Cell Cycle Parameters as Biological Predictors of Prognosis in AML: A Review and Update of Cell Cycle Kinetics and Remission Induction/Duration in Acute Leukemia

Abstract

Although the prognostic and clinical significance of cell cycle kinetic studies in neoplastic diseases has been inconclusive at worst and controversial at best, new advances in techniques to study cell cycle characteristics have dramatically improved our ability to more accurately measure the parameters of labeling index (LI), S-phase time (Ts) and total cell cycle time (Tc), and subsequently to find any correlations which would enable us to use these as prognostic indicators. Data from 285 patients with acute myeloid leukemia (AML) who were given in-vivo infusion of the thymidine analogue bromodeoxyuridine (BrdU) prior to chemotherapy show differences in mean labeling indices derived from bone marrow aspirates versus biopsies-being 9.2% and 22.2% respectively. The Tc and Ts were obtained by double labeling the aspirates with tritiated thymidine in-vitro. In 102 uniformly treated patients with standard risk de novo AML, correlations between cell cycle parameters thus measured and clinical data were sought. Although no relation of cell cycle characteristics to remission-induction outcome was observed, patients with below median biopsy LI and above median Tc showed longer remission durations (p = 0.02 and 0.04). We conclude that patients with slowly cycling leukemias have longer and more durable remissions most probably as a result of retarded regrowth of leukemic myeloblasts between courses of consolidation therapy. KEY WORDS:Acute myeloid leukemia cell cycle remission induction remission duration bromodeoxyuridine iododeoxyuridine

Multiscale Model Identifies Improved Schedule for Treatment of Acute Myeloid Leukemia In Vitro With the Mcl‐1 Inhibitor AZD5991

“…We assumed that Mcl‐1 expression levels in a given cell do not change over time (production and synthesis rates are constant at all times). Because the tumor models used in this work exhibit rapid doubling times in vitro (e.g., the 40 hours we use in this work) and in vivo (clinical doubling AML may be as short as 3 days 39 ), the lack of mechanism to alter expression during the lifetime of a single cell does not seem to us a severe limitation. As a result, founder cells start with a particular protein level at birth.…”