In vitro autonomous proliferation in ANLL: clinical and biological significance

In acute non-lymphoblastic leukemia (ANLL) progenitor cells frequently display a certain degree of autonomous growth. The aim of the present work was to analyze the autonomous proliferative capacity of leukemic progenitors in both de novo and secondary to myeloproliferative disorders (MPD) and myelodysplastic syndromes (MDS), acute myeloid leukemias and to correlate with clinical and biological characteristics of the disease. Clonogenic assays with and without leukocyte conditioned medium with PHA (LCM-PHA) were performed and the autonomous proliferation index (API) calculated in a series of 50 patients (34 de novo ANLL, eight secondary to MPD and eight secondary to MDS). Patients were divided into two groups according to their API, low (< or = 0.4) or high (> 0.4). Autonomous growth was observed in 84% of cases studied (82% in de novo ANLL, 75% secondary to MDS and 100% secondary to MPD). The group with the highest API (29 patients) had increased levels of hemoglobin (P = 0.006) and platelets (P = 0.01). A high API was also associated with an immature phenotype of blast cells (P = 0.02). Upon analyzing the de novo ANLL separately we observed that a high API correlated with high Hb values (P = 0.02), a lower rate of complete remission (42% vs 61%) and a lower survival rate (medium of 3 vs 10 months). These findings suggest that the capacity for autonomous proliferation can condition the clinical and biological profile of the disease.