Cytogenetic studies in 77 patients with chronic lymphocytic leukemia: correlations with clinical, immunologic, and phenotypic data.

1984 ◽  
Vol 2 (10) ◽  
pp. 1121-1132 ◽  
Author(s):  
T Han ◽  
N Sadamori ◽  
H Ozer ◽  
R Gajera ◽  
G A Gomez ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Cytogenetic Study ◽  
Clonal Evolution ◽  
Clinical Stage ◽  
Normal Karyotype ◽  
Peripheral Blood Lymphocytes ◽  
Lymphocytic Leukemia ◽  
Stage Iii ◽  
Phenotypic Data ◽  
Trisomy 12

Cytogenetic analyses by G-banding and/or Q-banding techniques of polyclonal B cell mitogen-stimulated peripheral blood lymphocytes in 77 patients with chronic lymphocytic leukemia were carried out in the present study. Adequate metaphases were obtained in 65 patients (84%). Of 29 patients with abnormal karyotypes, ten (34%) had trisomy 12 as the sole abnormality, eight (28%) had trisomy 12 in combination with other karyotypic changes, and the remaining 11 had various karyotypic changes other than trisomy 12. There was a significant relationship between the abnormal karyotype and disease status, clinical stage, lymphocyte count, bone marrow infiltration pattern, monoclonal IgM gammopathy, and urinary monoclonal-free light chain status. Six of seven patients (87%) with trisomy 12 only had stage 0-11 disease, whereas all eight patients with trisomy 12 with other changes had stage III or IV disease (P less than .02). However, of nine patients with other karyotypic changes without trisomy 12, five had stage 0-II and four had stage III or IV disease. These observations suggest that trisomy 12 may be the primary or the earliest karyotypic change in a majority of aneuploid patients with chronic lymphocytic leukemia, and that other karyotypic changes in addition to trisomy 12 may develop as a result of clonal evolution, dedifferentiation, or therapy. Of nine patients in whom autopsy studies were carried out, four were found to have diffuse histiocytic lymphoma or Richter's syndrome (three with trisomy 12 in combination with other chromosome changes and one with normal karyotype). Our findings clearly demonstrate that cytogenetic study may be of value in the clinical and prognostic evaluation of patients with chronic lymphocytic leukemia.

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.

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

Abstract 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.

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.

Chronic lymphocytic leukemia: An Indian experience.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19007-e19007
Author(s):  
Ajay Gogia ◽  
Ritu Gupta ◽  
Atul Sharma ◽  
Lalit Kumar ◽  
Vinod Raina ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Early Stage ◽  
Indian Subcontinent ◽  
Clinical Stage ◽  
Lymphocytic Leukemia ◽  
Adverse Impact ◽  
Stage Iii ◽  
Total Leukocyte Count ◽  
Female Ratio ◽  
Free Survival

e19007 Background: Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder in the West accounting for about 30% of leukemias, whereas in Indian subcontinent it accounts for 3-5% of all leukemias. We aimed to evaluate biological and molecular prognostic parameters as well as therapeutic considerations in CLL patients in India. Methods: We retrospectively analyzed 510 patients with CLL, who presented at our institute over a period of 18 years. Results: The median age of CLL patients at presentation was 60 years (range: 28 - 92 years) with male: female ratio = 3:1. The median total leukocyte count was 45X109/L . As per clinical Rai stage distribution 55 (10.08%) patients were in Stage 0, 92 (18%) in stage I, 174 (34%) in stage II, 92 (18%) in stage III and 97 (19%) were in stage IV. ZAP-70 was positive ( > 20%) in 206 (57% , n = 361) , CD 38( > 30%) in 107 (29% , n = 363), and CD49d was positive ( > 30%) in 63 (50.3%, n = 127) cases. Beta-2 microglobulin (B2M) was elevated (≥3.5 mg/L) in 243 patients (70%, n = 347). One hundred and fifty six cases (57%, n = 273) were IGHV mutated and Del (17p) by FISH was observed in 18 cases (12%, n = 150). A total of 331 (64.9 %) patients required treatment wherein 155 patients (46.8%) received Chlorambucil-based, 110 ( 33.2%) received BR, 42 (12.6%) received Fludarabine based ( FC-7,FCR-35) and 41 patients received others regimen. Overall response rate seen with Chlorambucil, BR and Fludarabine based regimen was 67% ( CR-3.2%), 90% ( CR-45%) & 88% ( CR-44%) respectively. Median event free survival (EFS) and overall survival (OS) and was 3.5 years and 5.5 years respectively, with median follow up period of 3.9 years. Clinical stage (Rai III/IV), elevated B2 M, IGHV-unmutated had statistically significant adverse impact on OS and EFS. Fludarabine based chemotherapy appeared toxic as half of patients developed febrile neutropenia and various infections whereas in BR , cutaneous side effects were more common(p = 0.001) . In early stage CLL, median time to first treatment was 22 months and; IGHV-unmutated, elevated B2M and CD38 positivity were significantly associated with shorter treatment free survival. Conclusions: This is the largest series of CLL reported from Asia. Clinical Rai Stage III/IV, unmutated IGHV and elevated B2M have statistically significant adverse impact on survival of patients with CLL. BR was better tolerated than fludarabine based regimen with similar responses and events.

