Trisomy 12 is seen within a specific subtype of B‐cell chronic lymphoproliferative disease affecting the peripheral blood/bone marrow and co‐segregates with elevated expression of CD11a

Abstract

In order to delineate the specific morphological and immunophenotypic features of B-cell lymphoproliferative disorders associated with trisomy 12, 172 sequential unselected cases of CD19 + CD5 + B-cell disorders, primarily affecting the peripheral blood and bone marrow, were studied. Trisomy 12 was found in 24 cases (13.9%), with all cases morphologically classified as either CLL-PL or CLLmixed by FAB criteria. Trisomy 12 was not found in any cases of typical CLL. Trisomy 12 cases demonstrated a significant higher expression of CD11a (P<0.0001) and CD20 (P<0.0006) when compared to cases with the equivalent morphology and immunophenotype, but without the chromosomal abnormality. Trisomy 12 cases also demonstrated a higher frequency of FMC7, CD38 expression and moderate to strong surface immunoglobulin staining. However, no correlation was detected between the percentages of trisomy 12 cells and cells expressing CD11a, CD38, FMC7 or sIg mean fluorescent intensity. Cells from trisomy 12 positive cases were sorted according to their CD11a expression using fluorescent activated cell sorting. There was a significant increase in the percentage of trisomy 12 cells within the CD11a + sorted fraction compared to the unsorted population (P<0.05), implying that trisomy 12 is associated with increased expression of CD11a.With the highly specific morphological and immunophenotypic features demonstrated by trisomy 12 cases in this study, it is highly likely that these cases constitute a specific group of B-cell lymphoproliferative disorders.

Pan B‐cell markers are not redundant in analysis of chronic lymphocytic leukemia (CLL)

“…This finding was somewhat unexpected in light of several studies that have shown an apparent correlation between morphology and immunophenotype (65)(66)(67)(68)(69)(70)(71). In addition, CLL with trisomy 12 has been associated with atypical morphology (65)(66)(67)(68)(69)(70)(71).…”

“…This finding was somewhat unexpected in light of several studies that have shown an apparent correlation between morphology and immunophenotype (65)(66)(67)(68)(69)(70)(71). In addition, CLL with trisomy 12 has been associated with atypical morphology (65)(66)(67)(68)(69)(70)(71). Furthermore, cases of CLL with trisomy 12 have been shown to be associated with an atypical immunophenotype including increased CD20 expression (66,70) and expression of FMC7 (65,68,70,71).…”

“…In addition, CLL with trisomy 12 has been associated with atypical morphology (65)(66)(67)(68)(69)(70)(71). Furthermore, cases of CLL with trisomy 12 have been shown to be associated with an atypical immunophenotype including increased CD20 expression (66,70) and expression of FMC7 (65,68,70,71). The majority of these studies concentrated on the differences between cases of CLL with or without trisomy 12.…”

Trisomy 12 chronic lymphocytic leukemia cells exhibit upregulation of integrin signaling that is modulated by NOTCH1 mutations

“…5,15 The implications of this observation were investigated in a large cohort of patients with trisomy 12 detectable by fluorescence in-situ hybridization. In agreement with previous reports, CLL cases with trisomy 12 had significantly higher expression of CD38 compared with CLL cells from the other major cytogenetic categories (P , .0001) ( Figure 5A).…”

“…4 The increased prevalence of trisomy 12 in these lymphomas is of particular interest in light of studies reporting increased expression of the a-integrins CD11a and CD49d on trisomy 12 CLL cells. 5,6 The heterodimeric integrins CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1), CD49d/CD29 (very late antigen-4 [VLA-4]), and CD49d/ITGB7 are cell surface transmembrane proteins involved in the inducible adhesion of leukocytes to vascular walls during the process of transendothelial migration from the bloodstream into the tissues. This process is particularly important in CLL as it allows the malignant cells to enter lymphoid organs where they receive growth and survival signals and are protected from chemotherapy by a network of interactions with the lymph node (LN) microenvironment.…”