Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among 75 untreated patients with typical (CD19+, CD5/CD19+, CD23/CD19+) B-cell chronic lymphocytic leukemia (B-CLL) cytogenetic aberrations of peripheral blood cells were evaluated, using fluorescence in situ hybridization techniques. Two cytogenetic aberrations were evaluated: trisomy 12 and TP53 deletion. The clonality was determined when > or = 10% of the cells had of trisomy 12 or deletion TP53 gene. Trisomy 12 in 7 patients was detected, while trisomy 12 and TP53 deletion simultaneously in 6 patients were present. If the first group will be linked to the second one then 13 patients among 75 (17%) will have trisomy 12. In group of patients with trisomy 12 and TP53 deletion percentage of cells with trisomy 12 was almost two time more compare to patients with trisomy 12 as a single aberration. It is possible, that TP53 deletion ("the guardian of the genome") facilitates proliferation clones with others genomic aberrations. In two patients with trisomy 12 control cytogenetic study was performed. Increase of percentage cells with trisomy 12 for 8% and 30% respectively was detected. However, proliferation of cells with TP53 deletion was observed too. Clinical course of B-CLL in group of patient with trisomy 12, trisomy 12 and TP53 deletion simultaneously is more aggressive compared to the course of disease of patients with no cytogenetic aberrations (patients of Group I from Part I of paper). Frequency of IGHV gain mutation occurrence was not analyzed in both groups of patients. But trisomy 12 together with unmutated IGHV gene is found by some authors. The absence IGHV gene mutation is independent unfavourable prognostic factor.
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PMID:[Some genomic aberrations in B-cell chronic lymphocytic leukemia and their clinical relevance. Part II. Trisomy 12 in B-cell chronic lymphocytic leukemia detected by fluorescence in situ hybridization]. 1505 38

The most frequent chromosomal abnormalities in B-cell chronic lymphocytic leukemia (B-CLL) are deletions on 13q14 and 17p13, trisomy 12, and 14q32 rearrangement. Conventional cytogenetic analysis underestimates the frequency of specific chromosome aberrations in B-CLL because of the low rate of spontaneous mitoses and the poor response to mitogen stimulation. We used interphase fluorescence in situ hybridization (I-FISH) to explore the incidence of chromosomal changes in the peripheral blood cells of B-CLL patients. Probes for 13q14 (D13S319), 17p13 (p53), the centromere of chromosome 12 (CEP12), and 14q32 (IGHC/IGHV) were applied to detect chromosomal aberrations in peripheral blood samples from 83 B-CLL patients (60 men, 23 women). Molecular cytogenetic aberrations were found in 61 cases (73.5%), and 8 patients (9.6%) showed 2 kinds of abnormalities. The most frequent abnormality was deletion of 13q14 (41.0%), followed by +12 (19.3%), deletion of 17p13 (12%), and 14q32 rearrangement (9.6%). FISH results were analyzed for correlation with Binet stages. The percentages of patients who showed abnormalities by FISH were 73.0%, 73.3%, and 80% for Binet stages A, B, and C, respectively, and the percentages of patients with abnormalities who showed 2 anomalies were 7.9%, 27.3%, and 0% for Binet stages A, B, and C, respectively. We noted no consistent pattern among the various Binet stages in the distribution of either the types of FISH-detected anomalies or the numbers of FISH anomalies. I-FISH was found to be a rapid, exact, and sensitive technique for analysis of chromosome aberrations in CLL. FISH could provide accurate information regarding the molecular cytogenetic features of CLL.
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PMID:Interphase fluorescence in situ hybridization detection of cytogenetic abnormalities in B-cell chronic lymphocytic leukemia. 1756 21

Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic monoclonal expansion of <5.0 x 10(9)/l circulating CLL-phenotype B-cells. The relationship between MBL and Rai 0 CLL, as well as the impact of biological risk factors on MBL prognosis, are unknown. Out of 460 B-cell expansions with CLL-phenotype, 123 clinical MBL (cMBL) were compared to 154 Rai 0 CLL according to clinical and biological profile and outcome. cMBL had better humoral immune capacity and lower infection risk, lower prevalence of del11q22-q23/del17p13 and TP53 mutations, slower lymphocyte doubling time, and longer treatment-free survival. Also, cMBL diagnosis was a protective factor for treatment risk. Despite these favourable features, all cMBL were projected to progress, and lymphocytes <1.2 x 10(9)/l and >3.7 x 10(9)/l were the best thresholds predicting the lowest and highest risk of progression to CLL. Although IGHV status, CD38 and CD49d expression, and fluorescence in situ hybridization (FISH) karyotype individually predicted treatment-free survival, multivariate analysis identified the presence of +12 or del17p13 as the sole independent predictor of treatment requirement in cMBL (Hazard ratio: 5.39, 95% confidence interval 1.98-14.44, P = 0.001). Overall, these data showed that cMBL has a more favourable clinical course than Rai 0 CLL. Given that the biological profile can predict treatment requirement, stratification based on biological prognosticators may be helpful for cMBL management.
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PMID:The prognosis of clinical monoclonal B cell lymphocytosis differs from prognosis of Rai 0 chronic lymphocytic leukaemia and is recapitulated by biological risk factors. 1943 85

Hairy cell leukemia (HCL) is generally responsive to single-agent cladribine, and only a minority of patients are refractory and with poor prognosis. HCLs generally express mutated (M) and, in a minority, unmutated (UM) IGHV. In a multicenter clinical trial in newly diagnosed HCL, we prospectively investigated clinical and molecular parameters predicting response and event-free survival after single-agent cladribine. Of 58 HCLs, 6 expressed UM-IGHV (UM-HCL) and 52 M-IGHV (M-HCL). Beneficial responses were obtained in 53 of 58 patients (91%), whereas treatment failures were observed in 5 of 58 patients (9%). Failures were associated significantly with UM-IGHV (5 of 5 failures vs 1 of 53 beneficial responses had UM-IGHV, P < .001), leukocytosis (3 of 5 vs 3 of 53, P = .006), and bulky spleen (4 of 5 vs 4 of 53, P < .001). The UM-HCL not benefiting from cladribine characteristically had bulky spleen (4 of 5, 80%), leukocytosis (3 of 5, 60%), and TP53 defects (2 of 5, 40%), and progressed rapidly after first treatment (median event-free survival, 7.5 months). Our data suggest that UM-HCLs identify the minor subgroup failing cladribine treatment and with more aggressive disease. High incidence of TP53 dysfunction indicates a potential mechanism of resistance to cladribine in the UM-HCL group. Overall, our data provide new molecular elements relevant for treatment concerns in HCL.
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PMID:Hairy cell leukemias with unmutated IGHV genes define the minor subset refractory to single-agent cladribine and with more aggressive behavior. 1996 13

We conducted a retrospective collaborative study to cytogenetically characterize splenic marginal zone lymphoma (SMZL) and ascertain the prognostic value of chromosomal aberrations. Of 330 cases, 72% displayed an aberrant karyotype, 53% were complex, and 29% had a single aberration. The predominant aberrations were gains of 3/3q and 12q, deletions of 7q and 6q and translocations involving 8q/1q/14q. CD5 expression was detected in 39 of 158 cases (25%). The cytogenetic makeup of the CD5(+) group differed significantly from that of the CD5(-) group. Cases with unmutated IGHV were significantly associated with deletions of 7q and TP53. A strong association was noted between usage of the IGVH1-2 and deletion 7q, 14q alterations, and abnormal karyotype. On univariate analysis, patients with more than or equal to 2 aberrations, 14q alterations, and TP53 deletions had the shortest survival; 7q deletion did not affect survival. On multivariate analysis, cytogenetic aberrations did not retain prognostic significance; the parameters negatively affecting survival were hemoglobin and age. In conclusion, the cytogenetic profile of SMZL is distinct from other B-cell lymphomas. Complexity of the karyotype, 14q aberrations, and TP53 deletions are poor prognostic indicators and may be considered together with other clinicobiologic parameters to ascertain the prognosis of SMZL.
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PMID:Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group. 2047 88

