Expression of RANK-L and in part of PD-1 on blasts in patients with acute myeloid leukemia correlates with prognosis.
BACKGROUND
Co-stimulatory receptor (COR) and ligand (COL) expression on immune effectors are known to be relevant for immunological interactions and might be of prognostic relevance if expressed on acute myeloid leukemia (AML) blasts as reported for receptors of the tumor necrosis factor receptor family.


OBJECTIVE
Antigen expression profiling of COR (RANK, PD-1), COL (RANK-L, PD-1L), and HLA-ABC-antigens on blasts from 90 AML-patients at first diagnosis was performed by flow cytometry (SFI-Level characterization) and findings were correlated with clinical parameters.


RESULTS
RANK expression was higher in immature compared to mature FAB groups (P = 0.08). As a monocytic marker, we identified HLA-ABC (P = 0.07). Prognostic analysis revealed a higher probability of overall survival in cases with lower RANK-L expression (<1.6 and ≥1.6, 15.6 vs. 12.2 months, P = 0.008, hazard ratio 0.36, P = 0.008). No significant impact of PD-1/L expression for patients'(pts) survival was seen but a correlation of PD-1 with a secondary AML (P = 0.03). Prolonged disease-free survival however correlated with higher PD-1 expression (≥1.1 vs. <1.1, 31.4 vs. 12.7 months; P = 0.03).


CONCLUSIONS
Our study revealed that RANK-L is a promising marker to forecast pts' prognosis in AML. Immune checkpoint receptor PD-1/L as well as RANK and HLA-ABC did not show an impact on pts' survival.
Section of Molecular Cancer Therapeutics, Therapeutic Radiology-Radiation Oncology, University of Minnesota, Masonic Cancer Center, Minneapolis, MN, USA.|Department for Hematology and Oncology, Med Dept II, University Hospital of Tuebingen, Tuebingen, Germany.
Joerg Uwe
JU
Schmohl
Department for Hematology and Oncology, Med Dept II, University Hospital of Tuebingen, Tuebingen, Germany.|Clinical Collaboration Unit Translational Immunology, German Cancer Consortium and German Cancer Research Center, Partner site Tuebingen, Department for Internal Medicine II, Eberhard Karls University Tuebingen, Tuebingen, Germany.
Tina
T
Nuebling
Department for Hematology and Oncology, Med Dept II, University Hospital of Tuebingen, Tuebingen, Germany.|Clinical Collaboration Unit Translational Immunology, German Cancer Consortium and German Cancer Research Center, Partner site Tuebingen, Department for Internal Medicine II, Eberhard Karls University Tuebingen, Tuebingen, Germany.
Julia
J
Wild
Department for Hematopoetic Cell Transplantation, Med. Dept.III, University Hospital of Munich, Munich, Germany.
Tanja
T
Kroell
Department for Hematology and Oncology, Med Dept II, University Hospital of Tuebingen, Tuebingen, Germany.
Lothar
L
Kanz
Department for Hematology and Oncology, Med Dept II, University Hospital of Tuebingen, Tuebingen, Germany.|Clinical Collaboration Unit Translational Immunology, German Cancer Consortium and German Cancer Research Center, Partner site Tuebingen, Department for Internal Medicine II, Eberhard Karls University Tuebingen, Tuebingen, Germany.
Helmut Rainer
HR
Salih
Department for Hematopoetic Cell Transplantation, Med. Dept.III, University Hospital of Munich, Munich, Germany.
Helga
H
Schmetzer
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D020732:Cytogenetic Analysis; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics* / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics* / Q000378:metabolism; D012008:Recurrence; D055815:Young Adult
D015415:Biomarkers; D061026:Programmed Cell Death 1 Receptor; D053245:RANK Ligand
Receptor activator of nuclear factor kappa-B ligand; acute myeloid leukemia; human leukocyte antigen molecule class I; prognosis; programmed death-1; programmed death-1/Ligand