Determination of the in vivo effects of prednisone on Bcl-2 family protein expression in childhood acute lymphoblastic leukemia.

Glucocorticoid resistance is often associated with treatment failure in children with acute lymphoblastic leukaemia (ALL) but the underlying molecular mechanisms are still unclear. In 30 consecutive children with ALL treated with prednisone we determined changes in the expression of Bcl-2, Bax and Bcl-xl proteins in leukemic lymphoblasts and related these to clinical features and rate of prednisone-induced apoptosis. The apoptotic index increased after prednisone therapy in 24 of the 30 patients. At diagnosis, we detected expression of Bcl-2 and Bcl-xl protein in 28 samples, while Bax expression protein was detected in 21 of the 30 patients. Prednisone treatment induced a decrease in Bcl-2 and Bcl-xl levels in 17 and 16 of the 28 patients, respectively, while Bax protein increased in 14 of the 21 patients. Twenty of the 30 patients studied were considered to be good prednisone responders, whereas 10 were poor responders. We observed a statistically significant decrease only for Bcl-xl protein expression in T phenotype ALL, in the poor responder group and in patients with >20000/mm(3) white cell count (WBC) at diagnosis. These data suggest a role of Bcl-xl in the mechanisms of protection of leukemic cells from apoptosis induced by glucocorticoids (GCs).

Compensatory hypertrophy and progressive renal damage in children nephrectomized for Wilms' Tumor.

Clinical, biochemical, and sonographic evaluation of the remaining kidney function and size was performed in 34 patients, 12 males and 22 females, ages 2.1-19.6 years, nephrectomized (NP) for Wilms' tumor (WT) at least 2 years before (mean 8.6). All patients had normal blood pressure and serum bicarbonates. Two of them had microhematuria, four proteinuria 4 mg/m2/hr, and 11 microalbuminuria (MA) > 20 mg/24 hr. Only one patient had reduced creatinine clearance and maximum bipolar length (MBL) as well as kidney volume (KV) < 100% of expected. In the other patients, average MBL was 128 +/- 11% (P = 0.0001). MBL, but not KV, was inversely correlated (P = 0.04) to age at NP. KV, but not MBL, was directly correlated (P = 0.009) to MA. Average MA was 48 +/- 94 mg/24 hr and was correlated to the time from NP (P = 0.026). The remaining kidney increases in volume much more than in length. The increase in KV is related to the degree of MA, whereas the increase in MBL is higher in subjects younger at NP. The high prevalence of significant MA, which is in turn related to the time from NP and to the KV, raises some concerns about the long-term renal prognosis of children NP for WT.