Multiple myeloma (MM) is a neoplasm of a terminally differentiated B-cell. Human myeloma cell lines were shown to be suitable model systems for use in various fields of the biological sciences. This study was aimed to investigate the genetic aberrations in human multiple myeloma cell lines. Interphase fluorescence in situ hybridization (FISH) with probes for the regions containing 13q14 (RB-1), 13q14.3 (D13S19), 14q32 (IGHC/IGHV) , 1q12 (CEP1), 17p13 (TP53) were was used to detect 7 HMCL and 85 cases of newly diagnosed MM. FISH with LSI IGH/CCND1 , LSI IGH/FGFR3 and LSI IGH/MAF probes were used to detect t(11;14) (q13;q32) , t(4;14) (p16;q32) and t(14;16) (q32;q23) in HMCL and MM with 14q32 rearrangement. The results showed that molecular cytogenetic aberrations were found in all 7 HMCL, six (85.7%) HMCL simultaneously had 13q14, 13q14.3 deletion. Chromosome 1q21 abnormality was found in six (33.3%) HMCL with at least 3 copies amplifications. Illegitimate 14q32 rearrangement was found in five (71.4%) HMCL, including one with t(11;14), two with t(4;14) and three with t(14;16). 17p13 deletion was detected in 5 HMCL. Chromosomal changes were observed in 85.9% of the 85 cases of newly diagnosed MM. The del(13), 1q12 amplification, del(17p), 14q32 rearrangement, t(11;14), t(4;14), t(14;16) were present in 44.7%, 52.9%, 20%, 62.4%, 27.1%, 24.7% and 3.5% of the patients respectively. There was no significant difference in the prevalence of genetic abnormalities of del(13q), 14q32 rearrangement, 1q12 amplification, t(11;14), t(4;14) except del(17p) and t(14;16). It is concluded that HMCL representative of the most aggressive phase of plasma cell neoplasms accumulated a large amount of genetic aberrations. Loss of p53 are strikingly common in HMCL suggesting that the impairment of the P53 tumor suppressor pathway is an important contributor to extramedullary tumor expansion.
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PMID:[Comparative study of genetic aberrations in human multiple myeloma cell lines and newly diagnosed MM by fluorescence in situ hybridization]. 2117 60

Recurrent losses or gains of genomic material as well as mutations of key tumor suppressors (ATM and TP53) have been identified in chronic lymphocytic leukemia (CLL). These aberrations are important "drivers" of the disease and some of its clinical characteristics. There is a remarkable heterogeneity in the clinical course between patient subgroups with distinct genetic features. While some mutations are associated with poor outcome (particularly 17p- and TP53 mutation and to a lesser extend 11q-) others are linked to a favorable outcome (13q- as sole aberration; mutated IGHV). Our improved understanding of the clinical course of specific genetic subgroups is beginning to be translated into genotype specific treatment approaches where genetic subgroups (e.g. 17p-) are channeled into separate treatment protocols. This review will summarize the most important genetic aberrations in CLL and how our improved knowledge of the genetic make-up of leukemic cells may translate into improved treatment results.
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PMID:Importance of genetics in chronic lymphocytic leukemia. 2143 57

