Cytogenetic Profile of Lymphoma of Follicle Mantle Lineage: Correlation With Clinicobiologic Features

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1372-1380 ◽  
Author(s):  
Antonio Cuneo ◽  
Renato Bigoni ◽  
Gian Matteo Rigolin ◽  
Maria Grazia Roberti ◽  
Antonella Bardi ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Bone Marrow Involvement ◽  
Normal Karyotype ◽  
Chromosome Analysis ◽  
Prognostic Indicator ◽  
Lymph Node Involvement ◽  
Fish Analysis ◽  
Strong Impact ◽  
Trisomy 12 ◽  
Cytogenetic Profile

Abstract Conventional chromosome analysis (CCA) and interphase fluorescence in situ hybridization (FISH) was performed in 42 patients with mantle-cell lymphoma (MCL), with BCL1 rearrangement. The t(11;14)(q13;q32) or 11q abnormalities were detected by CCA in 34 cases, 20 of which had additional aberrations. A normal karyotype was observed in 8 cases. Probes detecting the chromosome aberrations that were observed in at least 3 cases by CCA, ie, +12, 13q14 deletion, and 17p deletion, were used for interphase FISH analysis. FISH detected total or partial +12, 13q14 deletion and 17p- in 28.5%, 52.4%, and 26% of the cases, respectively. The presence of these anomalies was not a function of karyotype complexity. Based on the results of CCA/FISH, three groups of increasing karyotype complexity were recognized: group 1, including 11 patients without detectable aberrations in addition to BCL1 rearrangement; group 2, including 14 patients with 1 to 2 additional anomalies; and group 3, including 17 patients with three or more additional anomalies. Clinical parameters associated with shorter survival were male sex (P= .006) and primary lymph-node involvement compared with primary bone marrow involvement (P = .015). Trisomy 12 was the only single cytogenetic parameter predictive of a poor prognosis (P = .006) and the best prognostic indicator was the derived measure of karyotype complexity (P < .0001), which maintained statistical significance in multivariate analysis (P< .0001). We arrived at the following conclusions: 13q14 deletion occurs at a high incidence in MCL; 17p deletion and total/partial +12 are relatively frequent events in MCL, the latter aberration being associated with a shorter survival; and the degree of karyotype complexity has a strong impact on prognosis in this neoplasia.

Cytogenetic Profile of Lymphoma of Follicle Mantle Lineage: Correlation With Clinicobiologic Features

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1372-1380 ◽  
Author(s):  
Antonio Cuneo ◽  
Renato Bigoni ◽  
Gian Matteo Rigolin ◽  
Maria Grazia Roberti ◽  
Antonella Bardi ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Bone Marrow Involvement ◽  
Normal Karyotype ◽  
Chromosome Analysis ◽  
Prognostic Indicator ◽  
Lymph Node Involvement ◽  
Fish Analysis ◽  
Strong Impact ◽  
Trisomy 12 ◽  
Cytogenetic Profile

Conventional chromosome analysis (CCA) and interphase fluorescence in situ hybridization (FISH) was performed in 42 patients with mantle-cell lymphoma (MCL), with BCL1 rearrangement. The t(11;14)(q13;q32) or 11q abnormalities were detected by CCA in 34 cases, 20 of which had additional aberrations. A normal karyotype was observed in 8 cases. Probes detecting the chromosome aberrations that were observed in at least 3 cases by CCA, ie, +12, 13q14 deletion, and 17p deletion, were used for interphase FISH analysis. FISH detected total or partial +12, 13q14 deletion and 17p- in 28.5%, 52.4%, and 26% of the cases, respectively. The presence of these anomalies was not a function of karyotype complexity. Based on the results of CCA/FISH, three groups of increasing karyotype complexity were recognized: group 1, including 11 patients without detectable aberrations in addition to BCL1 rearrangement; group 2, including 14 patients with 1 to 2 additional anomalies; and group 3, including 17 patients with three or more additional anomalies. Clinical parameters associated with shorter survival were male sex (P= .006) and primary lymph-node involvement compared with primary bone marrow involvement (P = .015). Trisomy 12 was the only single cytogenetic parameter predictive of a poor prognosis (P = .006) and the best prognostic indicator was the derived measure of karyotype complexity (P < .0001), which maintained statistical significance in multivariate analysis (P< .0001). We arrived at the following conclusions: 13q14 deletion occurs at a high incidence in MCL; 17p deletion and total/partial +12 are relatively frequent events in MCL, the latter aberration being associated with a shorter survival; and the degree of karyotype complexity has a strong impact on prognosis in this neoplasia.

Does supplemental interphase FISH analysis to standard chromosom analysis improve the detection of myelodysplastic syndrome?