Trisomy 12 in Chronic Lymphocytic Leukemia and Hairy Cell Leukemia: A Cytogenetic and Interphase Cytogenetic Study

1994 ◽  
Vol 15 (1-2) ◽  
pp. 167-172 ◽  
Author(s):  
Antonio Cuneo ◽  
Renato Bigoni ◽  
Massimo Balboni ◽  
Maria Gretel Carli ◽  
Nadia Piva ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hairy Cell Leukemia ◽  
Cytogenetic Study ◽  
Lymphocytic Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Trisomy 12

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.

Recurrent Chromosome Abnormalities Define Non-Overlapping, Unique Subgroups of Tumors in Chronic Lymphocytic Leukemia Patients with Known Karyotypic Abnormalities

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4176-4176
Author(s):  
Victor H Jimenez-Zepeda ◽  
Wee Joo Chng ◽  
Esteban Braggio ◽  
Neil Kay ◽  
Jose Leis ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Chromosome Aberrations ◽  
Clustering Analysis ◽  
Clonal Evolution ◽  
Biological Evolution ◽  
Temporal Analysis ◽  
Median Number ◽  
Lymphocytic Leukemia ◽  
Trisomy 12 ◽  
Late Loss

Abstract Background B-cell chronic lymphocytic leukemia (B-CLL) is a well-defined clinical entity with heterogeneous molecular and cytogenetic features. Chromosome aberrations could be associated to specific CLL clinical features and outcomes and their impact on clonal evolution should have been addressed by using temporal analysis. In order to demonstrate the role of temporal analysis in CLL we conducted a comprehensive karyotypic survey of a large number of CLL cases with already known genetic aberrations to fully describe their meaning in terms of biological evolution. Methods A total of 1749 karyotypes were retrieved from the Mitelman Database of Chromosome Aberrations in Cancer. A matrix depicting the 360-band human chromosome ideogram was created. Regions that were either lost or gained in more than 3% of the cases were retained and identified as recurrent imbalances. Early and late imbalances were defined according to the appearance on the complex karyotypes. Descriptive statistics were used to summarize the genetic abnormalities. Results The median chromosome number and the median number of abnormalities per tumor (NAPT) were 46 and 1 respectively. (Figure 1 A and 1B) The most common abnormality seen was trisomy 12 which occurred in 29% (508 cases) followed by 13q14del (10.34%), 13q13del (6.63%) and add14q32 (6.63%). The temporal analysis revealed +12, 13q-, −17, 17p-, −Y and −X to be early imbalances (TO&lt;5), followed predominately by a late loss with TO=5–10.5 (11q-). Hierarchical clustering suggested there are different groups including: trisomy 12, 13q-, 11q-, and 6q-, which at least in this clustering analysis appeared to be mutually exclusive. In summary, we can conclude that overall CLL is a neoplasia that shows remarkable chromosome stability even when only abnormal karyotypes are evaluated. Interestingly, clustering analysis suggests there are non-overlapping, unique subsets of CLL cases where trisomy 12 is the most common and along with 13q-emerged as early events on CLL clonal evolution. Figure 1A. Chromosomes distribution in chronic Lymphocytes Leukemia karyotypes Figure 1A. Chromosomes distribution in chronic Lymphocytes Leukemia karyotypes Figure 1b. Chronic Lymphocytes Leukemia and Number of Abnormalities Per Tumor (NAPT) distribution Figure 1b. Chronic Lymphocytes Leukemia and Number of Abnormalities Per Tumor (NAPT) distribution Figure Figure

scholarly journals Karyotype-specific microRNA signature in chronic lymphocytic leukemia

