scholarly journals Coexistence of trisomy 12 and del(13)(q14.3) in two patients with chronic lymphocytic leukemia

2009 ◽  
Vol 61 (4) ◽  
pp. 607-611
Author(s):  
Marija Dencic-Fekete ◽  
D. Antic ◽  
Sanja Davidovic-Mrsic ◽  
Ivana Franic ◽  
Nada Kraguljac-Kurtovic ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Prognostic Significance ◽  
Lymphocytic Leukemia ◽  
Stable Phase ◽  
Fish Analysis ◽  
Fluo Rescence ◽  
Trisomy 12 ◽  
One Year ◽  
The Given

We describe two patients with diagnosis of chronic lymphocytic leukemia (CLL) in whom interphase fluo?rescence in situ hybridization (FISH) analysis revealed trisomy 12 and del(13)(q14.3) occurring in the same clone. These abnormalities are rarely seen together and the prognostic relevance of their coexistence is still unclear. According to some data, a probable adverse prognosis for this group of patients is suggested. Our patients have been in a stable phase of the disease for more than one year since the given abnormalities were documented in their karyotypes. Further study is necessary to determine the prognostic significance of coexistence of these abnormalities in CLL patients.

scholarly journals A high-resolution allelotype of B-cell chronic lymphocytic leukemia (B-CLL)

Blood ◽  
2002 ◽  
Vol 100 (5) ◽  
pp. 1787-1794 ◽  
Author(s):  
Urban Novak ◽  
Elisabeth Oppliger Leibundgut ◽  
Jörg Hager ◽  
Dominique Mühlematter ◽  
Martine Jotterand ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Chromosomal Aberrations ◽  
Cytogenetic Analysis ◽  
Prognostic Significance ◽  
Genetic Alterations ◽  
Lymphocytic Leukemia ◽  
Accurate Information ◽  
Trisomy 12 ◽  
Cell Chronic Lymphocytic Leukemia

The most frequent chromosomal aberrations in B-cell chronic lymphocytic leukemia (B-CLL) are deletions on 13q, 11q, and 17p, and trisomy 12, all of which are of prognostic significance. Conventional cytogenetic analysis and fluorescence in situ hybridization (FISH) are used for their detection, but cytogenetic analysis is hampered by the low mitotic index of B-CLL cells, and FISH depends on accurate information about candidate regions. We used a set of 400 highly informative microsatellite markers covering all chromosomal arms (allelotyping) and automated polymerase chain reaction (PCR) protocols to screen 46 patients with typical B-CLL for chromosomal aberrations. For validation, we compared data with our conventional karyotype results and fine mapping with conventional single-site PCR. All clonal cytogenetic abnormalities potentially detectable by our microsatellite PCR (eg, del13q14 and trisomy 12) were picked up. Allelotyping revealed additional complex aberrations in patients with both normal and abnormal B-CLL karyotypes. Aberrations detectable in the samples with our microsatellite panel were found on almost all chromosomal arms. We detected new aberrant loci in typical B-CLL, such as allelic losses on 1q, 9q, and 22q in up to 25% of our patients, and allelic imbalances mirroring chromosomal duplications, amplifications, or aneuploidies on 2q, 10p, and 22q in up to 27% of our patients. We conclude that allelotyping with our battery of informative microsatellites is suitable for molecular screening of B-CLL. The technique is well suited for analyses in clinical trials, it provides a comprehensive view of genetic alterations, and it may identify new loci with candidate genes relevant in the molecular biology of B-CLL.

scholarly journals Monosomy 12 and deletion of 13q34 in a case of chronic lymphocytic leukemia with concomitant lung cancer

2010 ◽  
Vol 67 (10) ◽  
pp. 864-866 ◽  
Author(s):  
Darko Antic ◽  
Marija Dencic-Fekete ◽  
Dragica Tomin ◽  
Irena Djunic
Keyword(s):  
Lung Cancer ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Lung Carcinoma ◽  
Prognostic Significance ◽  
Specific Treatment ◽  
Lymphocytic Leukemia ◽  
Simultaneous Occurrence ◽  
Hybridization Technique

