New translocations in a case of atypical B-cell chronic lymphocytic leukemia: involvement of ATM, MLL, and TP53 genes

Collado, Rosa; Hueso, José Antonio; Cabello, A; Oliver, Isabel; Egea, Mercedes; Orero, Maite; Miguel-Sosa, A; Cigudosa, Juan C.; Benítez, Javier; Barragán, Eva; Carbonell, Félix

doi:10.1016/j.cancergencyto.2006.02.021

Cited by 4 publications

(3 citation statements)

References 8 publications

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“…Our data were consistent with these findings, where defective p53 derived from TP53 deletion in CLL cells resulted in an increased level of 8-oxo-dG. The occurrence of important oxidized DNA base concentrations among patients with deletions and/or mutations of TP53 in CLL may explain the poor prognosis observed in these cases, in addition to the involvement of TP53 alterations in complex karyotypes [15, 16]. Furthermore, the observed DNA damage in the normal FISH group could contribute to the emergence of karyotypic aberrations with adverse prognostic features that have been previously described by Rigolin et al [17] in one-third of CLL patients with normal FISH.…”

Section: Resultssupporting

confidence: 90%

Increased Oxidative Damage Associated with Unfavorable Cytogenetic Subgroups in Chronic Lymphocytic Leukemia

Collado

Ivars

Oliver

et al. 2014

BioMed Research International

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Oxidative stress contributes to genomic instability in chronic lymphocytic leukemia (CLL), but its relationship with the acquisition of specific chromosomal abnormalities is unknown. We recruited 55 untreated CLL patients and assessed 8-oxo-2′-deoxyguanosine (8-oxo-dG), glutathione, and malondialdehyde (MDA) levels, and we compared them among the cytogenetic subgroups established using fluorescence in situ hybridization (FISH). Significant increases in 8-oxo-dG and/or MDA were observed in patients with unfavorable cytogenetic aberrations (17p and 11q deletions) compared to the 13q deletion group. TP53 deletion patients exhibited a diminished DNA repair efficiency. Finally, cases with normal FISH also showed enhanced 8-oxo-dG, which could result in adverse outcomes.

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Section: Resultssupporting

confidence: 90%

Increased Oxidative Damage Associated with Unfavorable Cytogenetic Subgroups in Chronic Lymphocytic Leukemia

Collado

Ivars

Oliver

et al. 2014

BioMed Research International

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“…For the purpose of the study, only 25 patients with translocations involving 13q14 with available samples were included; 21 had been diagnosed as CLL and four were MBL. One patient was previously reported (Collado et al, ). Moreover, two additional groups of patients were selected for comparison of clinical and biological data.…”

Section: Methodsmentioning

confidence: 94%

Interstitial 13q14 deletions detected in the karyotype and translocations with concomitant deletion at 13q14 in chronic lymphocytic leukemia: Different genetic mechanisms but equivalent poorer clinical outcome

Puiggros¹,

Venturas

Salido

et al. 2014

Genes Chromosomes & Cancer

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Deletion of 13q14 as the sole abnormality is a good prognostic marker in chronic lymphocytic leukemia (CLL). Nonetheless, the prognostic value of reciprocal 13q14 translocations [t(13q)] with related 13q losses has not been fully elucidated. We described clinical and biological characteristics of 25 CLL patients with t(13q), and compared with 62 patients carrying interstitial del(13q) by conventional G-banding cytogenetics (CGC) [i-del(13q)] and 295 patients with del(13q) only detected by fluorescence in situ hybridization (FISH) [F-del(13q)]. Besides from the CLL FISH panel (D13S319, CEP12, ATM, TP53), we studied RB1 deletions in all t(13q) cases and a representative group of i-del(13q) and F-del(13q). We analyzed NOTCH1, SF3B1, and MYD88 mutations in t(13q) cases by Sanger sequencing. In all, 25 distinct t(13q) were described. All these cases showed D13S319 deletion while 32% also lost RB1. The median percentage of 13q-deleted nuclei did not differ from i-del(13q) patients (73% vs. 64%), but both were significantly higher than F-del(13q) (52%, P < 0.001). Moreover, t(13q) patients showed an increased incidence of biallelic del(13q) (52% vs. 11.3% and 14.9%, P < 0.001) and higher rates of concomitant 17p deletion (37.5% vs. 8.6% and 7.2%, P < 0.001). RB1 involvement was significantly higher in the i-del(13q) group (79%, P < 0.001). Two t(13q) patients (11.8%) carried NOTCH1 mutations. Time to first treatment in t(13q) and i-del(13q) was shorter than F-del(13q) (67, 44, and 137 months, P = 0.029), and preserved significance in the multivariate analysis. In conclusion, t(13q) and del(13q) patients detected by CGC constitute a subgroup within the 13q-deleted CLL patients associated with a worse clinical outcome.

