Class II-associated invariant chain peptide expression on myeloid leukemic blasts predicts poor clinical outcome

Martine E.D. Chamuleau*, Yuri Souwer, S. Marieke Van Ham, Adri Zevenbergen, Theresia M. Westers, Johannes Berkhof, Chris J.L.M. Meijer, Arjan A. Van De Loosdrecht, Gert J. Ossenkoppele

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Effective antitumor responses need the activation of CD4+ T cells. MHC class II antigen presentation requires the release of class II-associated invariant chain peptide (CLIP) from the antigen-binding site. In antigen-presenting cells, human leukocyte antigen DM (HLA-DM; abbreviated DM in this article) catalyzes CLIP dissociation. In B cells, HLA-DO (DO) down-modulates DM function. Cell surface CLIP:HLA-DR (DR) ratio correlates to DO:DM ratio and the efficacy of antigen presentation. We examined III blood and bone marrow samples of patients with newly diagnosed acute myeloid leukemia (AML) for the expression of CLIP, DR, DM, and DO by flow cytometry. Patients with DR+/CLIP- blasts had a significant longer disease-free survival than patients with DR+/CLIP+ blasts. DO, until now believed to be restricted to lymphoid cells, could be demonstrated at protein level as well as by reverse transcription-PCR. DO:DM ratio correlated to CLIP:DR ratio, suggesting that, unlike in other antigen-presenting cells of the nonlymphoid cell type, both DO and DM mediate regulation of CLIP expression in AML blasts. We hypothesize that DR+/CLIP- AML blasts are able to present leukemia-specific antigens to CD4+ T helper cells initiating an effective and long-lasting antitumor response resulting in a prolonged disease-free survival.

Original languageEnglish
Pages (from-to)5546-5550
Number of pages5
JournalCancer Research
Volume64
Issue number16
DOIs
Publication statusPublished - 15 Aug 2004

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