Clinical impact of CD200 expression in patients with acute myeloid leukemia and correlation with other molecular prognostic factors.
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.
Division of Hematology and Bone Marrow Transplantation, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy.
Daniela
D
Damiani
Division of Hematology and Bone Marrow Transplantation, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy.
Mario
M
Tiribelli
Division of Hematology, University of Siena, Siena, Italy.
Donatella
D
Raspadori
Division of Hematology, University of Siena, Siena, Italy.
Santina
S
Sirianni
Division of Hematology and Bone Marrow Transplantation, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy.
Alessia
A
Meneghel
Division of Hematology and Bone Marrow Transplantation, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy.
Margherita
M
Cavalllin
Division of Hematology and Bone Marrow Transplantation, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy.
Angela
A
Michelutti
Division of Hematology and Bone Marrow Transplantation, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy.
Eleonora
E
Toffoletti
Division of Hematology and Bone Marrow Transplantation, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy.
Antonella
A
Geromin
Division of Hematology and Bone Marrow Transplantation, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy.
Erica
E
Simeone
Division of Hematology, University of Siena, Siena, Italy.
Monica
M
Bocchia
Division of Hematology and Bone Marrow Transplantation, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy.
Renato
R
Fanin
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34 / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D019002:CD56 Antigen / Q000032:analysis; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012008:Recurrence; D012074:Remission Induction; D015398:Signal Transduction; D013997:Time Factors; D016896:Treatment Outcome; D019139:Tumor Escape; D059016:Tumor Microenvironment; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
D015703:Antigens, CD; D018952:Antigens, CD34; C000595707:BCL2 protein, human; D014408:Biomarkers, Tumor; D019002:CD56 Antigen; C522918:NCAM1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; C042739:antigens, CD200
CD200; acute myeloid leukemia; prognosis; survival