Complement cascade gene expression defines novel prognostic subgroups of acute myeloid leukemia

• Complement pathway gene expression is variable across acute myeloid leukemia samples.
• Complement regulator genes are implicated in poor outcome in patients with acute myeloid leukemia.
• A three-gene signature of CFH, CFD, and SERPING1 is a highly prognostic marker.

The involvement of the complement pathway in cancer is supported by a growing body of evidence, and yet its role in acute myeloid leukemia (AML) has not been extensively studied. We examined the expression of 87 genes in the complement, coagulation, and fibrinolysis-proteolytic pathways in 374 cytogenetically normal AML samples and observed that these samples can be divided into subgroups on the basis of complement gene expression. Three complement regulatory genes were linked to poor outcome as individual factors in a multivariate analysis (CFH, CFD, and SERPING1) in multiple cohorts. The combined expression of these genes was significantly associated with poorer overall survival in two cohorts of patients <60 years of age, independent of other factors (p ≤ 0.0004). For patients with an intermediate molecular risk, this three-gene risk marker enabled stratification of patients into prognostic subgroups with survival ranging from 17.4% to 44.1%. Thus, the expression of complement pathway genes is linked to outcome in AML, and a three-gene risk marker may improve the risk assessment of patients.