Dysregulation of apoptosis in Waldenstrom's macroglobulinemia does not involve nuclear factor kappa B activation.
Indolent lymphoproliferative disorders such as Waldenstrom's macroglobulinemia (WM) are characterized by defective apoptosis, which leads to progressive accumulation of slowly dividing neoplastic lymphocytes. Activation of nuclear factor kappa B (NFkappaB) is considered to have a central pathogenic role in some hematological malignancies, including multiple myeloma, Hodgkin's disease, and extranodal marginal zone lymphoma (ENMZL). NFkappaB activation may inhibit apoptosis through the transactivation of genes such as Bcl-2 and may therefore be an important mechanism in indolent lymphoproliferative disorders, including WM. In order to assess this potential mechanism, we used immunohistochemistry to determine the presence and subcellular localisation of the major NFkappaB subunits p50 and p65. Nuclear staining of NFkappaB subunits (indicative of activation) was not seen in any of the 40 cases examined. Thirty-seven (95%) cases showed cytoplasmic positivity for both p50 and p65 and one case demonstrated cytoplasmic staining for p65 alone, while the two remaining cases showed complete absence of staining. We would therefore conclude that NFkappaB activation is not a feature of WM and that alternative mechanisms of apoptosis inhibition should be investigated in this disorder.
Leitch
Derek
D
HMDS Laboratory, The General Infirmary at Leeds, Leeds, UK.
Barrans
Sharon L
SL
Jack
Andrew S
AS
Owen
Roger G
RG
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D017209:Apoptosis; D000074018:B-Cell CLL-Lymphoma 10 Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D009363:Neoplasm Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051996:Transcription Factor RelA; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051996:Transcription Factor RelA