Deletions at 11q identify a subset of patients with typical CLL who show consistent disease progression and reduced survival

Abstract

Eighty-four patients with typical chronic lymphocytic leukemia 27% of patients with B-CLL. [11][12][13] Fegan et al 13 studied 45 (CLL) (by morphological and immunophenotypic criteria) on patients with typical CLL over 5 years and performed cytowhom karyotypes were available were studied. Binet stage at genetic analysis every 6-12 months or more frequently if there diagnosis and follow-up were defined. Survival was calculated was evidence of disease progression. Abnormalities were from diagnosis. Fifty-one percent of patients had a karyotypic detected in 62% at some point during the study with 38% abnormality, the commonest being abnormalities at 13q14 (16%); these patients did not have significantly different surshowing clonal evolution. 11q deletions were found most frevival from patients with normal karyotype. The second comquently in the patients with progressive disease. This original monest abnormality was del(11q) (13%); these patients had sigstudy was extended to an adjacent centre and here we present nificantly worse survival when compared both with patients our updated long-term results. The patients' records were examined and the Binet stage was with CLL have chromosomal abnormalities as detected by noted at diagnosis and any change was documented. Treatcytogenetic analysis 1,2 but few centres perform routine cytogments for CLL were also recorded as were the causes of death. enetic analysis because of the perception that limited prognos-A patient was considered to have had a CLL-related death if tic information can be gained over and above that of the he/she died as a result of cytopenias, high-grade lymphoma Binet/Rai staging. The presence of a clonal abnormality, howor infection; also if CLL was quoted as the cause of death on ever, may be an aid in the diagnosis and assessment of progthe death certificate. Otherwise death was considered nonnosis. Deletions at 13q14 are the most frequent abnormality CLL related. In all cases survival was assessed from diagnosis. in CLL and occur in up to 30% of patients. 2-4 Such patients have been shown to have a similar survival pattern to those with a normal karyotype. 2 Trisomy 12 is another common abnormality, affecting about 20% of patients as determined Diagnosis of CLL by conventional techniques 2 but as many as 30-40% when analysed by FISH, detecting abnormalities in previously norThis required a peripheral lymphocytosis (Ͼ4 × 10 9 /l) of small mal karyotypes. 5,6 Trisomy 12 is thought to be an adverse mature lymphocytes, Ͻ10% prolymphocytes or large lymphoprognostic feature and correlation with atypical morphology cytes and Ͻ15% cleaved or lymphoplasmacytic cells. and poor survival has been shown. 2,6,7 Multiple karyotypic Immunophenotype of typical CLL was needed ie CD5, CD19 abnormalities, a high percentage of abnormal metaphases and and CD23 positive with weak immunoglobulin expression abnormalities of chromosome 14 are also associated with demonstrating or restriction. FMC7 was weak and/or poorer outlook; 2,8-10 at least a proportion of the latter wi...

Comparative genomic hybridization and amplotyping by arbitrarily primed PCR in stage A B-CLL

“…The use of CGH combined with AP-PCR allowed to detect genetic abnormalities in 79% of cases (15/19) with apparently normal or unsuccessful karyotype ( Table 2). As has been reported in previous studies using FISH, in our series losses of 13q and gains of chromosome 12 were the most frequent changes both by CGH and by AP-PCR [1,[4][5][6][7][8][9][10]. These results were confirmed by FISH.…”

“…Genetic studies have provided useful information in understanding the pathogenesis of CLL, and some aberrations may also have a prognostic impact [4][5][6][7][8][9][10]. In CLL, accurate and successful cytogenetic analysis has been hindered by the low in vitro mitotic activity of the critical B-cell population with metaphases arising from normal T-cells being frequent.…”

Array-based karyotyping in chronic lymphocytic leukemia (CLL) detects new unbalanced abnormalities that escape conventional cytogenetics and CLL FISH panel

“…5,15,16,19,32,36 and 50) with 6q loss detected by FISH or arrayCGH were successfully subjected to 32K tiling path chromosome 6 arrayCGH to more precisely define the smallest commonly deleted region (SCDR). We confirmed that the SCDR included 6q21q32 comprising a 1.4 Mb region (Figure 2).…”

“…A subset of genomic aberrations was identified as important independent predictors of disease progression and survival 3 . Deletions of 11q and 17p, affecting the ataxia telangiectasia mutated (ATM) gene and p53 tumor suppressor gene (TP53) respectively, have been associated with disease progression and reduced survival [4][5][6][7] . Early identification of these deletions could allow clinicians to choose appropriate therapy for these patients 8,9 .…”

Frequent deletions at 11q23 and 13q14 in B cell prolymphocytic leukemia (B-PLL)

“…8 These abnormalities define a subset of typical CLL patients that show consistent disease progression and reduced survival. 9 In a recent study, Stilgenbauer et al 10 characterized deletions and translocations involving chromosome bands 11q21-q23. Using a panel of yeast artificial chromosome (YACs) clones organized as a contig, they were able to define a single critical region of 2-3 Mb where all deletions and translocations clustered and that is encompassed by a single YAC clone.…”