Development of a simple, blood based lymphoproliferation assay to assess the clinical status of patients with acute lymphoblastic leukemia

Abstract

Although childhood acute lymphoblastic leukemia (ALL) is highly responsive to chemotherapy, reliable techniques are needed to determine treatment outcome and predict relapse. Employing a 9-O-acetyl sialic acid binding lectin, ATNH, we have identified two 9-O-acetylated sialogycoconjugates (9-OAcSGs) as novel biomarkers expressed selectively on leukemic blasts of ALL patients. Presently, we report a non-invasive, blood based lymphoproliferation assay, which employs the maximal Iymphoproliferative dose of ATN_H (MLD) to assess the status of 9-OAcSGs with progressive therapy. A low MLD (0.18±0.01µg) in untreated patients reflects increased expression of 9-OAcSGs which decline following therapy (MLD=2.10±0.60 µg), persist during maintenance therapy (MLD=4.50±1.60 µg)/follow-up (MLD=5.50±0.85 µg) and are re-induced with relapse (MLD=0.25±0.01 µg). Since the assay detects lymphoblasts with a sensitivity of 10-4, shows no cross-reactivity with other hematological disorders (n=48) and has been tested in 212 patients, it meets clinical consideration.