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 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

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.

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.

scholarly journals Trisomy 12 in chronic lymphocytic leukemia: an interphase cytogenetic study

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 775-779
Author(s):  
AP Losada ◽  
M Wessman ◽  
M Tiainen ◽  
AH Hopman ◽  
HF Willard ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chronic Lymphocytic Leukemia ◽  
Karyotype Analysis ◽  
Cytogenetic Study ◽  
Normal Karyotype ◽  
Lymphocytic Leukemia ◽  
Metaphase Chromosomes ◽  
Interphase Cytogenetics ◽  
Trisomy 12

Interphase cytogenetics by means of in situ hybridization with the chromosome 12-specific biotinylated alpha satellite DNA probe pSP 12–1 was used for the study of trisomy 12, the most common chromosomal abnormality in chronic lymphocytic leukemia. In situ hybridization was performed on methanol/acetic acid fixed cells of conventional cytogenetic preparations from eight patients and on morphologically and immunologically classified cells of cytospin preparations from seven patients. The results show that trisomy 12 is more common than assumed on the basis of karyotype analysis of metaphase chromosomes: 2 of 13 patients with a normal karyotype in G-banding analysis were shown to have trisomy 12 by interphase cytogenetics. Immunophenotyping of the cells of one patient showed that the trisomy was restricted to cells with Ig light chain clonality. For the evaluation of the prognostic, therapeutic, and biologic significance of trisomy 12, in situ hybridization should be used in parallel with karyotype analysis because it allows the study of all cell populations of both interphase and mitotic cells, whether neoplastic or normal.

Chronic Lymphocytic Leukemia, Detection of Five Significant Prognostic Genomic Aberrations by Interphase Two-Color Fluorescence in Situ Hybridization Analyses: a Study of 24 Patients with Clinical Follow-up Ranged From 7 to 120 Months.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4716-4716
Author(s):  
Carlos Sergio Barragan ◽  
Silvia B. Hansson ◽  
Silvina A Cicchini ◽  
Monica Tamashiro ◽  
Pablo G Dinardo ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chronic Lymphocytic Leukemia ◽  
Fluorescence In Situ Hybridization ◽  
Lymphocytic Leukemia ◽  
The Other ◽  
Prognostic Information ◽  
Trisomy 12 ◽  
Genomic Aberrations

Abstract Abstract 4716 Background Conventional cytogenetic studies by chromosome banding are difficult in chronic lymphocytic leukemia (CLL) because of the low in vitro proliferation or mitotic activity of CLL cells. Interphase Fluorescence in situ hybridization (FISH) has improved the detection of genomic aberrations in CLL. We used this method to identify chromosomal abnormalities in patients with CLL at diagnosis, progression disease, after relapse or treatment failure. Methods Mononuclear cells from the blood of 24 Caucasian patients, 12 men and 12 women, age ranged from 39 to 84 years (median, 64) with CLL were analyzed by FISH, for deletions in chromosome bands 11q22.3, 6q23.3, 13q14.3, 17p13.1, and trisomy of chromosome 12. The patients stages were 0A:12; IA:1; IIA: 2; IIB:4; IIIA:1, IIIB:1; IIIC:1; IV:2. The follow up ranged was from 7 to 124 months. Results Chromosomal aberrations were detected in 15 of 24 (58.33 percent). The most frequent changes were a 12 trisomy (37.5 percent), a deletion in 11q23.3, (12.5 percent), a deletion in 6q23.3 (8.33 percent), a deletion in 17p13.1 ( 8.33 percent), a deletion in 13q14.3 8.33%. A patient showed four aberrations tri(12), d(17p13.1), d(6q23.3), d(11q23.3), she was resistant to Fludarabine + Cyclophosfamide treatment and Rituximab CHOP and had a survival of 51 months. The other patients with trisomy 12 alone are still alive and the survival were ranged from 7 to 120 month. Trisomy 12 was correlated with enlarged lymph nodes. Two patients undergo Richter transformation one of them with 6q23.3 the other without the aberrations assessed. The patients with deletion 11q23.3 were resistant to standard regimens treatment. Ten patients have stable disease (0A), clinical follow up ranged from 7 to 124 months; three with trisomy 12 the others without the genetic aberrations assesses. Longest survivals (124 month) were found in patients without aberration or with trisomy 12. Patients without aberrations or with trisomy 12 had similar evolution. A female patient, 84 years old state in stage 0A along 13 month with d(17p13.1), and d(11q23.3). Patients with 11q23.3 deletions had the shortest median treatment-free interval (11months), and those with trisomy 12 or deletion 13q14.3 had the longest (124 and 40 months respectively). Patients with 11q23.3 and 6q23.3 deletion had more advanced disease. Two patients died, both of them with 6q23.3, overall survival 51 and 54 months respectively. ZAP 70 and CD38 do not have correlation with presence of the genomic aberration assessed .The present of 11q23.3, 6q23.3, 17p13.1, age, the white-cell count, Rai - Binet stage and the serum lactate dehydrogenase level gave significant prognostic information. Conclusions Genomic aberrations are independent prognosis factors of disease progression and survival in Chronic lymphocytic leukemia; establish them properly will be an important goal standard, therefore incorporate FISH assay routinely could give significant prognostic information. These genetic findings are predictors of outcome treatment regimens and could help to choose the appropriated strategic treatments. Disclosures: No relevant conflicts of interest to declare.

Clinical, biological, and immunophenotypical characteristics of B-cell chronic lymphocytic leukemia with trisomy 12 by fluorescence in situ hybridization

Cytometry ◽  
1995 ◽  
Vol 22 (3) ◽  
pp. 217-222 ◽  
Author(s):  
Maria Dolores Tabernero ◽  
Jesus F. San Miguel ◽  
Juan Luis Garcia ◽  
Maria Garcia-Isidoro ◽  
Joop Wiegant ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Fluorescence In Situ Hybridization ◽  
Lymphocytic Leukemia ◽  
Trisomy 12 ◽  
Cell Chronic Lymphocytic Leukemia

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

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.

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