HLA class I antigen cell surface expression is preserved on acute myeloid leukemia blasts at diagnosis and at relapse

Wetzler, Meir; Baer,; Sj, Stewart; Donohue, Kathleen; Ford, Laurie; Cc, Stewart; Repasky, E A; Ferrone, Soldano

doi:10.1038/sj.leu.2401982

Cited by 54 publications

(35 citation statements)

References 18 publications

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“…In these cases, the selective pressure on APM components could be because of induction and consolidation chemotherapy. Studies by Wetzler et al 20 showed that general MHC class I downregulation on AML blasts could not be detected in patients from ID to relapse, confirming our data on persistent high expression of MHC class I HC from ID to relapse in all four patients evaluated ( Figure 5b). However, from our studies presented here, we conclude that the pattern of peptides presented on the MHC class I of AML blasts can change in disease progression and can, therefore, promote escape from the immune system.…”

Section: Apm Expression In Aml Progressionsupporting

confidence: 91%

“…These antibodies have been used in previous studies of APM component expression in various tissues, 19,20 and were kindly provided by Dr S Ferrone (Roswell Park Memorial Institute, Buffalo, NY, USA). Staining for the different APM components was performed using standard immunohistochemical staining procedures with heat-induced antigen retrieval, and visualization of staining was performed using the avidin-biotin peroxidase method with diaminobenzidine chromatogen (LMP2, LMP7, MHC class I HC) or En-Vision (TAP1, TAP2, b2m; DakoCytomation, Glostrup, Denmark).…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…These showed the expected high to very high expression of all APM components depending on their level of maturation (Supplementary Figure 1). 20 We next evaluated the APM profile of different tumour cell lines, such as KG1a (AML), U937 (lymphoma cells with monocytic characteristic) and K562 (chronic myeloid leukaemia in blast crisis). K562 is a highly de-differentiated cell line that lacks MHC class I expression on the surface.…”

Section: Control-tma For Evaluation Of the Anti-apm Antibodiesmentioning

confidence: 99%

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In situ analysis of the antigen-processing machinery in acute myeloid leukaemic blasts by tissue microarray

et al. 2009

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Section: Apm Expression In Aml Progressionsupporting

confidence: 91%

Section: Immunohistochemistrymentioning

confidence: 99%

Section: Control-tma For Evaluation Of the Anti-apm Antibodiesmentioning

confidence: 99%

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In situ analysis of the antigen-processing machinery in acute myeloid leukaemic blasts by tissue microarray

et al. 2009

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“…We have previously demonstrated that HLA Class I antigen expression is preserved on the surface of AML blasts. 58 HLA Class I molecules bind antigenic peptides and present them to cytotoxic (CD8+) T cells. The recognition of these peptides by cytotoxic T cells triggers a series of events that may result in lysis of target cells.…”

Section: Discussionmentioning

confidence: 99%

HLA-DR antigen-negative acute myeloid leukemia

Wetzler

McElwain

Stewart³

et al. 2003

Leukemia

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Human leukocyte antigen (HLA) Class II antigens are variably expressed on acute myeloid leukemia (AML) blasts. The biological and clinical significance of HLA Class II antigen expression by AML cells is not known. Therefore, we sought to characterize cases of AML without detectable HLA-DR expression. Samples from 248 consecutive adult AML patients were immunophenotyped by multiparameter flow cytometry at diagnosis. HLA-DR antigens were not detected on AML cells from 43 patients, including 20 with acute promyelocytic leukemia (APL), and 23 with other subtypes of AML. All APL cases had t(15;17), but there were no characteristic chromosome abnormalities in non-APL cases. No direct expression of other antigens was identified in HLA-DR-negative APL and non-APL cases. Interestingly, cells from three HLA-DR-negative non-APL patients had similar morphology to that of the hypogranular variant of APL. This morphology, however, was not present in any HLA-DR-positive AML cases. Treatment response was similar in the 23 HLA-DR-negative non-APL and the 205 HLA-DR-positive patients. Finally, relapse was infrequently associated with changes in HLA-DR antigen expression, as the HLA-DR antigen was lost at relapse in only 4% of HLA-DR-positive cases, and was gained at relapse in only 17% of HLA-DR-negative cases. We conclude that HLA-DR-negative AML includes approximately equal numbers of APL and non-APL cases, and that the morphology of HLA-DR-negative non-APL cases can mimic the hypogranular variant of APL. The diagnosis of APL cannot be based on morphology and lack of HLA-DR antigen expression; rather, it requires cytogenetic or molecular confirmation.

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“…In a study on 25 acute myeloid leukemia (AML) patients at diagnosis, HLA class I expression was found to be preserved in all cases. 3 The potential of adoptive T-cell immunotherapy by donorlymphocyte infusions for treating leukemic patients has stimulated interest in HLA class I expression on leukemic cells that could impact on the efficacy of donor-lymphocyte infusions. An HLA and microsatellite genotyping analysis of 44 samples of freshly isolated leukemic blasts did not reveal any case of haplotype loss, although a downregulation of HLA class I expression was observed in 9.1% of the patients samples.…”

Section: Introductionmentioning

confidence: 99%

Pretransplant HLA mistyping in diagnostic samples of acute myeloid leukemia patients due to acquired uniparental disomy

Dubois¹,

Sloan‐Béna

Cesbron

et al. 2012

Leukemia

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Although acquired uniparental disomy (aUPD) has been reported in relapse acute myeloid leukemia (AML), pretransplant aUPD involving chromosome 6 is poorly documented. Such events could be of interest because loss of heterozygosity (LOH) resulting from aUPD in leukemic cells may lead to erroneous results if HLA typing for hematopoietic stem cell donor searches is performed on blood samples drawn during blastic crisis. We report here six AML patients whose HLA typing was performed on DNA extracted from peripheral blood obtained at diagnosis. We observed LOH involving the entire HLA region (three patients), HLA-A, B, C (two patients) and HLA-A only (one patient). An array-comparative genomic hybridization showed that copy number was neutral for all loci, thus revealing partial aUPD of chromosome 6p21. When HLA typing was performed on remission blood samples both haplotypes were detected. A 3 --4% LOH incidence was estimated in AML patients with high blast counts. Based on DNA mixing experiments, we determined by PCR sequence-specific oligonucleotide hybridization on microbeads arrays a detection threshold for HLA-A, B, DRB1 heterozygosity in blood samples with o80% blasts. Because aUPD may be partial, any homozygous HLA result should be confirmed by a second typing performed on buccal swabs or on blood samples from the patient in remission.

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HLA class I antigen cell surface expression is preserved on acute myeloid leukemia blasts at diagnosis and at relapse

Cited by 54 publications

References 18 publications

In situ analysis of the antigen-processing machinery in acute myeloid leukaemic blasts by tissue microarray

In situ analysis of the antigen-processing machinery in acute myeloid leukaemic blasts by tissue microarray

HLA-DR antigen-negative acute myeloid leukemia

Pretransplant HLA mistyping in diagnostic samples of acute myeloid leukemia patients due to acquired uniparental disomy

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