Premature Chromosome Condensation Studies in Human Leukemia. 2. Proliferative Potential Changes After Induction Therapy for AML Patients

Abstract

Twenty-two patients with acute myelogenous leukemia (AML) were studied serially during remission induction therapy using the technique of premature chromosome condensation (PCC). Mononuclear cells from bone marrow aspirations were fused with mitotic Chinese hamster ovary cells, and the PCC were scored for fraction of cells in G1, S, and G2. The proliferative potential index PPI, or fraction of the G1 cells in late G1) and degree of chromosome damage were also determined. These results were compared to the changes in bone marrow morphology and blast counts during therapy and correlated with the clinical outcome. Patients who responded to chemotherapy generally exhibited an initial drop in PPI concommitant with chromosome damage. This was followed by a rise in the PPI and fraction of S-phase cells prior to clinical evidence of bone marrow regeneration. As the bone marrow and blood continued to regenerate to normal levels, the PPI value decreased to intermediate levels (less than 35%). In contrast, patients who did not achieve complete remission were observed to exhibit no detectable PCC changes or continued high PPI values after regeneration. High blast counts in the marrow during the regenerative phase accompanied by low PPI values were correlated with a favorable prognosis, since all patients with such a pattern achieved complete remission in that course or the subsequent course of therapy. The PCC technique, therefore, is useful in monitoring response to remission induction therapy in AML patients and can complement morphological and cytogenetic parameters. This ability might be especially useful during the regenerative period when normal and leukemic regeneration is difficult to distinguish by classical techniques.