Centroblastic lymphoma of the thyroid supervening long-lasting chronic lymphocytic leukemia (B-CLL) demonstration of biclonality by Immunohistochemical and gene rearrangement analysis

1988 ◽  
Vol 66 (16) ◽  
pp. 736-742 ◽  
Author(s):  
L. Trümper ◽  
D. U. Matthaei-Maurer ◽  
W. Knauf ◽  
P. Möller
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Gene Rearrangement ◽  
Lymphocytic Leukemia ◽  
Centroblastic Lymphoma ◽  
Gene Rearrangement Analysis

scholarly journals Identical IGHV-D-J gene rearrangement may precede the clinical onset of chronic lymphocytic leukemia by several years

2010 ◽  
Vol 85 (11) ◽  
pp. 868-871 ◽  
Author(s):  
Maurizio Frezzato ◽  
Ilaria Giaretta ◽  
Domenico Madeo ◽  
Francesco Rodeghiero
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Gene Rearrangement ◽  
Lymphocytic Leukemia ◽  
Clinical Onset

scholarly journals Chronic lymphocytic leukemia presenting with ascites diagnosed by clonality analysis via gene rearrangement assay: A case report

2014 ◽  
Vol 7 (6) ◽  
pp. 1911-1914
Author(s):  
YEN-MIN HUANG ◽  
LEE-YUNG SHIH ◽  
PO DUNN ◽  
PO-NAN WANG ◽  
MING-CHUNG KUO ◽  
...  
Keyword(s):  
Case Report ◽  
Chronic Lymphocytic Leukemia ◽  
Gene Rearrangement ◽  
Lymphocytic Leukemia ◽  
Clonality Analysis

scholarly journals Phenotypic markers and BCL-1 gene rearrangements in B-cell chronic lymphocytic leukemia: a Cancer and Leukemia Group B study

Blood ◽  
1993 ◽  
Vol 82 (4) ◽  
pp. 1239-1246 ◽  
Author(s):  
RA Newman ◽  
B Peterson ◽  
FR Davey ◽  
C Brabyn ◽  
H Collins ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Gene Rearrangement ◽  
Surface Expression ◽  
Lymphocytic Leukemia ◽  
Aggressive Form ◽  
Younger Age ◽  
Group B ◽  
Leukemia Group ◽  
Activation Antigen

Abstract The markers, CD11b, CD11c, CD14, CD21, CD23, CD25, CD38, and FMC7 were correlated with morphologic and other laboratory and clinical characteristics of 127 patients with untreated CD5+ chronic lymphocytic leukemia (CLL). Only CD38 and CD21 were significantly associated with atypical CLL morphology. The integrin associated markers CD11b and CD11c were associated with lower leukocyte count (white blood cell count [WBC]) and lower Rai stage. By contrast, the activation antigen CD23 was associated with a higher WBC, higher Rai stage, younger age group, and the presence of lymphadenopathy. Therefore, we conclude that CD23 positivity may reflect a more aggressive form of CLL, and CD11b and CD11c positivity a less aggressive form. The BCL-1 gene rearrangement was present in 5 of 84 (6%) CLL cases examined and was associated with atypical morphology and surface expression of CD11b. Patients with a BCL-1 gene rearrangement may represent a CLL subset or possibly a different B-cell disease.

ZAP-70 Expression, VH-Mutation Status, Genomic Aberrations and Prognosis in Chronic Lymphocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1920-1920 ◽  
Author(s):  
Alexander Kröber ◽  
Dirk Kienle ◽  
Dirk Winkler ◽  
Andreas Bühler ◽  
Till Seiler ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Gene Rearrangement ◽  
Progressive Disease ◽  
Clinical Course ◽  
Surrogate Marker ◽  
Lymphocytic Leukemia ◽  
Mutation Status ◽  
Free Survival ◽  
Genomic Aberrations

