High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study - PubMed (original) (raw)

Clinical Trial

. 2008 Jun 1;111(11):5371-9.

doi: 10.1182/blood-2007-11-124958. Epub 2008 Mar 31.

Michael D Radmacher, Amy S Ruppert, Susan P Whitman, Peter Paschka, Krzysztof Mrózek, Claudia D Baldus, Tamara Vukosavljevic, Chang-Gong Liu, Mary E Ross, Bayard L Powell, Albert de la Chapelle, Jonathan E Kolitz, Richard A Larson, Guido Marcucci, Clara D Bloomfield; Cancer and Leukemia Group B (CALGB)

Collaborators, Affiliations

Clinical Trial

High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study

Christian Langer et al. Blood. 2008.

Abstract

BAALC expression is considered an independent prognostic factor in cytogenetically normal acute myeloid leukemia (CN-AML), but has yet to be investigated together with multiple other established prognostic molecular markers in CN-AML. We analyzed BAALC expression in 172 primary CN-AML patients younger than 60 years of age, treated similarly on CALGB protocols. High BAALC expression was associated with FLT3-ITD (P = .04), wild-type NPM1 (P < .001), mutated CEBPA (P = .003), MLL-PTD (P = .009), absent FLT3-TKD (P = .005), and high ERG expression (P = .05). In multivariable analysis, high BAALC expression independently predicted lower complete remission rates (P = .04) when adjusting for ERG expression and age, and shorter survival (P = .04) when adjusting for FLT3-ITD, NPM1, CEBPA, and white blood cell count. A gene-expression signature of 312 probe sets differentiating high from low BAALC expressers was identified. High BAALC expression was associated with overexpression of genes involved in drug resistance (MDR1) and stem cell markers (CD133, CD34, KIT). Global microRNA-expression analysis did not reveal significant differences between BAALC expression groups. However, an analysis of microRNAs that putatively target BAALC revealed a potentially interesting inverse association between expression of miR-148a and BAALC. We conclude that high BAALC expression is an independent adverse prognostic factor and is associated with a specific gene-expression profile.

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Figures

Figure 1

Figure 1

Outcome of cytogenetically normal AML patients according to BAALC expression levels. (A) Disease-free survival. (B) Overall survival.

Figure 2

Figure 2

Heat map of the BAALC signature. Columns represent samples and rows represent genes ordered by hierarchical cluster analysis using average linkage and one minus Pearson correlation as the distance metric. Shading indicates relative expression of each gene with respect to the gene's median expression (black equal to, red above, and blue below the median value).

References

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