Background. We described a patient with chronic lymphocytic leukemia (CLL) and lung cancer and unusual chromosomal aberrations. Case report. At the same time with the diagnosis of B-cell CLL, squamocellular lung carcinoma diagnosis was established. Using interphase fluoresecence in situ hybridization technique (FISH) we detected monosomy 12 and deletion of 13q34 occured in the same clone. One month after the beginning of examination the patient died unexpectedly during sleep immediately before we applied a specific treatment for CLL or lung carcinoma. Conclusion. Simultaneous occurrence of monosomy 12 and deletion of 13q34 in a patient with B-cell CLL has been described only once before, but as a part of a complex karyotype. The prognostic significance of these abnormalities remains uncertain.

scholarly journals Detection of trisomy 12 by fluorescent in situ hybridization (FISH) in chronic lymphocytic leukemia

2000 ◽  
Vol 23 (3) ◽  
pp. 531-533 ◽  
Author(s):  
Maria de Lourdes L.F. Chauffaille ◽  
Eliana Azevedo Marques ◽  
Jose Salvador Rodrigues de Oliveira ◽  
Maria Madalena Rodrigues ◽  
Maria Stella Figueiredo ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chronic Lymphocytic Leukemia ◽  
Fluorescent In Situ Hybridization ◽  
Molecular Cytogenetics ◽  
Lymphocytic Leukemia ◽  
Specific Method ◽  
Alpha Satellite ◽  
Trisomy 12 ◽  
Mature Lymphocyte

Chronic lymphocytic leukemia (CLL) presents a varying incidence of karyotypic abnormalities whose detection is complicated by difficulties in obtaining mitosis for analysis in this type of mature lymphocyte disorder. Since the introduction of molecular cytogenetics (FISH = fluorescent in situ hybridization), applying centromeric probes for chromosome 12 has made it possible to detect a higher percentage of trisomy 12 cases. The objective of the present study was to detect trisomy 12 by FISH (alpha satellite probe) in 13 patients with CLL whose karyotypes by G-banding were either normal or inadequate. Using this method trisomy 12 was detected in three patients in a percentage of positive cells varying from 55.5% to 79%, showing that FISH is a sensitive and highly specific method for trisomy detection and should be routinely performed when the karyotype is normal.

scholarly journals Detection of trisomy 12 in chronic lymphocytic leukemia by fluorescence in situ hybridization to interphase cells: a simple and sensitive method

Blood ◽  
1992 ◽  
Vol 79 (7) ◽  
pp. 1796-1801 ◽  
Author(s):  
J Anastasi ◽  
MM Le Beau ◽  
JW Vardiman ◽  
AA Fernald ◽  
RA Larson ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chronic Lymphocytic Leukemia ◽  
Fluorescence In Situ Hybridization ◽  
Cytogenetic Analysis ◽  
Normal Karyotype ◽  
Lymphocytic Leukemia ◽  
Chromosome 12 ◽  
Interphase Cells ◽  
Trisomy 12

Abstract Trisomy 12 is the most common cytogenetic abnormality in chronic lymphocytic leukemia (CLL), and a number of studies have suggested that it may be an adverse prognostic indicator. We have evaluated the usefulness of fluorescence in situ hybridization with a chromosome 12- specific probe as a simple means for detecting trisomy 12 in interphase cells. Forty cases of B-cell CLL previously studied with conventional cytogenetic techniques were analyzed with a biotinylated probe to the centromeric region of chromosome 12. Thirty of these retrospective cases could be reevaluated with in situ hybridization. Our analysis showed three hybridization signals (ie, trisomy 12) in interphase cells from seven of seven cases found previously to have trisomy 12. Trisomy 12 was also detected in five additional cases: in one case thought to have a normal karyotype, in two cases that had been inadequate for routine cytogenetic analysis, and in two cases that had been found to have an abnormal karyotype without trisomy 12. In a prospective series of 20 newly accrued CLL cases, all cases were analyzed successfully by in situ hybridization and six (30%) showed trisomy 12. We were able to perform the analysis on routinely prepared and previously Wright- stained peripheral blood smears. We conclude that fluorescence in situ hybridization is a simple means for the detection of trisomy 12 in CLL. The technique is more sensitive than conventional cytogenetic analysis and would be a useful tool in clinical studies.