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7060-7060 ◽  
Author(s):  
Benjamin Joseph Lang ◽  
Carol Minyon ◽  
Neelam Dhiman ◽  
Saurabh Gupta ◽  
Stella Wenceslao ◽  
...  
Keyword(s):  
Chromosomal Abnormalities ◽  
Statistical Significance ◽  
Chromosome Analysis ◽  
Diagnostic Value ◽  
Fish Analysis ◽  
Retrospective Data ◽  
Trisomy 8 ◽  
Prognostic Information ◽  
Monosomy 7 ◽  
Interphase Fish

7060 Background: Our objective was to evaluate whether the addition of interphase FISH analysis to standard chromosome analysis (CA) improves the detection of chromosomal abnormalities in patients with work up for myelodysplastic syndromes (MDS), acute myeloid leukemia, and myelodysplastic/myeloproliferative disorders and thereby increases diagnostic and prognostic information. We performed a retrospective data review of all MDS orders between January and September 2015 at our institution and evaluated concurrent tests for discrepancies between CA and FISH results. Our aim was to evaluate best practices with regard to diagnostic test utilization, specifically to assess the diagnostic and prognostic value of FISH in addition to CA for patients with potential and known MDS. Methods: Retrospective data review of concurrent test orders of CA and myelodysplastic FISH panel were reviewed. The myelodysplastic FISH panel consists of screening for monosomy 5/deletion 5q, monosomy 7/deletion 7q, CEP7, trisomy 8, and D20S108 (20q12). The results of CA and FISH results were analyzed using a chi-square test to evaluate statistical significance. Results: A total of 1121 samples were queried, of which 55 were excluded due to inability to perform CA and limited diagnostic value of accompanying standalone FISH data on the 4 markers tested in this study. Analysis of the eligible 1066 samples showed that the standalone CA had significantly higher sensitivity (p < 0.0001) in detecting abnormal cases (N = 247, 23.17%) as compared to standalone FISH analysis (N = 180, 16.89%). Overall, 173 (16.23%) cases were determined to be abnormal by both methods. CA correctly interpreted 1059 of 1066 cases (99.34%).Only 7 samples were interpreted as normal by CA but were found to be abnormal by FISH. This results in overall 0.66% (2.76% of the abnormal cases) of abnormalities that would have been missed by CA only. Conclusions: These findings suggest that FISH studies with 4 markers used in this study provide limited additional utility in cases with a complete CA.

B-Chronic Lymphocytic Leukemia (B-CLL), Small Lymphocytic Lymphoma (SLL) and Waldenstrom’s Macroglobulinemia (MW): A Comparative Fish Analysis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4801-4801
Author(s):  
Maria N. Dimopoulou ◽  
Maria K. Angelopoulou ◽  
Theodoros P. Vassilakopoulos ◽  
Marie-Christine Kyrtsonis ◽  
Dafni Koumbis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chromosomal Abnormalities ◽  
Absolute Lymphocyte Count ◽  
Mean Value ◽  
Lymphocytic Leukemia ◽  
Fish Analysis ◽  
Additional Tool ◽  
Trisomy 12 ◽  
Cytogenetic Profile ◽  
Lymphoplasmacytic Infiltration

Abstract Chromosomal abnormalities in B-CLL are considered as potent prognostic factors. In other small lymphocytic disorders, closely related to B-CLL, such as SLL and MW the cytogenetic profile has not been extensively studied. The purpose of the present study is to identify any potential differences in chromosomal abnormalities between B-CLL, SLL and MW. We studied 24 consecutive B-CLL, 13 SLL and 8 MW patients diagnosed in our Unit. Diagnosis was based on standard morphologic and immunophenotypic criteria for B-CLL and SLL patients. Cases with absolute lymphocyte count < 5x 109/L were considered as SLL. The diagnosis of MW was established in the presence of serum monoclonal IgM and lymphocytic/lymphoplasmacytic infiltration of the bone marrow. Separated lymphocytes from peripheral blood (B-CLL) or bone marrow (SLL and MW) were fixed and FISH analysis for trisomy 12 and 13q deletion was performed according to standard techniques. 200 intact interphase nuclei were scored for each sample. Cut-off levels were defined by the mean value plus 3 standard deviations of the frequency of the abnormalities in 10 normal controls. 5/24 B-CLL cases were positive for trisomy 12 (21%) versus 6/12 (50%) SLL and 0/7 (0%) MW cases. Del 13q was found in 8/14 (57%) of B-CLL, versus 1/6 (17%) of SLL and 0/8 (0%) of MW patients. We found a difference in the cytogenetic profile between B-CLL and SLL, which represent two closely related entities with different tissue localization pattern. Thus trisomy 12 was more frequently observed in SLL, whereas the opposite was true for del 13q. In addition none of these two chromosomal abnormalities was encountered in MW, a finding that could potentially serve as an additional tool for the differential diagnosis between these related disorders. These findings need to be confirmed in larger series of patients and their biologic significance should be further investigated.