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“…Benzene and its metabolites as well as ionising radiation (IR) are known to be associated with acute myeloid leukaemia (AML) (1,3) and a recent case report study referring to occupational exposure to HQ may support such a possibility (13). Increased risk of AML and cancer predisposition in general is linked with certain inherited conditions such as Ataxia Telangiectasia and Nijmegen breakage syndrome (16,17). Interestingly, these conditions are also associated with excessive chromosomal fragility, which appears either spontaneously or following G2-phase irradiation of peripheral blood lymphocytes (PBL).…”

Section: Introductionmentioning

confidence: 99%

The benzene metabolite hydroquinone enhances G2-chromosomal radiosensitivity by inducing a less-efficient G2-M-checkpoint in irradiated lymphocytes

Hatzi

Terzoudi²,

Pantelias³

et al. 2007

Int J Oncol

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Abstract. The hypothesis tested is that a 24-h pre-irradiationexposure of peripheral blood lymphocytes (PBL) to the benzene metabolite hydroquinone (HQ), at doses that are nonacutely toxic (5 μM), induces a less efficient G2-M-checkpoint and enhances the G2-chromosomal radiosensitivity in a statistically significant manner (p<0.01). A less efficient G2-Mcheckpoint may allow the transition of damaged cells from G2-to M-phase and experimental data in the present work support this hypothesis. In fact HQ sensitizes lymphocytes obtained from healthy donors, as they exhibit increased G2-chromosomal radiosensitivity which interestingly is similar to that observed in cases of radiosensitive cancer-prone individuals. This finding is important since a deficiency in cell cycle checkpoints and an increase in G2-chromosomal radiosensitivity are linked to chromosomal instability, cancer proneness and the development of leukemia. The observed chromosome radiosensitization may be a consequence either of an effect of HQ on the initial induction of radiation-induced chromosomal aberrations, or on the DNA repair capacity of the cells, or it may be linked to HQ-induced alterations in the cell cycle and feedback control mechanism during the G2-to M-phase transition. In order to elucidate which is the mechanism involved, conventional cytogenetics and premature chromosome condensation (PCC) methodologies were applied. The experimental data obtained support the hypothesis that HQ increases G2-chromosomal radiosensitivity in human peripheral blood lymphocytes by inducing a less efficient G2-M-checkpoint, facilitating thus the transition of damaged cells from G2-to M-phase.

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New translocations in a case of atypical B-cell chronic lymphocytic leukemia: involvement of ATM, MLL, and TP53 genes

Cited by 4 publications

References 8 publications

Increased Oxidative Damage Associated with Unfavorable Cytogenetic Subgroups in Chronic Lymphocytic Leukemia

Increased Oxidative Damage Associated with Unfavorable Cytogenetic Subgroups in Chronic Lymphocytic Leukemia

Interstitial 13q14 deletions detected in the karyotype and translocations with concomitant deletion at 13q14 in chronic lymphocytic leukemia: Different genetic mechanisms but equivalent poorer clinical outcome

The benzene metabolite hydroquinone enhances G2-chromosomal radiosensitivity by inducing a less-efficient G2-M-checkpoint in irradiated lymphocytes

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