scholarly journals Trisomy 12 in chronic lymphocytic leukemia detected by fluorescence in situ hybridization: analysis by stage, immunophenotype, and morphology

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 571-575 ◽  
Author(s):  
TH Que ◽  
JG Marco ◽  
J Ellis ◽  
E Matutes ◽  
VB Babapulle ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chronic Lymphocytic Leukemia ◽  
Fluorescence In Situ Hybridization ◽  
Clinical Stage ◽  
Lymphocytic Leukemia ◽  
Therapeutic Trial ◽  
Number Of Patients ◽  
Significant Difference ◽  
Trisomy 12

Abstract Fluorescence in situ hybridization (FISH) with a chromosome 12 specific alpha-centromeric probe was performed on interphase cells from 183 patients with B-cell chronic lymphocytic leukemia (CLL). Twenty one cases with trisomy 12 (11.5%) were detected. The number of trisomic cells ranged from 5.5% to 76% (mean 38.5%). No correlation was found between the presence of trisomy 12 and white blood cell count, hemoglobin level, platelet count, a specific immunophenotype, clinical stage, sex, splenomegaly, or lymphadenopathy. Morphologic review of all cases with trisomy 12 showed seven (33%) with more than 10% prolymphocytes and three (14%) with CLL of mixed cell type. While trisomy 12 is the most common chromosomal abnormality in CLL, it is more frequent in morphologically atypical cases, some of which may be undergoing transformation. There was a statistically significant difference in the incidence of atypical cases between those with (47%) and without (7.6%) trisomy 12 (P < .001). It remains to be determined whether this abnormality is associated with a worse prognosis; this is currently being investigated in the context of a national therapeutic trial. The technique used is more sensitive than conventional cytogenetic analysis, which in this series failed to detect trisomy 12 in six cases. FISH allows the systematic study on a large number of patients without the need of metaphase preparations.

Global DNA Hypermethylation in Chronic Lymphocytic Leukemia Correlates with Progressive Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5006-5006
Author(s):  
Margaret K. Yu ◽  
Aniko Szabo ◽  
Hector Bergonia ◽  
Anna Senina ◽  
John D. Phillips
Keyword(s):  
Dna Methylation ◽  
Chronic Lymphocytic Leukemia ◽  
Progressive Disease ◽  
Lymphocytic Leukemia ◽  
Global Dna Methylation ◽  
Dna Hypomethylation ◽  
Physician Visits ◽  
Mutational Status ◽  
Trisomy 12 ◽  
One Year

Abstract Global DNA hypomethylation is observed in chronic lymphocytic leukemia, but methylation has not been correlated with clinical outcome. Although patient survival correlates with factors such as the mutational status of the immunoglobulin variable genes, karyotype abnormalities, Zap-70, and CD38 expression, none of these predictors have altered the way clinicians practice. We report interim results in the assessment of global DNA methylation as a predictor of aggressive disease in patients with chronic lymphocytic leukemia. Fourteen patients with chronic lymphocytic leukemia donated blood samples for DNA studies at the same time as blooddraws for their physician visits. All the treatments occurred within one year and the follow-ups were at least within 12 months except for one patient. We thus classified patients into two groups: those who required treatment within one year and those who did not. The cutoff in methylation level providing the smallest observed prediction error was 4.125%; it correctly predicted 5/6 patients not needing treatment within a year and 5/6 patients needing treatment. These observed classification rates were adjusted for the bias resulting from the optimal selection of the cutoff using bootstrap. The adjusted sensitivity and specificity were 74% and 80%, respectively. Asymptomatic patients with chronic lymphocytic leukemia tended to have lower levels of global DNA methylation (median 3.5%) compared to symptomatic patients (median 4.5%). In other words, high levels of global DNA methylation were associated with higher disease burden, corresponding with higher lymphocyte and white blood cell numbers. Five patients without immediate need for cytoreductive therapy were enrolled on a pilot treatment trial with low-dose cladribine, by subcutaneous injection. Three out of the five patients have had a clinical response, a secondary endpoint. Two of the patients have achieved a partial response, as defined by the NCI sponsored working group, with at least a three month follow-up after discontinuation of the drug. Of the two patients with stable or progressive disease on cladribine, their global DNA methylation levels were higher, correlating with more chemotherapy resistant disease. DNA methylation Levels in Patients with Chronic Lymphocytic Leukemia Age Sex %5-MedC Zap-70 CD-38 Rai Stage FISH Req Treatment (mos) FISH= fluorescence in situ hybridization; Zap-70 assessed by immunochemistry 51 M 5.045 positive positive 4 Del13q14 0.75 73 F 4.865 positive not assessed 4 not assessed 12+ 52 F 4.665 positive negative 2 Del13q14 2 57 M 4.62 negative negative 4 Del13q14 2 66 M 4.59 positive not assessed 4 Del13q14 (5/05) and Del 17p and Del 13q14 (7/05) 0.25 67 M 4.14 positive positive 4 Trisomy 12 10 47 M 4.055 negative negative 0 not assessed 12+ 59 M 3.9 negative negative 2 46XY 0 72 M 3.54 negative not assessed 0 not assessed 8+ 64 M 3.55 positive not assessed 1 Del13q14 12+ 70 F 3.47 not assessed negative 4 Trisomy 12 12+ 68 F 3.47 positive negative 2 not assessed 12+ 77 M 3.2 not assessed not assessed 0 not assessed 12+ DNA Methylation Levels in patients with Chronic Lymphocytic Leukemia DNA Methylation Levels in patients with Chronic Lymphocytic Leukemia