Abstract The VH status is a strong prognostic marker in chronic lymphocytic leukemia (CLL). ZAP-70, a zeta associated tyrosine kinase physiologically expressed by T-cells, is overexpressed in VH unmutated CLL and could therefore serve as a surrogate marker for the VH status. We analyzed ZAP-70 expression (n=96), the VH status (n=75) and genomic aberrations (n=84) in a single center CLL cohort to study associations among these parameters and to assess their relative prognostic value. ZAP-70 expression was measured by 4-colour flow cytometry (CD5, CD19, CD3/56, ZAP-70) applying an unconjugated anti-ZAP-70-antibody (Upstate, clone 2F3.2) according to Crespo et al., NEJM 2003. ZAP-70 expression was positive (cut-off 20%) in 67% and negative in 33% of cases. VH was mutated in 33% and unmutated in 67% of cases. Unfavorable genomic aberrations (17p−, 11q−) were more frequently observed in cases with unmutated VH (46 vs. 9%) and in ZAP-70 positive cases (39 vs. 20%), while favorable genomic aberrations (13q− as single aberration) occurred more frequently in VH mutated (48 vs. 17%) and ZAP-70 negative subgroups (50 vs. 18%). ZAP-70 expression predicted the VH status in 84% of cases. At a median follow up time of 47 months (m), the median treatment free survival (TFS) of ZAP-70 positive and negative cases was 31 and 86 m (p=.057). The median TFS of the VH unmutated and VH mutated subgroups were 24 and 172 m (p<.001). Within the follow up time 10 deaths occurred. Of these, 8 cases exhibited high ZAP-70 expression and an unmutated VH, whereas 2 cases showed discordant results. Overall, discordant results for ZAP-70 expression and VH status were identified in 12 cases (ZAP-70 positive/VH mutated, 8 cases; ZAP-70 negative/VH unmutated, 4 cases). Of the 8 VH mutated cases with high ZAP-70 expression, only 1 case exhibited unfavorable genomic aberrations, 4 remained in stable disease, 4 developed progressive disease, 3 patients required therapy, and 1 of these 3 died within follow up time. Two of the 3 patients who required therapy, including the patient who died, showed a mutated V3-21 gene rearrangement, associated with an unfavorable outcome. Among the 4 cases with an unmutated VH and low ZAP-70 expression, 2 cases exhibited unfavorable genomic aberrations, 3 cases required therapy, 1 of these 3 died, and for one patient no clinical data were available. In summary, the imbalanced distribution of high risk genomic aberrations was similar when comparing the subgroups according to ZAP-70 expression and VH status. In our series an unmutated VH status predicted for shorter TFS, whereas high ZAP-70 expression did not reach significance. ZAP-70 expression was associated with unmutated VH, but a substantial number of cases showed discordant results for ZAP-70 expression and VH status. The pattern of genomic aberrations and the clinical course of the discordant cases were typical for their respective VH status. Compared to ZAP-70 expression the VH status appeared to be more informative in the prediction of the clinical course in our series of CLL patients.

The Incidence of Chronic Lymphocytic Leukemia in the General Population.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2809-2809
Author(s):  
Maurizio Frezzato ◽  
Alberto Tosetto ◽  
Ilaria Giaretta ◽  
Francesco Rodeghiero
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Gene Rearrangement ◽  
Epidemiological Data ◽  
Clinical History ◽  
Epidemiological Survey ◽  
Population Based ◽  
Lymphocytic Leukemia ◽  
Entire Cohort ◽  
Vh Gene

