Clinical significance of low protein phosphatase-1 activity of blasts in acute myelogenous leukemia with high white cell counts

We have previously shown that protein phosphatase-1 (PP1) is the most abundant Ser/Thr phosphatase in human adult primary leukemic cells. To determine the clinical importance of PP expression, we compared PP1 activity of leukemic blasts with other putative prognostic factors in 46 patients with acute myelogenous leukemia (AML) who were treated with remission induction chemotherapy. PP1 was ubiquitously but differently expressed in various FAB subtypes (M1-M5), although PPI activity was significantly higher in blasts of AML-M4 than in AML-M2. PP1 activity was significantly lower in elderly patients greater than or equal to 55 years (P = 0.005), and in those with high white cell counts greater than or equal to 100,000/mul (P = 0.039) at initial diagnosis. Correlation was observed between PP1 activity (<0.15 vs <greater than or equal to>0.15 nmol/min/10(8) cells) and prognosis of AML patients. Eleven of 46 patients with less than 0.15 nmol/min/10(8) cells (low PP1 activity group) had significantly lower overall survival than those with greater than or equal to0.15 nmol/min/10(8) cells (high PP1 activity group). The median overall survival was 8 months for patients with low PP1 activity compared to 27 months for those with high PP1 activity in their AML cells. Multivariate analysis using Cox's proportional hazard model showed that low PP1 activity significantly contributed to prognosis. This preliminary study suggests that low PP1 activity may be associated with shortened survival time for AML patients with high white cell counts.