Clinical impact of CD200 expression in patients with acute myeloid leukemia and correlation with other molecular prognostic factors

Daniela Damiani, Mario Tiribelli, Donatella Raspadori, Santina Sirianni, Alessia Meneghel, Margherita Cavalllin, Angela Michelutti, Eleonora Toffoletti, Antonella Geromin, Erica Simeone, Monica Bocchia, Renato Fanin, Daniela Damiani, Mario Tiribelli, Donatella Raspadori, Santina Sirianni, Alessia Meneghel, Margherita Cavalllin, Angela Michelutti, Eleonora Toffoletti, Antonella Geromin, Erica Simeone, Monica Bocchia, Renato Fanin

Abstract

CD200, a protein belonging to the immunoglobulin superfamily, has been associated with a poor prognosis in lymphoproliferative disorders and in acute leukemia. We studied the expression of CD200 in a series of 244 patients with diagnosis of acute myeloid leukemia (AML), to evaluate its impact on outcome and its possible association with other known prognostic factors. CD200 was found in 136/244 (56%) patients, in 41 of whom (30%) with high intensity of expression (MFI ≥ 11). CD200 was more frequent in secondary compared to de novo leukemia (p = 0.0006), in CD34 positive cases (p = 0.00001), in Bcl2 overexpressing cases (p = 0.01), in those wild-type Flt3 (p = 0.004) and with favorable or unfavorable compared to intermediate karyotype (p = 0.0003). CD200+ patients have a two-fold lower probability to attain complete remission, both in univariate (p = 0.006) and multivariate (p = 0.04) analysis. The negative impact of CD200 was found also in overall survival (p = 0.02) and was correlated with the intensity of expression of the molecule (p = 0.024). CD200 has an additive negative impact on survival in patients with unfavorable cytogenetic (p = 0.046) and in secondary leukemia (p = 0.05), and is associate with a worsening of outcome in patients with favorable biological markers, such as mutated NPM (p = 0.02), wild-type Flt3 (p = 0.034), negativity of CD34 (p = 0.03) and of CD56 (p = 0.03). In conclusion, CD200 is emerging as both a prognostic factor and a potential target of novel therapeutic approaches for AML, aiming to reverse the "do not eat me" signal of CD200 or to manipulate the suppressive immune microenvironment induced by CD200 binding to its receptor.

Keywords: CD200; acute myeloid leukemia; prognosis; survival.

Conflict of interest statement

CONFLICTS OF INTEREST

None.

Figures

Figure 1. Overall survival of the entire…
Figure 1. Overall survival of the entire population according to CD200 expression, p = 0.02, a. and by CD200 intensity of expression, p = 0.024, b. CD200 negative: MFI = 1; CD200 low: MFI < 11; CD200 high: MFI ≥ 11
Figure 2. Overall survival in patients with…
Figure 2. Overall survival in patients with unfavorable cytogenetics: difference in CD200 negative and in CD200 positive patients, p = 0.046, a. and according to CD200 MFI, p = 0.06, b.
Figure 3. Overall survival by CD200 intensity…
Figure 3. Overall survival by CD200 intensity of expression in patients FLT3-ITD negative p = 0.034, a. and in NPM mutated group, p = 0.02, b.
Figure 4. Overall survival according to CD200…
Figure 4. Overall survival according to CD200 MFI in CD56 negative patients, p = 0.04, a. and in CD34 negative patients, p = 0.03, b.
Figure 5. Overall survival by CD200 expression…
Figure 5. Overall survival by CD200 expression in de novo, p = 0.04 a. and secondary leukemia, p = 0.05 b.

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