Leukemic samples characteristics associated with clonogenic growth.

In this study, we attempted to delineate readily assessable characteristics from 100 leukemic samples associated with in-vitro growth. Successful growth defined as production of greater than 30 clusters and/or colonies per culture dish was obtained in 68% of samples. More than 10 colonies were found in 59% and greater than 30 colonies in 51% of cultures, respectively. Leukemic cells from patients previously treated with aggressive cytotoxic chemotherapy grew significantly better than cells from untreated patients, independently of the above definitions of cloning success. Cells from peripheral blood had a weak, albeit significant growth advantage over bone marrow cells (p = 0.032) when cluster growth was taken into account for growth success. When colony growth alone was used as criterium, no growth advantage was found. The morphological subtype and the proliferation kinetics prior to cell plating did not affect cloning success. A high labeling index had predictive value for subsequent growth, but only in bone marrow cells. By multivariate analysis, we found that treatment status was the most important factor correlated with in-vitro growth.

Effects of 13-cis retinoic acid and Ara-C on differentiation and proliferation of non-promyelocytic acute myelogenous leukemia.

An alternative to a cell-kill strategy for eradication of acute myelogenous leukemia, is to restore normal differentiation. Vitamin A derivatives demonstrate differentiation-inducing activity both in vitro and in vivo on promyelocytic leukemic cells. We tested the ability of 13-cis retinoic acid to reduce proliferation and induce differentiation in 10 samples from patients with acute non-promyelocytic leukemia. DNA synthesis and leukemia colony formation were affected to varying degrees by a prolonged exposure to the vitamin A compound. Morphologically and cytochemically no differentiation was determined either after 48 h in suspension cultures or 7 additional days in semi-solid cultures. Alkaline leukocyte phosphatase, a biochemical marker of differentiation, was significantly increased in five samples. DNA synthesis in these samples was significantly reduced as compared to samples failing to express alkaline leukocyte phosphatase following 13-cis retinoic acid treatment. DNA synthesis of these same 5 samples was also strongly inhibited by Ara-C. Expression of alkaline leukocyte phosphatase following 13-cis retinoic acid exposure may be a useful indicator for cells amenable to 13-cis retinoic acid or Ara-C treatment.