Correlation of the microculture-kinetic drug-induced apoptosis assay with patient outcomes in initial treatment of adult acute myelocytic leukemia

Abstract

Overall survival (OS) with acute myeloid leukemia (AML) remains poor. Determining prognostic factors will help in selecting patients for appropriate treatments. Our aim was to determine whether the level of drug-induced apoptosis (chemosensitivity) demonstrated by the microculture-kinetic drug-induced apoptosis (MiCK) assay significantly predicted outcomes after standard AML induction therapy. A total of 109 patients with untreated AML had blood and/or bone marrow aspirate samples analyzed for anthracycline-induced apoptosis using the MiCK assay. The amount of apoptosis observed over 48 h was determined and expressed as kinetic units of apoptosis (KU). Complete remission (CR) was significantly higher (72%) in patients with high idarubicin-induced apoptosis >3 KU compared to patients with apoptosis ≤3 KU (p = 0.01). Multivariate analysis showed the only significant variables to be idarubicin-induced apoptosis and karyotype. Median overall survival of patients with idarubicin-induced apoptosis >3 KU was 16.1 months compared to 4.5 months in patients with apoptosis ≤3 KU (p = 0.004). Multivariate analysis showed the only significant variable to be idarubicin-induced apoptosis. Chemotherapy-induced apoptosis measured by the MiCK assay demonstrated significant correlation with outcomes and appears predictive of complete remission and overall survival for patients receiving standard induction chemotherapy.

Keywords::

• Acute myeloid leukemia
• apoptosis
• MiCK assay
• idarubicin
• cytarabine

Acknowledgements

The authors thank Mark J. Koury, MD and John P. Greer, MD for providing preliminary data from previous studies with leukemia cells of patients with AML.

This research was supported by in part by a Translational Research Grant to Mark J. Koury from the Leukemia and Lymphoma Society and research funding from DiaTech Oncology.

Potential conflict of interest

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