Deletion 13q in B-CLL: Interphase FISH Reveals More 13q- Than Does CpG Stimulation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2070-2070
Author(s):  
Daniel L. Van Dyke ◽  
G.W. Dewald ◽  
T.G. Call ◽  
D.F. Jelinek ◽  
C.S. Zent ◽  
...  
Keyword(s):  
Normal Karyotype ◽  
Chromosome Analysis ◽  
High Risk Population ◽  
Fish Analysis ◽  
Balanced Translocation ◽  
Clonal Deletion ◽  
Chromosome 13 ◽  
Metaphase Cell ◽  
Interphase Fish ◽  
Normal Limits

Abstract The most common recognized cytogenetic change in B-CLL is a deletion involving band 13q14.3. Dewald found a heterozygous or homozygous 13q– in 92% of CLL patient samples using the FISH probe D13S319 that hybridizes to 13q14.3 (BJH 121:287, 2003). This contrasts with the usually normal conventional chromosome analysis (CCA) results partly because CLL cells divide infrequently but also because the 13q– is often visualized only by FISH (Stockero, Ca Genet Cytogenet 166:152, 2006). Mayr recently showed that CpG stimulation can reveal a chromosomally abnormal CLL clone in metaphase cells (Blood 107:742, 2006). The purpose of the present study was to compare the incidence of microdeletion and visible 13q deletion in CLL using interphase FISH and CCA after CpG culture on the same peripheral blood specimens. METHOD: We compared the chromosome 13 results by interphase FISH (fresh uncultured cells) and by a 20 metaphase CCA from 5–day CpG cultures. Our unselected CLL cohort (n=40) represented a typical and relatively high risk population: median age 61 (range 36–75), 48% CD38–positive, 62% ZAP–70 positive, and 48% IgVH unmutated. In addition 70% were previously treated for progressive disease, with all Rai stages represented. CpG RESULTS: By CCA of 40 patients, CpG stimulation revealed a clonal (multiple abnormal cells) or nonclonal (one abnormal cell) abnormal karyotype in 32 (80%) and a normal karyotype in 8 of the 40 patients (20%). Among the 32 abnormal cases, each chromosome 13 pair appeared normal in 17 and was abnormal in 15 (one was monosomy 13, 8 were 13q–, and 6 had a 13q translocation). CpG did not reveal a homozygous 13q abnormality in any patient. In total, CpG revealed a 13q abnormality in 15 of 40 (38%) patients (8 had multiple abnormal metaphases and 7 had only one abnormal metaphase). FISH RESULTS: By interphase FISH, 29 of 40 (73%) patients had a 13q–. The deletion was heterozygous in 18 patients, homozygous in 7, and mixed homo– and heterozygous in 4. Of the 18 with a heterozygous 13q loss by FISH, CpG revealed an abnormal 13 in only 8. Of the 11 patients with homozygous or mixed homo– and heterozygous 13q– by FISH, CpG revealed a heterozygous 13q abnormality in only 6. Of the 8 patients with a normal CpG karyotype, by FISH 5 had a 13q– in one or both 13s. Of the 9 patients with heterozygous 13q loss by CpG, the FISH result was 13q– in 4 and homozygous or mixed homo– and heterozygous 13q– in 5. Of the 6 with a chromosome 13 translocation by CpG, FISH revealed heterozygous 13q– in 4, mixed homo– and heterozygous 13q– in one, and in one case the 13q FISH result was within normal limits. In this latter case, CpG stimulation followed by metaphase FISH analysis confirmed that the apparently balanced translocation harbored a microdeletion 13q. Interphase FISH analysis confirmed the presence of a clonal deletion 13q in all 7 of the patients with a CpG metaphase result of a non-clonal (one metaphase cell) 13q abnormality. CONCLUSIONS: Even though CpG induces CLL metaphases in cell culture and reveals many chromosome abnormalities that cannot be identified by interphase FISH, cytogenetic evaluation of CLL by CpG alone significantly underestimates the incidence of 13q deletions. When a 20-cell analysis after CpG stimulation reveals a 13q abnromality in only one (apparently nonclonal) metaphase cell, concurrent interphase FISH analysis often confirms clonality for the 13q defect.

