Detection of aberrant transcription of major histocompatibility complex class II antigen presentation genes in chronic lymphocytic leukaemia identifies HLA-DOA mRNA as a prognostic factor for survival

Y Souwer, M.E.D. Chamuleau, A.A. van de Loosdrecht, E. Tolosa, T. Jorritsma, J.J.F. Muris, M.N.M. van Poppel, S.N. Snel, L. van de Corput, G.J. Ossenkoppele, C.J.L.M. Meijer, J.J. Neefjes, S.M. van Ham

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

In human B cells, effective major histocompatibility complex (MHC) class II-antigen presentation depends not only on MHC class II, but also on the invariant chain (CD74 or Ii), HLA-DM (DM) and HLA-DO (DO), the chaperones regulating the antigen loading process of MHC class II molecules. We analysed immediate ex vivo expression of HLA-DR (DR), CD74, DM and DO in B cell chronic lymphocytic leukaemia (B-CLL). Real-time reverse transcription polymerase chain reaction demonstrated a highly significant upregulation of DRA, CD74, DMB, DOA and DOB mRNA in purified malignant cells compared to B cells from healthy donors. The increased mRNA levels were not translated into enhanced protein levels but could reflect aberrant transcriptional regulation. Indeed, upregulation of DRA, DMB, DOA and DOB mRNA correlated with enhanced expression of class II transactivator (CIITA). In-depth analysis of the various CIITA transcripts demonstrated a significant increased activity of the interferon-gamma-inducible promoter CIITA-PIV in B-CLL. Comparison of the aberrant mRNA levels with clinical outcome identified DOA mRNA as a prognostic indicator for survival. Multivariate analysis revealed that the prognostic value of DOA mRNA was independent of the mutational status of the IGHV genes. Thus, aberrant transcription of DOA forms a novel and additional prognostic indicator for survival in B-CLL
Original languageUndefined/Unknown
Pages (from-to)334-343
JournalBritish Journal of Haematology
Volume145
Issue number3
DOIs
Publication statusPublished - 2009

Cite this

@article{b728f4b93d344961879e109e5dcac128,
title = "Detection of aberrant transcription of major histocompatibility complex class II antigen presentation genes in chronic lymphocytic leukaemia identifies HLA-DOA mRNA as a prognostic factor for survival",
abstract = "In human B cells, effective major histocompatibility complex (MHC) class II-antigen presentation depends not only on MHC class II, but also on the invariant chain (CD74 or Ii), HLA-DM (DM) and HLA-DO (DO), the chaperones regulating the antigen loading process of MHC class II molecules. We analysed immediate ex vivo expression of HLA-DR (DR), CD74, DM and DO in B cell chronic lymphocytic leukaemia (B-CLL). Real-time reverse transcription polymerase chain reaction demonstrated a highly significant upregulation of DRA, CD74, DMB, DOA and DOB mRNA in purified malignant cells compared to B cells from healthy donors. The increased mRNA levels were not translated into enhanced protein levels but could reflect aberrant transcriptional regulation. Indeed, upregulation of DRA, DMB, DOA and DOB mRNA correlated with enhanced expression of class II transactivator (CIITA). In-depth analysis of the various CIITA transcripts demonstrated a significant increased activity of the interferon-gamma-inducible promoter CIITA-PIV in B-CLL. Comparison of the aberrant mRNA levels with clinical outcome identified DOA mRNA as a prognostic indicator for survival. Multivariate analysis revealed that the prognostic value of DOA mRNA was independent of the mutational status of the IGHV genes. Thus, aberrant transcription of DOA forms a novel and additional prognostic indicator for survival in B-CLL",
author = "Y Souwer and M.E.D. Chamuleau and {van de Loosdrecht}, A.A. and E. Tolosa and T. Jorritsma and J.J.F. Muris and {van Poppel}, M.N.M. and S.N. Snel and {van de Corput}, L. and G.J. Ossenkoppele and C.J.L.M. Meijer and J.J. Neefjes and {van Ham}, S.M.",
year = "2009",
doi = "10.1111/j.1365-2141.2009.07625.x",
language = "Undefined/Unknown",
volume = "145",
pages = "334--343",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "3",

}

Detection of aberrant transcription of major histocompatibility complex class II antigen presentation genes in chronic lymphocytic leukaemia identifies HLA-DOA mRNA as a prognostic factor for survival. / Souwer, Y; Chamuleau, M.E.D.; van de Loosdrecht, A.A.; Tolosa, E.; Jorritsma, T.; Muris, J.J.F.; van Poppel, M.N.M.; Snel, S.N.; van de Corput, L.; Ossenkoppele, G.J.; Meijer, C.J.L.M.; Neefjes, J.J.; van Ham, S.M.

