Rare lymphoid neoplasms coexpressing B- and T-cell antigens. The role of PAX-5 gene methylation in their pathogenesis.
Title | Rare lymphoid neoplasms coexpressing B- and T-cell antigens. The role of PAX-5 gene methylation in their pathogenesis. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Lazzi, S., Bellan C., Onnis A., De Falco G., Sayed S., Kostopoulos I., Onorati M., D'Amuri A., Santopietro R., Vindigni C., Fabbri A., Righi S., Pileri S., Tosi P., & Leoncini L. |
Journal | Hum Pathol |
Volume | 40 |
Issue | 9 |
Pagination | 1252-61 |
Date Published | 2009 Sep |
ISSN | 1532-8392 |
Keywords | Aged, Antigens, B-Cell-Specific Activator Protein, B-Lymphocytes, Biological Markers, DNA Methylation, Fatal Outcome, Female, Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor, Humans, Immunoglobulin Light Chains, Immunohistochemistry, Immunophenotyping, Killer Cells, Natural, Lymphoma, Male, Middle Aged |
Abstract | We report 3 cases of lymphoid neoplasms with mixed lineage features of T-, NK-, or B-cell marker expression and clonal gene rearrangement for both T-cell receptor and immunoglobulin light chain IgK. A characteristic of our cases was the lack of expression of the specific B-cell transcription factor, Pax5, which is essential for maintaining the identity and function of mature B cells during late B lymphopoiesis. In the absence of Pax5, B cells in vitro can differentiate into macrophages, dendritic cells, granulocytes, and T/NK cells. Methylation analysis of the Pax5 gene in our cases suggests that its inactivation by this epigenetic event in a committed or mature B cell, before plasma cell differentiation, may well be a common pathogenetic mechanism in mature lymphoid neoplasms with expression of multilineage antigens. In particular, case 1 may represent a mixed NK- and B-cell lineage; and cases 2 and 3 may represent mixed T and B-cell lineage, respectively. Aberrations in the DNA methylation patterns are currently recognized as a hallmark of human cancer. Cases with aberrant phenotypes require molecular analysis for lineage assignment. Studies of such cases may be helpful to better elucidate whether they represent a distinct entity with clinical, immunophenotypic, and molecular characteristics or an incidental phenomenon during malignant transformation. Interestingly, these cases were all characterized by poor clinical outcome. |
DOI | 10.1016/j.humpath.2009.01.007 |
Alternate Journal | Hum. Pathol. |
PubMed ID | 19368954 |