Loss or downregulation of HLA class I expression at the allelic level in acute leukemia is infrequent but functionally relevant, and can be restored by interferon.
Human leukocyte antigen (HLA) class I expression at the allelic level was analyzed in 397 acute myeloid leukemia (AML) and 186 acute lymphoid leukemia (ALL) using a complement-dependent cytotoxicity assay. Impaired recognition possibly due to HLA downregulation was observed in 2% of the patients with AML and ALL in complete remission, and in 8%-15% in the groups with blasts. In 15 instances of diminished cytotoxicity, leukemic cells and control PHA blasts from the same patients were further analyzed using flow cytometry. In 4/6 ALL and 4/9 AML patients HLA downregulation or complete loss (2 patients) of cell surface expression could be confirmed. No genomic abnormalities were observed. In addition, 12 AML and 13 ALL patients were tested during relapse using flow cytometry. In 1/12 AML patients and 1/13 ALL patients allelic downregulation of cell surface expression was found. In two patients tested, downregulation or loss of cell surface expression of HLA class I antigens corresponded with impaired T cell mediated lysis by HLA restricted cytotoxic T lymphocyte.Treatment of the cells with alpha- or gamma-interferon could restore HLA class I expression and T-cell recognition. In conclusion, downregulation of cell surface expression of HLA class I expression at the allelic level in AML and ALL is infrequent but functionally relevant. HLA downregulation was reversible and T-cell recognition could be restored by alpha- or gamma-interferon.
Brouwer
Rolf E
RE
Laboratory of Experimental Hematology, Department of Hematology, Leiden, The Netherlands.
van der Heiden
Pim
P
Schreuder
Geziena M T
GM
Mulder
Arend
A
Datema
Gert
G
Anholts
Jacqy D H
JD
Willemze
Roel
R
Claas
Frans H J
FH
Falkenburg
J H Frederik
JH
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D004252:DNA Mutational Analysis; D015536:Down-Regulation; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006680:HLA Antigens / Q000378:metabolism*; D015234:HLA-A Antigens / Q000378:metabolism; D015235:HLA-B Antigens / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics / Q000494:pharmacology; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D016898:Interferon-alpha; D007371:Interferon-gamma