General AML

Overexpression of CD200 is associated with poor prognosis in AML patients – an Italian study

CD200, a membrane protein of the immunoglobulin superfamily, has been shown to lead to poor outcomes in Acute Myeloid Leukemia (AML) patients.1 However, the impact of CD200 expression in Cytogenetically Normal AML (CN-AML) patients and molecularly defined CN-AML subgroups is not yet elucidated, hence the rationale for this study.

In an article published ahead of print in Leukemia Research, Mario Tiribelli from the Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy, and colleagues retrospectively investigated the correlation between CD200 expression and therapy response in CN-AML patients.

In total, 139 treated CN-AML patients (median age = 60 years) were enrolled in this study.

The key results of the study were:
  • Of all patients, 48% (67/139) expressed CD200; high expression observed in 27% (18/67)
  • Complete Remission (CR) in CD200- and CD200+ patients; 79% (56/71) vs 63% (42/67), Odds Ratio (OR) = 0.45, P = 0.03
  • CR in patients with high intensity of CD200; 50% (9/18)
  • 3-year Disease Free Survival (DFS) in patients with high and low expression of CD200 and CD200-; 0% vs 65% vs 68%, respectively, P = 0.019
  • 3-year Overall Survival (OS) CD200+ and CD200- patients; 27% vs 51%, P = 0.01
  • 3-year OS in patients with high and low expression of CD200; 0% vs 35%, P = 0.001
  • High expression of CD200 defined a group of FLT3-ITD-/NPM1+ patients (n = 37) with poor DFS and OS
  • 3-year DFS in FLT3-ITD-/NPM1+ patients with high expression of CD200 and low expression of CD200 and CD200-; 0% vs 50% vs 88%, respectively, P = 0.01
  • 3-year OS in FLT3-ITD-/NPM1+ patients with high expression of CD200 and low expression of CD200 and CD200-; 0% vs 32% vs 60%, respectively, P = 0.05

In summary, high expression of CD200 is associated with poor outcomes in AML patients. Moreover, overexpression of CD200 in FLT3-/NPM1+ AML patients leads to adverse outcomes in this group of patients.

Abstract

Overexpression of CD200, a trans-membrane protein belonging to the immunoglobulin superfamily, has been associated with poor prognosis in patients with acute myeloid leukemia (AML). As few data are available in the subset of cytogenetically-normal (CN) AML, we retrospectively evaluated the correlations between CD200 expression and response to therapy in a series of 139 adults with CN-AML.

CD200 was expressed in 67/139 (48%) cases; 18 of them (28%) expressed CD200 at high intensity. No differences in CD200 expression rate were observed according to age, WBC count, type of leukemia, FLT3 or NMP1 mutation, and CD56 expression. A higher incidence of CD200 expression was observed in CD34+ cases (P < 0.0001) and in BCL2+ patients (P = 0.04).

Complete remission (CR) was evaluable achieved in 98 patients (70%): 56/71 (79%) in CD200- and 47/67 (63%) in CD200+ patients (P = 0.03), with a lower CR rate in patients with high CD200 intensity (9/18, 50%). CD200 expression had a negative impact on long-term outcome. CD200 expression, per se, did not impact on disease-free survival (DFS), but cases with high CD200 expression had a lower 3-year DFS compared to CD200-negative and low-expressing ones (0% vs 65% vs 68%, P = 0.019). Three-year overall survival (OS) was 51% in CD200- and 27% in CD200+ patients (P = 0.01), with a significant difference among cases with low or high CD200 expression (35% vs 0%, P = 0.001). CD200 high expression defined a group with very poor DFS and OS also among the 37 FLT3-/NPM1+: 3-year DFS and OS were 88% and 60% in CD200-, 50% and 32% in CD200 low and 0% and 0% in CD200 high patients, respectively (P = 0.01 for DFS and P = 0.05 for OS).

Our data suggest a negative impact of CD200 expression in CN-AML, with a further worsening in high-expressing cases, also in the subset of FLT3-/NPM1+ patients.

References
  1. Atfy M. et al. CD200 Suppresses the Natural Killer Cells and Decreased its Activity in Acute Myeloid Leukemia Patients. J Leuk. 2015; 3:190. DOI: 10.4172/2329-6917.1000190.
  2. Tiribelli M. et al., High CD200 expression is associated with poor prognosis in cytogenetically normal acute myeloid leukemia, even in FLT3-ITD-/NPM1+ patients. Leuk Res. 2017 Apr 4. DOI: 10.1016/j.leukres.2017.04.001. [Epub ahead of print].
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