Detection of Chromosomal Abnormalities in Chronic Lymphocytic Leukemia Increased by Interphase Fluorescence In Situ Hybridization in TPA-Stimulated Peripheral Blood Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4927-4927
Author(s):  
Anna Aventin ◽  
Jana Sanchez
Keyword(s):  
In Situ Hybridization ◽  
Chronic Lymphocytic Leukemia ◽  
Fluorescence In Situ Hybridization ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Chromosomal Abnormalities ◽  
Lymphocytic Leukemia ◽  
Peripheral Blood Cells ◽  
Trisomy 12

Abstract Chromosomal abnormalities, namely deletion 11q-,13q-, 17p- and trisomy 12, have prognostic significance for patients with chronic lymphocytic leukemia (CLL). Several studies have demonstrated that the interphase fluorescence in situ hybridization technique (I-FISH) in CLL identifies such genomic aberrations in a higher frequency than classical karyotyping, including stimulated cultures using B-cell specific mitogens. However, there appears to be no information in the literature comparing I-FISH on non-cultured and cultured cells in CLL. A total of 56 samples from 49 patients with CLL were studied using commercially available probes for chromosomes 11q22.3(ATM), 13q14(13S272), 17p13(p53) and 12 centromere(D12Z3). We compared the results obtained by I-FISH-PBMC and those by interphase fluorescence in situ hybridization on TPA-stimulated peripheral blood cells (I-FISH-TPA) used for conventional cytogenetics in order to evaluate the usefulness of I-FISH-TPA. The proportion of abnormal nuclei obtained with the I-FISH-TPA was higher than that found with I-FISH-PBMC (P<0.001). Consequently, 15 cases with a negative or borderline result by I-FISH-PBMC became positive by I-FISH-TPA for deletion 11q- (n=2), 13q- (n= 9) and trisomy 12 (n=4). In all but one of these, chromosomal abnormalities were reconfirmed by either metaphase-FISH or conventional G-banding. Disease detection thus increased from 51% with I-FISH-PBMC to 78% with I-FISH-TPA. Interestingly, all 15 cases which reached the diagnostic thresholds for deletion 11q-,13q- and trisomy 12 had a slight lymphocytosis. An absolute lymphocyte count <8.7×109/l was found to be the critical threshold (P=0.037) below which I-FISH-TPA should be performed rather than I-FISH-PBMC. We have shown that I-FISH-TPA can not only detect a higher proportion of abnormal interphase nuclei but can also identify abnormal CLL cases which may be overlooked by I-FISH-PBMC, especially those with low absolute lymphocyte counts. I-FISH-TPA is thus a reliable technique for clinical diagnostics in CLL.

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