Abstract 4693

Loss of Structural Maintenance of Chromosomes 1A Protein Expression is Associated with a Poor Prognosis in Acute Myeloid Leukemia

Utz Krug, Claudia Hömme, Nicola Tidow, Horst Bürger, Gabriele Köhler, Achim Heinecke, Thomas Büchner, Wolfgang E. Berdel, Steffen Koschmieder, Carsten Müller-Tidow

Introduction

Acute myelogenous leukemia is a genetically heterogenous disease with many risk factors for a poor prognosis. One of the most important independent risk factor in AML is the age at diagnosis. Older patients with AML generally have a poor prognosis which suggests that the biology of AML in elderly patients differs from AML in younger patients.

Methods

Gene expression profiling was carried out to identify age related changes in AML blasts of 67 AML patients of different age (range: 17 to 80 years). Among the genes that correlated with age, SMC1A was selected for protein expression studies. A tissue array was created containing bone marrow histology samples of 135 patients with newly diagnosed AML of different ages and probed with an antibody against SMC1A and protein expression was quantified by the DAKO score.

Results

131 genes showed a significant correlation between mRNA expression levels and patient age. Increasing age was associated with significantly decreased mRNA levels of SMC1A. 116 patient samples were evaluable for SMC1A protein expression and expression of SMC1A protein was low or absent in 74 out of 116 AML specimens. SMC1A protein expression did not show a correlation with patients' age at diagnosis. Both event free survival (2.6 months vs. 10.3 months, p=0.003, see figure) and overall survival (10.4 months vs. 22.6 months, p=0.015, see figure) were significantly worse in patients with low or absent SMC1A protein expression. In a multivariate analysis, SMC1A protein expression level remained a significant prognostic factor for event free survival (p=0.014) with a borderline significance for overall survival (p=0.066).

Conclusions

We identified 131 genes with putative age-dependent microarray mRNA expression and identified low levels of SMC1A protein expression as a marker for poor prognosis in patients with newly diagnosed acute myeloid leukemia.

graphic
View largeDownload slide
Disclosures:

No relevant conflicts of interest to declare.

Topics:
chromosomes, leukemia, myelocytic, acute, rna, messenger, antibodies, gene expression profiling, prognostic factors, tissue microarray, older adult, blast cells, bone marrow

This icon denotes an abstract that is clinically relevant.

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2009 by The American Society of Hematology
2009
Sign in via your Institution