Abstract Background. Chronic Lymphocytic Leukemia is the most frequent leukemia in the Western countries (Rozman, 1995) but its incidence is not well established. Epidemiological data are based on reports from tumour registries, with an estimated incidence lower than 3-cases/100000 pts-year. Tumour registries can however underestimate the incidence of CLL as highlighted by the 37% higher incidence reported in a selected population of Veterans (Zent, 2000). We aimed to assessing the incidence of CLL in a population-based cohort from an epidemiological survey on familial thrombosis, (Tosetto, 2003) which was followed for at least 8 years. Material and Methods. 15109 healthy people from 18 to 65 years of age in the Vicenza township were enrolled in the VITA Project (8017 females and 7092 males, with a median age of 43 years). A clinical history was collected and blood and DNA samples were withdrawn and stored at the time of enrolment. The study begun in 1993 and ended in 1996. Patients with a diagnosis of CLL (ICD-9 code 204) were traced using data from the Veneto Region Health Service database, which records all hospital admission for residents in the enrolment area. Moreover, the database encompasses data of all the subjects visited in the Vicenza Hematology Department, the unique hematological facility of the area, even if not subsequently admitted to the hospital. Diagnosis of CLL was validated if based on morphological and immunophenotypic data according to currently accepted criteria (Cheson, 1988; IWCC, 1989; Rozman, 1995). Results. Six out 15109 people were diagnosed with a CLL (4 males). The median follow-up for the entire cohort was 8.2 years and the total time of exposure was 121000 pts-year. Incidence of CLL is estimated to be 4.9 cases/100000 pts-year (CI: 1.8–10.7). Diagnosis of CLL was done from 36 to 97 months after the enrolment. Mean age at diagnosis was 66 years (61 – 70). At the time of enrolment in the study, all of the patients had a normal WBC. Three persons presented an immunoglobulin VH gene rearrangement, 32, 54 and 57 months before diagnosis. All of the patients were asymptomatic at diagnosis. The median follow-up of all the subjects was 28 months (7 – 57 months). Only one of them became symptomatic and needed a treatment, 40 months after the diagnosis. Conclusions. According to our data, the incidence of CLL appears to be higher than assessed so far. In our opinion it’s noteworthy that the estimation is based on data of subjects evaluated in a clinical setting and not from tumour or disease registries. In fact it could be still underestimated comparing the young median age of our cohort with that usually reported at diagnosis (Rozman, 1995). Moreover, the comparison of our data with those available could suggest that only a quote of the cases might be usually diagnosed. Finally, the presence of the Ig VH gene rearrangement at the time of the enrolment suggests that the disease may be present a very long time before any clinical evidence.

scholarly journals Response assessment in chronic lymphocytic leukemia after fludarabine plus prednisone: clinical, pathologic, immunophenotypic, and molecular analysis [see comments]

Blood ◽  
1992 ◽  
Vol 80 (1) ◽  
pp. 29-36 ◽  
Author(s):  
LE Robertson ◽  
YO Huh ◽  
JJ Butler ◽  
WC Pugh ◽  
C Hirsch-Ginsberg ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Gene Rearrangement ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Time To Progression ◽  
Free Survival ◽  
Biopsy Examination ◽  
Gene Rearrangement Analysis

Abstract The goals of this study were to evaluate the response to treatment in chronic lymphocytic leukemia (CLL) according to clinical, pathologic, immunophenotypic, and molecular features, as well as to address the clinical significance of each finding. One hundred fifty-nine CLL patients with either advanced Rai stage III or IV (81 patients) or progressive Rai stage 0 to II (78 patients) were treated with fludarabine (30 mg/m2/d intravenously every day for 5 days) plus prednisone (30 mg/m2/d orally daily for 5 days). Thirty-six patients were previously untreated. The response rates were 12% complete response (CR), 30% nodular complete response (nCR), and 18% partial response (PR). In all patients who achieved a complete response (both CR and nCR) less than 30% of nucleated cells were lymphocytes on marrow aspirate differential analysis; however, nCR patients had residual nodular and/or interstitial lymphocyte involvement on marrow biopsy examination. There was no evidence of leukemic infiltration on marrow biopsy examination in CR patients. With a median follow-up of 35 months, comparison of time to progression in the CR and nCR groups at 2 years showed a projected 87% versus 55% progression-free survival (P less than .03). Residual disease assessment by flow cytometry using simultaneous dual-color staining on blood and marrow lymphocytes was also performed on each patient. Residual disease was determined by the expression of CD5 on B lymphocytes and the monoclonality of surface light-chain expression. After six courses of fludarabine plus prednisone, no residual disease was detected by flow cytometry in 89% of the CRs, 51% of the nCRs, and 19% of the PRs. Clinical residual disease in PR patients with no residual disease detectable by flow cytometry was limited to lymph-adenopathy. Time to progression at 2 years was longer in CR and nCR patients having no residual disease detected by flow cytometry (84% v 39% 2-year progression-free survival, P less than .001). Posttreatment lg gene rearrangement analysis using JH, J kappa, and C lambda probes demonstrated no rearranged bands and a return to the germline configuration in five of seven CRs and two of eight nCRs studied. The molecular studies were concordant with the dual- parameter immunophenotype results and none of the patients who reverted to a germline DNA pattern after treatment have experienced relapse. The absence of detectable minimal residual disease by bone marrow biopsy, dual-color flow cytometry, and lg gene rearrangement analysis is achieveable in CLL with fludarabine and is predictive of the response duration.

