Urinary excretion of proteolyzed alpha1-antitrypsin: specificity, quantitation, and relation to therapy response in...

During remission induction chemotherapy, a 41-kDa cleavage product of alpha1-antitrypsin (alpha1-AT41) can be found in the urine of patients with acute myeloid leukemia. By using immunoblotting with antibodies against this protein, 27 patients with acute myeloid leukemia were screened for the excretion of this fragment and the amount of alpha1-AT41 compared with treatment response assessed by therapy-induced cytoreduction in the bone marrow and time to reach remission. Patients with acute lymphoblastic leukemia, malignant lymphomas, and solid tumors receiving chemotherapy, patients with nonmalignant diseases like sepsis and kidney dysfunction, and healthy subjects were probed to evaluate the specificity of this phenomenon. In 74% of the acute myeloid leukemia patients, the truncated inhibitor was detected. Mean concentration of peak excretion was found to be 6.7 microgram/mg creatinine (range, 1.1-41 microgram/mg). Among the patients treated with induction chemotherapy, those who responded completely (<5% residual marrow blast cells) exhibited significantly higher alpha1-AT41 concentrations than the nonresponders (P < 0.03). Patients who showed a partial response (6-25% residual blasts) excreted intermediate values of the protein. The probability of median time to reach remission was 40 days in patients excreting the truncated inhibitor in measurable amounts compared to 100 days in patients negative for alpha1-AT41 (P < 0.02). The 41-kDa fragment was also found in one of 10 patients with acute lymphoblastic leukemia and in 3 of 18 lymphoma patients but not in those with solid tumors, infections, or kidney disease or in healthy individuals.