title: Expression of poliovirus receptor-related proteins PRR1 and PRR2 in acute myeloid leukemia: first report of surface marker analysis, contribution to diagnosis, prognosis and implications for future therapeutical strategies.
abstract: Poliovirus receptor-related (PRR) proteins belong to the Nectin-adhesion molecules' group, are expressed on endothelial cells and on CD34(+) stem cells and mediate the organization of endothelial and epithelial junctions. There is evidence to suggest, that those receptors could have a role in leukemia. We have studied the expression of PRR molecules PRR1 and PRR2 on mononuclear bone marrow (BM) cells of 55 patients with acute myeloid leukemia (AML) at first diagnosis by FACS-analysis using directly Phycoerythrin-labeled markers (PRR1 clone R1.302.12; PRR2 clone R2.477.1) in combination with other Fluorescein conjugated antibodies to evaluate the blast phenotype in AML. The leukemic gate included blasts and residual monocytes and lymphocytes. A case was defined as positive, if more than 20% of the gated cells expressed the regarding receptor. We could demonstrate, that on average 35% PRR1(+) or 45% PRR2(+) cells in AML were found. Within FAB-types we observed a high PRR1 expression in cases with M3 and M4 and lowest expressions in M0 and M5; a high PRR2 expression was found in cases with M3, M4, M5 and M1 and lowest expressions in M0 and M2. Separating our patients' cohorts in cytogenetic risk groups we could detect a significant higher proportion of PRR1(+) cases (73% vs. 25% of cases, P = 0.009) or PRR1(+) cells (57% vs. 18% of cases, P = 0.001) in the cytogenetic favorable risk vs. poor risk group (75% vs. 32% PRR2(+) cases). Moreover cut-off-values with a maximum probability for a significant differentiation between cases with higher or lower levels of these markers could be found: cases with >78% PRR1(+) and cases with >77% PRR2(+) cells were characterized by a tendency for longer relapse free survival times. Qui-square analyses showed, that 3 of 4 cases with FAB-type M3 (P = 0.03) or a favorable karyotype (P = 0.04) were found in the group with >7% PRR1(+) cells, due to only few cases available a similar correlation, however, could not be found in cases with >78% PRR2(+) cells. We can conclude, that blasts in AML regularly express PRR1 and PRR2. Cases with a high expression of PRR1 or PRR2 are characterized by a more favorable prognosis. With respect to the individual PRR-status the benefit of biological response modifiers as priming agents, differentiation mediators or factors influencing cellular metabolisms inducing factors can be discussed under a new point of view.
authors.affiliation: Medical Department 3, Klinikum Grosshadern, University of Munich, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Graf
authors.forename: S
authors.initials: S
authors.lastname: Reif
authors.forename: K
authors.initials: K
authors.lastname: Hecht
authors.forename: T
authors.initials: T
authors.lastname: Kroell
authors.forename: V
authors.initials: V
authors.lastname: Nuessler
authors.forename: H
authors.initials: H
authors.lastname: Schmetzer
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015331:Cohort Studies; D018572:Disease-Free Survival; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D000075983:Nectins; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D000075983:Nectins