Abstract
Abstract 4249
Ki-67 and caspase-3 are widely accepted as proliferation and apoptosis markers. We recently reported that Ki-67 can be detected as a circulating protein (cKi-67) in the plasma of patients with acute lymphoblastic leukemia (ALL), and that higher levels correlated with more aggressive disease. Here we investigated the levels of cKi-67 in patients with chronic myeloid leukemia (CML). We also evaluated the level of apoptosis in CML as determined by plasma levels of caspase-3 activity. The study included 127 CML patients: 81 in chronic phase and 46 in accelerated phase/blast crisis. cKi-67 levels were determined with an electro-chemiluminescence-based immunoassay. Apoptosis was determined by measuring caspase-3 activity (DEVD) in the plasma using a standard enzymatic fluorogenic assay. Patients with CML had significantly (P<0.0001) higher levels of cKi-67 and caspase-3 activity than normal control (n = 96). However, median (range) cKi-67 levels did not differ significantly between CML patients in chronic phase (523 [73-5857] ng/mL) and those in accelerated/blast crisis phase (710 [100-3530] ng/mL), nor did caspase-3 activity: 12.2 (6.1-29.1) pmol/min the chronic phase group and 12.2 (range=6.6-17.9) pmol/min in the accelerated/blast crisis group. The median of cKi-67 and caspase-3 in the healthy control group was 353.06 and 8.19, respectively and range 35.76-2830.65 ng/ul and 4.54-34.30 pmol/min, respectively. Neither cKi-67 level nor caspase-3 activity correlated with white cell count or blast count in the chronic phase or in the accelerated/blast crisis phase. There was no correlation between cKi-67 or caspase-3 levels and response to imatinib therapy. However, patients in the chronic phase with high levels of cKi-67 (>354 ng/mL) had significantly longer survival than did those with lower levels (P=0.003); cKi-67 levels were not associated with outcome in accelerated/blast phase CML. Caspase-3 activity did not correlate with outcome in chronic or accelerated/blast phase patients. In conclusion, cell proliferation and apoptosis as determined by plasma cKi-67 level and caspase-3 activity are elevated in CML, but higher levels of cKi-67 unexpectedly correlated with longer survival in chronic phase CML. Although the cause for this is unknown, it is possible that higher levels of cKi-67 reflect that more stem cells are in cell cycle, and this may make them more susceptible to therapy.
No relevant conflicts of interest to declare.
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