant; furthermore, most 65%) patients do not have a suitably matched donor while older patients are often suboptimal candidates for transplantation.

An appreciation and comparison of other treatment options requires an understanding of what constitutes an efficacious therapeutic response; this is gauged using three basic parameters: hematological, cytogenetic, and molecular. Hematological remission is achieved when the blood counts and spleen size have normalized. Cytoge-netic response is quantified and graded based upon the percentage of residual Ph+ cells. Traditionally, cytogenetic response serves as the ''gold standard'' for analysis, providing an important predictor of patient survival. Once conventional hematological and cytogenetic remission has been achieved, monitoring then relies upon minimal residual disease assessment using more sensitive molecular techniques to detect the BCR-ABL fusion transcript. With successful ASCT, both hematological and cytogenetic remission are achieved and the BCR-ABL transcript is no longer detectable.

In patients who are not suitable candidates for ASCT, alternative therapies include interferon-alpha[6] and, more recently, imatinib mesylate (or Gleevec, STI571). Molecular targeted drug therapy with imatinib, a synthetic tyrosine kinase inhibitor, has shown activity in all phases of CML with substantial responses in newly diagnosed patients in chronic phase.[7-10] In an on-going randomized Phase III trial (IRIS), the observed rate of complete cytogenetic remission in newly diagnosed CML patients was 76% with imatinib vs. 15% with interferon plus Ara-C (median follow-up 18 months).[8] Although long-term outcome data are not yet available, imatinib has emerged as the therapy of choice for initial, although still noncurative, treatment of CML as the BCR-ABL fusion transcript persists at low levels. One major obstacle to treatment has been the development of therapeutic resistance, particularly in individuals with advanced

The t(9;22) translocation can result from several different breakpoints in the BCR and ABL genes, each with different chimeric fusion proteins that confer somewhat specific clinicopathological features and indicate that this translocation is not pathognomonic of CML (Fig. 1A and B). These breakpoints, indistinguishable by traditional karyotyping, can only be differentiated using molecular techniques. In each, most of ABL is juxtaposed to variable 5' portions of BCR. Whereas the breakpoint involving ABL is relatively conserved, usually arising in the intron before exon 2 (a2), the breakpoints involving BCR are more variable. Breakpoints arising in the major breakpoint cluster region (M-bcr) are by far the most common in CML. They occur after either exon 13 (e13 or b2) or exon 14 (e14 or b3), encode a p210 fusion protein, and are present in the vast majority 99%) of patients with CML.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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