TY - JOUR
T1 - The impact of interferon-alpha2 on HLA genes in patients with polycythemia vera and related neoplasms
AU - Skov, Vibe
AU - Riley, Caroline Hasselbalch
AU - Thomassen, Mads
AU - Kjær, Lasse
AU - Stauffer Larsen, Thomas
AU - Bjerrum, Ole Weis
AU - Kruse, Torben A
AU - Hasselbalch, Hans Carl
PY - 2017/8
Y1 - 2017/8
N2 - Gene expression profiling in Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have unraveled significant deregulation of several immune and inflammation genes of potential importance for clonal evolution. Other mechanisms might be downregulation of major histocompatibility class I and II genes used by tumor cells to escape antitumor T-cell-mediated immune responses. Several genes encoding human leukocyte antigen (HLA) class I and II molecules have been shown to be significantly downregulated. Upregulation of HLA genes is considered one of the mechanisms of action of interferon (IFN)-alpha2, but regulation of these genes during IFN-alpha2 treatment in MPNs has never been studied. Our findings show a significant upregulation of several HLA genes of importance for tumor immune surveillance by IFN-alpha2 treatment in MPNs. This mechanism might enhance the cytotoxic potential of immune cells against MPNs and explain the induction of minimal residual disease by IFN-alpha2 treatment in these patients.
AB - Gene expression profiling in Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have unraveled significant deregulation of several immune and inflammation genes of potential importance for clonal evolution. Other mechanisms might be downregulation of major histocompatibility class I and II genes used by tumor cells to escape antitumor T-cell-mediated immune responses. Several genes encoding human leukocyte antigen (HLA) class I and II molecules have been shown to be significantly downregulated. Upregulation of HLA genes is considered one of the mechanisms of action of interferon (IFN)-alpha2, but regulation of these genes during IFN-alpha2 treatment in MPNs has never been studied. Our findings show a significant upregulation of several HLA genes of importance for tumor immune surveillance by IFN-alpha2 treatment in MPNs. This mechanism might enhance the cytotoxic potential of immune cells against MPNs and explain the induction of minimal residual disease by IFN-alpha2 treatment in these patients.
KW - HLA genes
KW - Interferon-alpha2
KW - myeloproliferative neoplasms
KW - tumor immune surveillance
KW - whole blood transcriptional profiling
KW - Interferon-alpha/pharmacology
KW - Humans
KW - Polycythemia Vera/drug therapy
KW - Gene Expression Profiling
KW - HLA Antigens/genetics
KW - Primary Myelofibrosis/drug therapy
KW - Thrombocythemia, Essential/drug therapy
KW - Myeloproliferative Disorders/drug therapy
KW - Alleles
KW - Gene Expression Regulation/drug effects
U2 - 10.1080/10428194.2016.1262032
DO - 10.1080/10428194.2016.1262032
M3 - Journal article
C2 - 27911124
VL - 58
SP - 1914
EP - 1921
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
SN - 1042-8194
IS - 8
ER -