Cytogenetic Clonal Evolution Ce

The acquisition of nonrandom karyotypic abnormalities in addition to the Ph chromosome is referred to as CE. CE is strongly associated with disease progression, occurring in more than 50% of patients with blastic transformation.32 Although many different chromosomal abnormalities have been reported, there are a few specific changes that account for the majority of cases.33 Hyperdiploid karyotypes predominate, most commonly trisomy 8, 19, 21, or a second Ph chromosome. Another frequent finding is isochromosome 17, while monosomy 7, loss of the Y chromosome, and reciprocal translocations, such as t(3;21)(q21;q26), are relatively rare. Progressively more abnormalities are often acquired during further disease progression. Intriguingly, the sequence of acquisition of these additional changes is apparently nonrandom, following certain "routes" of CE,33 and there are geographical and ethnic differences, whose etiology is not under-stood.34 Events like t(3;21)(q21;q26) that involves the EVI-1 gene, a transcription factor, may conceivably dysregulate myeloid cell differentiation, a key feature of blastic transformation, and thus explain the pheno-type of blast crisis compared to chronic phase. However, in most instances, it is not known how the recurrent chromosomal changes may contribute to the loss of cell differentiation that characterizes blast crisis. It should be noted that nonrandom chromosomal abnormalities have been detected in the Ph-chro-mosome-negative cells of some patients, with a complete cytogenetic response to imatinib.35 This yet unexplained phenomenon should not be referred to as CE.

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