In: British Journal of Haematology, Vol. 145, No. 3, 2009, p. 334-343.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Detection of aberrant transcription of major histocompatibility complex class II antigen presentation genes in chronic lymphocytic leukaemia identifies HLA-DOA mRNA as a prognostic factor for survival

AU - Souwer, Y

AU - Chamuleau, M.E.D.

AU - van de Loosdrecht, A.A.

AU - Tolosa, E.

AU - Jorritsma, T.

AU - Muris, J.J.F.

AU - van Poppel, M.N.M.

AU - Snel, S.N.

AU - van de Corput, L.

AU - Ossenkoppele, G.J.

AU - Meijer, C.J.L.M.

AU - Neefjes, J.J.

AU - van Ham, S.M.

PY - 2009

Y1 - 2009

N2 - In human B cells, effective major histocompatibility complex (MHC) class II-antigen presentation depends not only on MHC class II, but also on the invariant chain (CD74 or Ii), HLA-DM (DM) and HLA-DO (DO), the chaperones regulating the antigen loading process of MHC class II molecules. We analysed immediate ex vivo expression of HLA-DR (DR), CD74, DM and DO in B cell chronic lymphocytic leukaemia (B-CLL). Real-time reverse transcription polymerase chain reaction demonstrated a highly significant upregulation of DRA, CD74, DMB, DOA and DOB mRNA in purified malignant cells compared to B cells from healthy donors. The increased mRNA levels were not translated into enhanced protein levels but could reflect aberrant transcriptional regulation. Indeed, upregulation of DRA, DMB, DOA and DOB mRNA correlated with enhanced expression of class II transactivator (CIITA). In-depth analysis of the various CIITA transcripts demonstrated a significant increased activity of the interferon-gamma-inducible promoter CIITA-PIV in B-CLL. Comparison of the aberrant mRNA levels with clinical outcome identified DOA mRNA as a prognostic indicator for survival. Multivariate analysis revealed that the prognostic value of DOA mRNA was independent of the mutational status of the IGHV genes. Thus, aberrant transcription of DOA forms a novel and additional prognostic indicator for survival in B-CLL

AB - In human B cells, effective major histocompatibility complex (MHC) class II-antigen presentation depends not only on MHC class II, but also on the invariant chain (CD74 or Ii), HLA-DM (DM) and HLA-DO (DO), the chaperones regulating the antigen loading process of MHC class II molecules. We analysed immediate ex vivo expression of HLA-DR (DR), CD74, DM and DO in B cell chronic lymphocytic leukaemia (B-CLL). Real-time reverse transcription polymerase chain reaction demonstrated a highly significant upregulation of DRA, CD74, DMB, DOA and DOB mRNA in purified malignant cells compared to B cells from healthy donors. The increased mRNA levels were not translated into enhanced protein levels but could reflect aberrant transcriptional regulation. Indeed, upregulation of DRA, DMB, DOA and DOB mRNA correlated with enhanced expression of class II transactivator (CIITA). In-depth analysis of the various CIITA transcripts demonstrated a significant increased activity of the interferon-gamma-inducible promoter CIITA-PIV in B-CLL. Comparison of the aberrant mRNA levels with clinical outcome identified DOA mRNA as a prognostic indicator for survival. Multivariate analysis revealed that the prognostic value of DOA mRNA was independent of the mutational status of the IGHV genes. Thus, aberrant transcription of DOA forms a novel and additional prognostic indicator for survival in B-CLL

U2 - 10.1111/j.1365-2141.2009.07625.x

DO - 10.1111/j.1365-2141.2009.07625.x

M3 - Article

VL - 145

SP - 334

EP - 343

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 3

ER -