To determine whether prognostic factors remain relevant to chronic lymphocytic leukemia (CLL) patients treated with fludarabine and cyclophosphamide (FC), we prospectively evaluated 86 Chinese CLL patients who received FC in first-line therapy. Twenty-four patients (27.9%) achieved complete remission (CR), and overall response rate was 75.6%. With a median follow-up of 41 months, the median progression-free survival (PFS) was 36.0 months and median overall survival (OS) has not been reached. The strong correlations of lower CR rate with advanced Binet stage, unmutated IGHV, cytogenetic abnormalities of del(17p13) or del(11q23), and p53 mutations were observed by univariable analyses. Stepwise logistic regression identified that unmutated IGHV and p53 abnormality (p53 deletion or mutation) were associated with a decreased odds of achieving CR. The less cycles of treatment, not achieving CR, advanced Binet stage, and p53 abnormality significantly correlated with a shortened PFS. Furthermore, in a multivariate analysis, p53 abnormality and advanced Binet stage were identified as being significant risk factors for early relapse. Not achieving CR, advanced Binet stage, ZAP-70-positive, and p53 abnormality were the adverse factors in determining OS. Only p53 aberration was independently associated with significantly shorter OS by a multivariate analysis. These results suggest that patients with p53 abnormality should be considered for alternative therapies.
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PMID:Comprehensive assessment of prognostic factors predicting outcome in Chinese patients with chronic lymphocytic leukemia treated with fludarabine and cyclophosphamide. 2188 78

Mantle cell lymphoma (MCL) is an aggressive neoplasm with a short survival. Cases with leukaemic MCL and splenomegaly without adenopathies (non-nodal MCL) may have a more indolent course. To gain insights into the biological features underlying this presentation, we investigated the gene expression profile (GEP) and the IGHV mutational status in a cohort of leukaemic MCL cases. Comparison of MCL with other lymphoproliferative disorders (i.e. splenic marginal zone lymphoma, follicular lymphoma, chronic lymphocytic leukaemia) revealed a MCL signature enriched for the following gene categories: mitochondrion, oxidoreductase activity, response to stress, to DNA damage and TP53-pathway. Furthermore, GEP analysis revealed that non-nodal MCL cases were characterized by the down-modulation of the following gene categories: cell projection, actin cytoskeleton organization, cell adhesion (ITGAE, CELSR1, PCDH9) and tumour invasion/progression (PGF, ST14, ETS1, OCIAD1, EZR). Many down-modulated genes were related to the TP53-pathway and to DNA damage response. IGHV status proved unmutated in all nodal and mutated in all non-nodal MCL. Non-nodal leukaemic MCLs display a peculiar clinical presentation, with distinctive biological features, such as mutated IGHV and a transcriptional profile lacking tumour invasion properties, that might contribute to the absence of nodal involvement and to the less aggressive clinical course.
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PMID:Behind the scenes of non-nodal MCL: downmodulation of genes involved in actin cytoskeleton organization, cell projection, cell adhesion, tumour invasion, TP53 pathway and mutated status of immunoglobulin heavy chain genes. 2215 Jan 24

The analysis of chromosomal abnormalities provides significant prognostic information in patients with chronic lymphocytic leukaemia (CLL), a disease with a highly heterogeneous clinical course. Chromosomal abnormalities commonly found are trisomy 12, del(13)(q14), del(11)(q22-23), del(17)(p13) and del(6)(q21). Translocations are present in some patients and affect regions recurrently involved in CLL. This report describes the clinical and pathological characteristics of four CLL patients showing a new recurrent chromosomal abnormality dic(8;17)(p11;p11), that implied loss of the TP53 gene in all cases. In addition, TP53 gene was mutated in three out of four patients. Mechanically, Low Copy Repeats (LCR) in 17p12 and 8p11 may explain the origin of the translocation by non-allelic homologous recombination (NAHR). Isolated dic(8;17)(p11;p11) in patients with mutated IGHV genes status may not have the same prognostic impact as other mutations or deletions affecting the TP53 gene. Larger series are needed to better evaluate the clinical impact of this chromosomal aberration during the course of the disease.
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PMID:A new genetic abnormality leading to TP53 gene deletion in chronic lymphocytic leukaemia. 2215 Mar 35


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