Chronic lymphocytic leukemia patients with a V1-69 gene rearrangement do not have inferior survival with respect to patients that express other unmutated VH genes

2007 ◽  
Vol 31 (2) ◽  
pp. 245-248 ◽  
Author(s):  
Irina Panovska-Stavridis ◽  
Martin Ivanovski ◽  
Nikola Siljanovski ◽  
Lidija Cevreska ◽  
Dimitar G. Efremov
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Gene Rearrangement ◽  
Lymphocytic Leukemia ◽  
Vh Genes

scholarly journals Response assessment in chronic lymphocytic leukemia after fludarabine plus prednisone: clinical, pathologic, immunophenotypic, and molecular analysis [see comments]

Blood ◽  
1992 ◽  
Vol 80 (1) ◽  
pp. 29-36 ◽  
Author(s):  
LE Robertson ◽  
YO Huh ◽  
JJ Butler ◽  
WC Pugh ◽  
C Hirsch-Ginsberg ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Gene Rearrangement ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Time To Progression ◽  
Free Survival ◽  
Biopsy Examination ◽  
Gene Rearrangement Analysis

The goals of this study were to evaluate the response to treatment in chronic lymphocytic leukemia (CLL) according to clinical, pathologic, immunophenotypic, and molecular features, as well as to address the clinical significance of each finding. One hundred fifty-nine CLL patients with either advanced Rai stage III or IV (81 patients) or progressive Rai stage 0 to II (78 patients) were treated with fludarabine (30 mg/m2/d intravenously every day for 5 days) plus prednisone (30 mg/m2/d orally daily for 5 days). Thirty-six patients were previously untreated. The response rates were 12% complete response (CR), 30% nodular complete response (nCR), and 18% partial response (PR). In all patients who achieved a complete response (both CR and nCR) less than 30% of nucleated cells were lymphocytes on marrow aspirate differential analysis; however, nCR patients had residual nodular and/or interstitial lymphocyte involvement on marrow biopsy examination. There was no evidence of leukemic infiltration on marrow biopsy examination in CR patients. With a median follow-up of 35 months, comparison of time to progression in the CR and nCR groups at 2 years showed a projected 87% versus 55% progression-free survival (P less than .03). Residual disease assessment by flow cytometry using simultaneous dual-color staining on blood and marrow lymphocytes was also performed on each patient. Residual disease was determined by the expression of CD5 on B lymphocytes and the monoclonality of surface light-chain expression. After six courses of fludarabine plus prednisone, no residual disease was detected by flow cytometry in 89% of the CRs, 51% of the nCRs, and 19% of the PRs. Clinical residual disease in PR patients with no residual disease detectable by flow cytometry was limited to lymph-adenopathy. Time to progression at 2 years was longer in CR and nCR patients having no residual disease detected by flow cytometry (84% v 39% 2-year progression-free survival, P less than .001). Posttreatment lg gene rearrangement analysis using JH, J kappa, and C lambda probes demonstrated no rearranged bands and a return to the germline configuration in five of seven CRs and two of eight nCRs studied. The molecular studies were concordant with the dual- parameter immunophenotype results and none of the patients who reverted to a germline DNA pattern after treatment have experienced relapse. The absence of detectable minimal residual disease by bone marrow biopsy, dual-color flow cytometry, and lg gene rearrangement analysis is achieveable in CLL with fludarabine and is predictive of the response duration.

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