Chromosome aberrations in atypical chronic lymphocytic leukemia: a cytogenetic and interphase cytogenetic study

Abstract

To define better the chromosomal profile of atypical chronic karyotype may in fact carry chromosomally abnormal clones lymphocytic leukemia (aCLL), cytogenetic and interphase cytoescaping detection at metaphase analysis due to their low genetic studies were performed in 43 cases, using mitogenmitotic index. a relatively poor prognosis may be associated with aCLL.The presence of ؉12, 13q14 deletions, 11q, and 6q21-q23 anomalies in 19 cases was associated with a 2-month median interTo define better the cytogenetic profile of aCLL, this study val between diagnosis and start of treatment, as compared with of 43 cases was carried out combining conventional chromoa 24-month median interval in 14 cases with normal karyotype some analysis (CCA) and FISH, using probes detecting the two or non-recurrent chromosome changes (P ‫؍‬ 0.003). We conmost frequent anomalies in CLL, ie +12 and del(13q14).clude that aCLL is characterized by a relatively high incidence of chromosome anomalies, with recurrent chromosome changes, involving chromosomes 12, 13q14, 6q21q23, 11q, selected on the basis of the presence of more than 10% large Keywords: atypical CLL; cytogenetics; FISH lymphocytes and/or prolymphocytes (see below) among approximately 260 B-CLLs, seen at our Institution over a 9-year period. Materials and methods IntroductionDiagnoses were made in all cases according to standard clinical, cytologic and immunologic criteria. Histologic studThe importance of cytogenetics of B cell chronic lymphocytic ies were performed for diagnostic purposes in 27 cases (bone leukemia (CLL) has been highlighted over the past 10 years biopsy in 19 cases and superficial lymph node biopsy in eight in a number of studies, reviewed by Juliusson and Gahrton, 1 cases). Transformation of aCLL into prolymphocytic leukemia documenting that some chromosome changes, such as tri-(PLL) was not an exclusion criteria, whereas those patients somy 12, del (11q) or 14q anomalies are associated with therpresenting with 'de novo' PLL were not considered in this apy-demanding disease and, ultimately, with shorter survival.

Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712)

“…57,58 Recent studies examining molecular aberrations, including p53 mutations, unfavorable cytogenetics, CD38 expression, and somatic variable-heavy (VH) gene mutational status, have demonstrated that these are also important determinants for treatment outcome in CLL. [42][43][44][45][46][47][48][49][50][59][60][61][62][63][64][65][66] It is of interest that several standard prognostic factors, including age, Rai stage, and B 2 M level, were not shown to be important in predicting treatment outcome for the group of patients treated in this trial. Similar results with respect to the lack of importance of age to treatment outcome have been observed in the 2 trials examining altered dosing of rituximab therapy in previously treated patients with CLL.…”

“…40,41 Overexpression of several antiapoptotic proteins (mcl-1, bag-1) and the presence of specific genetic aberrations [p53 mutations, ataxia telangiectasia gene mutations, and interphase cytogenetic abnormalities including del(17p13)] have been associated with poor response to fludarabine-based therapy. [42][43][44][45][46][47][48][49][50] One of the attractive features of immunotherapy with monoclonal antibodies, such as rituximab, is that the proposed mechanism of cell clearance is different from that of cytotoxic chemotherapy, involving both complement-mediated cell lysis and antibody-dependent cellular cytotoxicity. [51][52][53] However, recent evidence shows that a portion of CLL patients receiving rituximab treatment have in vivo activation of caspase-9, caspase-3, and poly-adenosine-5Ј-diphosphate-ribose polymerase (PARP) cleavage in blood leukemia cells immediately following treatment.…”

Cyclin D1: polymorphism, aberrant splicing and cancer risk

“…Interestingly, cyclin D1 alterations are tumor-type specific, and occur through chromosomal translocation, gene amplification, or excessive accumulation of the protein. Chromosomal translocation of cyclin D1 is relatively rare in most cancers, but occurs in greater than 90% of Mantle Cell lymphoma, a mature B-cell malignancy (Bosch et al, 1994;De Wolf-Peeters and Pittaluga, 1994;Bigoni et al, 1996). This same translocation (11;14)(q13;q32) is also observed at a lower frequency mutliple myeloma and specific leukemias (Bosch et al, 1994;Bergsagel and Kuehl, 2005).…”

MicroRNA BIOGENESIS, FUNCTIONALITY AND CANCER RELEVANCE

“…Deletion of the 13q14 region occurs in more than half of the cases of B cell chronic lymphocytic leukemias and also in 50 % of mantle cell lymphomas, in 16-40 % of multiple myelomas and in 60 % of prostate cancers, suggesting that tumor suppressor(s) gene(s) at 13q14 are involved in the pathogenesis of these tumors 64,65,66,67 . Calin et al (2002) have shown that two miRNA genes are located at 13q14.3 within a 30-kb region of minimal loss in CLL between two exons of the LEU2 gene.…”