Eligible patients were at least 18 years old and previously untreated, and had immunophenotypically confirmed B-cell chronic lymphocytic leukaemia; an Eastern Cooperative Oncology Group (ECOG) performance status score of less than 2; a Binet stage C according to IWCLL 2008 criteria or Binet stage A and B with active disease; no 17p deletion or absence of p53 mutation; and were considered medically fit.
Recently, a new pathogenetic model involving miRNAs and protein coding genes (such as TP53 and ZAP-70) has been identified and explains the prognostic implications of the most recurrent chromosomal abnormalities in human B-cell chronic lymphocytic leukemia.
In this study, we analyzed 149 bone marrow aspirate or peripheral blood specimens from patients diagnosed with B-CLL, evaluated by four different laboratory studies: morphology examination, three- or four-color flow cytometry analysis, conventional cytogenetics, and fluorescence in situ hybridization (FISH) with a dual-color, break-apart IGH@ probe in addition to a B-CLL FISH probe panel for del(11)(q22) ATM, del(13)(q14.3), del(17)(p13) TP53, and +12.
We investigated the gene expression of five key cell cycle regulators: TP 53, c-Myc, cyclin D2, p21WAF1/CIP1 and p27KIP1, which primarily regulate the G1 phase of the cell cycle, or S-phase entry and ultimately control the proliferation and cell growth as well as their role in B-CLL progression.
The functional evaluation of ataxia telangiectasia mutated (ATM) and p53 was recently developed in B-cell chronic lymphocytic leukaemia (B-CLL), a disease in which the response to DNA damage is frequently altered.
Our data provide evidence that 17p loss may play an additional pathogenetic role in B-CLL and suggest that the concomitant loss of multiple tumor suppressor genes could be responsible for the highly adverse prognostic relevance associated with TP53 loss.
Because inactivation of p53 by deletion and/or mutations also impacts on the clinical course of B-cell chronic lymphocytic leukemia (B-CLL), we assessed the role of the SNP309 genotype in B-CLL.
Sixty-five B-CLL patients were investigated using cytogenetics, interphase fluorescence in situ hybridization (FISH), analysis of IgV(H) and of TP53 mutational status before treatment with 2-chloro-2'-deoxyadenosine (CdA).
Translocations or isochromosome formations at sites of low-copy DNA repeats in 17p10 to 17p12 appear to be the mechanism for the loss of TP53 in B-CLL.
TP53 is located at chromosome band 17p13 and its absence can be detected by fluorescence in situ hybridization (FISH) in the interphase nuclei of 8-10% patients with B-CLL.
We conclude that CYC202 is a potent inducer of apoptosis in B-CLL regardless of the functional status of the p53 pathway, and may be considered as a therapeutic agent to improve the outcome of resistant B-CLL tumors.
Wild and mutant forms of p53 protein were evaluated in 197 B-CLL patients at diagnosis or before progression by an immunoenzymatic method in plasma using an anti-p53 monoclonal antibody.
Several candidates, such as mutation of p53 gene and abnormalities of cyclin dependent kinase inhibitor, have been proposed to play an important role in the transformation of a part of B-CLL.
Noteworthy results were obtained when the group of p53 positive B-CLL patients was analyzed according to the percentage of p53 positive cells (less than 20% and more than 20%, respectively).
Simultaneous detection of BCL-2 protein, trisomy 12, retinoblastoma and P53 monoallelic gene deletions in B-cell chronic lymphocytic leukemia by fluorescence in situ hybridization (FISH): relation to disease status.