Blood ◽  
2009 ◽  
Vol 114 (18) ◽  
pp. 3872-3879 ◽  
Author(s):  
Rosa Visone ◽  
Laura Z. Rassenti ◽  
Angelo Veronese ◽  
Cristian Taccioli ◽  
Stefan Costinean ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Chromosomal Abnormalities ◽  
Variable Region ◽  
Normal Karyotype ◽  
Lymphocytic Leukemia ◽  
High Expression ◽  
Mutation Status ◽  
Ighv Gene ◽  
Trisomy 12 ◽  
Disease Initiation

Abstract Chromosomal abnormalities, immunoglobulin heavy chain variable–region (IGHV) gene mutation status, and ζ-associated protein 70 (ZAP-70) expression levels have independent prognostic relevance in chronic lymphocytic leukemia (CLL); however, their concordance is variable. Because deregulation of microRNAs has been linked to disease initiation and progression in CLL, we studied the value of the microRNAs as a signature for CLL patients with specific chromosomal abnormalities. We identified 32 microRNAs able to discriminate the 11q deletion, 17p deletion, trisomy 12, 13q deletion, and normal karyotype cytogenetic subgroups. The expression values of 9 among the 32 microRNAs (miR-151-3p, miR-34a, miR-29c, miR-29b, miR-155, miR-148a, miR-146a, miR-146b5p, and miR-640) were correlated with gene expression data from the same samples to assess their biologic impact on CLL. In this study we also found that IGHV unmutated, high expression of ZAP-70 protein, and low expression of the miR-223, miR-29c, miR-29b, and miR-181 family were strongly associated with disease progression in CLL cases harboring 17p deletion, whereas in those harboring trisomy 12 only high expression of the miR-181a, among the analyzed parameters, suggested more aggressive disease. Thus, the use of the microRNA-based classifications may yield clinically useful biomarkers of tumor behavior in CLL.

scholarly journals Fluorescent in situ hybridization and cytogenetic studies of trisomy 12 in chronic lymphocytic leukemia

Blood ◽  
1993 ◽  
Vol 81 (10) ◽  
pp. 2702-2707 ◽  
Author(s):  
SM Escudier ◽  
JM Pereira-Leahy ◽  
JW Drach ◽  
HU Weier ◽  
AM Goodacre ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chronic Lymphocytic Leukemia ◽  
Median Survival ◽  
Chromosomal Abnormalities ◽  
Residual Disease ◽  
Clonal Evolution ◽  
Lymphocytic Leukemia ◽  
Cytogenetic Studies ◽  
Trisomy 12

Abstract Cytogenetic studies (CG) of 475 chronic lymphocytic leukemia (CLL) cases showed trisomy 12 in 6.1% or 26% of patients with abnormal karyotypes. Fluorescence in situ hybridization (FISH) detected trisomy 12 in 35% of 117 CLL patients. Only 34.6% of cases detected by FISH were detected by CG. Twelve patients had low levels of trisomic cells (4% to 11%) relative to clonal B cells (47.5% to 86%), suggestive of clonal evolution. Untreated patients with trisomy 12 were predominantly male (P < .05) and had an increased incidence of splenomegaly (P < .03). Patients with trisomy 12 were more likely to be previously treated and had advanced Binet stage compared with those without trisomy 12. The median survival was shorter in patients with trisomy 12 (7.8 years) and patients with other chromosomal abnormalities without trisomy 12 by FISH (5.5 years) than in patients with diploid karyotypes (14.4 years). The response to fludarabine was similar to that of patients with diploid karyotypes, but there was a trend for earlier disease progression. FISH detected residual disease in all patients with trisomy 12 in complete (n = 6) or partial remission (n = 4). As few as 1 trisomic cell in 5,000 was detected by performing FISH on fluorescence-activated cell sorter-sorted cells. Trisomy 12 was absent in T cells in patients with trisomy 12. We conclude that FISH identifies trisomy 12 approximately 2.6 times more often than CG, readily identifies minimal residual disease, and predicts for a shorter median survival.

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.

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