Rare lymphoid neoplasms coexpressing B- and T-cell antigens. The role of PAX-5 gene methylation in their pathogenesis.
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.
Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy.
Stefano
S
Lazzi
Cristiana
C
Bellan
Anna
A
Onnis
Giulia
G
De Falco
Shahin
S
Sayed
Ioannis
I
Kostopoulos
Monica
M
Onorati
Alessandro
A
D'Amuri
Rosa
R
Santopietro
Carla
C
Vindigni
Alberto
A
Fabbri
Simona
S
Righi
Stefano
S
Pileri
Piero
P
Tosi
Lorenzo
L
Leoncini
D000368:Aged; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D019175:DNA Methylation; D017809:Fatal Outcome; D005260:Female; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000235:genetics; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology; D008223:Lymphoma / Q000209:etiology* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism*
D000941:Antigens; D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D051757:PAX5 Transcription Factor