The presence of high‐risk chromosome aberrations in chronic lymphocytic leukaemia does not correlate with centrosome aberrations

Abstract

Chromosome aberrations are frequently found in B-cell chronic lymphocytic leukaemia (B-CLL), and specific chromosome aberrations identify poor prognostic subgroups. Almost all the aberrations identified in B-CLL involve loci where genes with a role in the regulation of centrosome duplication have been mapped. Centrosome aberrations have been described as a possible cause of numerical chromosome abnormalities in both solid and haematological tumours. However, little is known about the possible role of centrosome aberrations in B-CLL. To investigate whether centrosome aberrations do occur in B-CLL and correlate with cytogenetically defined prognostic subgroups, we examined a set of 64 B-CLL samples by immunofluorescent staining. B-CLL cases differed significantly from controls in the mean frequency of cells with centrosome aberrations, while no difference was found between subgroups with or without specific chromosome aberrations. Our results indicated that although centrosome aberrations were a common feature in B-CLL, they did not represent a reliable prognostic marker.

A Clinical Overview of Centrosome Amplification in Human Cancers

“…However, there is no correlation with IgVH gene mutation status or cytogenetically-defined risk groups (11q22-23, 17p13 and 13q14 deletions; trisomy 12). This is corroborated with the finding that no difference exists between CLL subgroups with or without the same specific chromosome aberrations with prognostic significance 180.…”

Controlled trials of vitamin D, causality and type 2 statistical error

“…A clinical trial of vitamin D for CLL might show benefits but benefits could not necessarily be expected at a late stage in the disease. This is because CLL may be caused many years before it is picked up by expansion of the white cell population with fixation of chromosome aberrations ( 17 ) and failure of regulation by apoptosis which may involve vitamin D metabolism ( 18 ) . These mutated white cells can not necessarily be expected to respond normally to vitamin D provided at a later stage.…”

Cytokinesis arrest and multiple centrosomes in B cell chronic lymphocytic leukaemia

“…This finding is in accordance with previous reports showing that leukaemic cancers often exhibit multiple centrosomes. 32,33 Interestingly, when we performed transient siRNAmediated knockdown of TP53 in healthy donor CD19+ cells (Figure 6 and Supporting Information), we could show that knockdown of TP53 resulted in a phenotype that highly resembled CLL cells with multiple centrosomes and accumulation of cells arrested in cytokinesis. Taken together, our results indicate that reduced NuMA and TP53 levels may contribute to the cytokinesis defects described in this study.…”