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. 2016 Sep 20;7(38):62377-62385.
doi: 10.18632/oncotarget.11481.

Tetraspanin CD81 is an adverse prognostic marker in acute myeloid leukemia

Thomas Boyer  1   2 , Soizic Guihard  2 , Christophe Roumier  1 , Pauline Peyrouze  2 , Fanny Gonzales  2 , Céline Berthon  2   3 , Bruno Quesnel  2   3 , Claude Preudhomme  1   2 , Hélène Behal  4 , Alain Duhamel  4 , Catherine Roche-Lestienne  2   5 , Meyling Cheok  2
Affiliations

Tetraspanin CD81 is an adverse prognostic marker in acute myeloid leukemia

Thomas Boyer et al. Oncotarget. .

Abstract

CD81 is a cell surface protein which belongs to the tetraspanin family. While in multiple myeloma its expression on plasma cells is associated with worse prognosis, this has not yet been explored in acute myeloid leukemia (AML). We measured membrane expression of CD81 on AML cells at diagnosis, evaluated its association with AML characteristics and its influence on patient outcome after intensive chemotherapy in a cohort of 134 patients. CD81 was detected in 92/134 (69%) patients. Patients with AML expressing CD81 had elevated leukocyte count (P=0.02) and were more likely classified as intermediate or adverse-risk by cytogenetics (P<0.001). CD81 expression had a negative impact on survival (event-free survival, overall survival and relapse-free survival) in univariate (P<0.001) and in multivariate analyses (P=0.003, 0.002 and <0.001, respectively). CD81 has a negative impact on OS in patients with NPM1 mutation (P=0.01) and in patients ELN-favorable (P=0.002). In conclusion, this cell surface marker may be a new prognostic marker for diagnostic risk classification and a potential therapeutic target for drug development in AML.

Keywords: CD81; acute myeloid leukemia; flow cytometry; prognosis; tetraspanin.

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Conflict of interest statement

The authors declare no conflicts of interest

Figures

Figure 1
Figure 1. CD81 expression on normal and AML blast cells
A. Normal bone marrow sample overlay of mean fluorescence intensity histograms of CD81 on blast cells. Isotype control is colored in black. B. Comparison of CD81 expression on blast cells between normal bone marrow samples (n=11) and diagnostic bone marrow from patients with de novo AML (n=134).
Figure 2
Figure 2. Primary AML have varying CD81 expression on blast cells
Representative examples of mean fluorescence intensity histograms of different types of AML according to CD81 expression: A. Example of high CD81 blast expression (CD81++) B. Example of negative CD81 blast expression (CD81−); C. intermediate CD81 blast expression (CD81+). Isotype control corresponds to the red histogram.
Figure 3
Figure 3. High CD81 expression on blast cells predicts poor outcome in AML
Survival curves of A. OS, B. EFS, C. RFS stratified by CD81 expression measured in diagnostic bone marrow of AML patients. Shown is the survival of patients with AML either CD81− in green (less than 20%), CD81+ in black (20 to 50%), or CD81++ in red (greater than 50%). Numbers at risk at each year of follow-up are given. P-values based on logrank test.
Figure 4
Figure 4. Effect of CD81 expression on Overall Survival in favorable-risk patients
Curve shown in black illustrates overall survival of patients with CD81− AML (less than 20%), CD81+ in red (greater than 20%) for A. NPM1 mutated patients and B. ELN-favorable risk group. Numbers at risk at each year of follow-up are given. P-values based on logrank test.
See this image and copyright information in PMC

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