Spectral Karyotyping (SKY) ANALYSIS APPLIED to CHRONIC LYMPHOCYTIC LEUKEMIA CELLS Immunostimulated with the COMBINATION DSP30/IL-2.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4692-4692
Author(s):  
Fabio Morato Oliveira ◽  
Daniel Mazza Matos ◽  
Lorena Lobo Figueiredo-Pontes ◽  
Belinda Simoes ◽  
Eduardo M. Rego ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Chromosomal Abnormalities ◽  
Conflicts Of Interest ◽  
Calf Serum ◽  
Normal Karyotype ◽  
Lymphocytic Leukemia ◽  
Fish Analysis ◽  
Spectral Karyotyping ◽  
Cytogenetic Profile

Abstract Abstract 4692 Cytogenetic abnormalities play an important role as prognostic factors in CLL. The immunostimulatory oligonucleotide DSP30 in combination with IL-2 is an easy and efficient stimulus in metaphase generation for chromosomal banding. This technique allows a more comprehensive chromosome analysis compared to FISH. On the other hand, spectral karyotyping (SKY) analysis, a recent molecular cytogenetic tool for the screening of the entire genome, has been shown to provide additional chromosome information. By using a combination of molecular cytogenetics strategies, the goal of this investigation was to use the SKY to identify masked chromosomal abnormalities in CLL cells stimulated by the combination of DSP30 and IL-2. In addition we compared the cytogenetic profile obtained (DSP30/IL-2) with FISH analysis from unstimulated cells and ZAP70 expression for each patient. For metaphase induction, peripheral blood mononuclear cells were cultured in RPMI 1640 medium with 20% fetal calf serum in the presence of the immunostimulatory CpG-oligonucleotide DSP30 and IL-2. One extra set of cell culture without any stimulant agent for iFISH analysis was performed for each patient. The iFISH panel included probes for the detection of +12, and deletions of 11q22.3 (ATM), 13q14 (D13S25 and D13S319), and 17p13 (TP53). The cut off levels for trissomy 12 (>2%), del(13q) (>2.4%), del(11q23.3) (>.5%), del(17p13.1) (>3%) were established according to the iFISH patterns observed in a group of 4 age and sex-matched normal control peripheral blood samples studied with the same probes. Spectral karyotype analysis (SKY) was performed, according manufactures' instruction, in all patients. The ZAP70 expression was determined by flow cytometry analysis and the cut off value was 20%. In a group of 35 subjects studied, the cytogenetic analysis with DSP30/IL-2 showed chromosomal aberrations in 27. The following abnormalities were observed: +4, +5, +8(x2), +11, +12, +15(x2), -17, +18, +19, +21, del(6)(q24), del(11)(q13∼q23), del(12)(p13), del(13)(q31), del(14)(q24), del(17)(p13), t(1;12)(q31;p13), t(11;13)(q23;q12), t(15;18)(q11.1;q11), t(1;10)(p22;p14), t(14;22)(q32;q11), t(17;18)(q10;q10), t(9;13)(q21;q22), t(10;13)(q26;q14), t(9;12)(q12;p11), t(X;12)(p11.2;q24). Eight patients exhibited normal karyotype. The SKY analysis confirmed the abnormalities previously seen by G-banding (DSP30/IL-2), however, did not identify any new abnormality in subjects with normal karyotype. The iFISH analysis agreed with the cytogenetic profile obtained with DSP30/IL-2. The ZAP70 expression did not show any relationship between the group of patients with chromosomal abnormalities and the group with normal karyotype. The use of the immunostimulatory oligonucleotide DSP30 in combination with IL-2 showed to be effective to induce cell cycle progression of CLL. Cytogenetic aberrations detected by G-banding in addition to FISH were heterogeneous. The limited panel used for iFISH analysis may contribute to underestimate the prognostic value, since others abnormalities may be present in patient's karyotype. In conclusion, SKY analysis did not reveal any masked abnormality beyond those showed by G-banding resolution. These results indicate that G-banding analysis (DSP30/IL-2) can contribute to the stratification of different subsets of CLL patients with complex karyotype associated with poor prognosis. Disclosures: No relevant conflicts of interest to declare.

Retreatment with Alemtuzumab after a First, Successful Alemtuzumab Treatment in B-CLL.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4714-4714 ◽  
Author(s):  
Michael Fiegl ◽  
Florian Falkner ◽  
Andreas Falkner ◽  
Niklas Zojer ◽  
Michael Fridrik ◽  
...  
Keyword(s):  
Survival Rates ◽  
Normal Karyotype ◽  
Early Death ◽  
Complete Response ◽  
Median Number ◽  
Time Interval ◽  
Heavily Pretreated ◽  
Trisomy 12 ◽  
Risk Patients ◽  
Cytogenetic Profile

Abstract Alemtuzumab is the standard therapy for treatment of patients with relapsed/refractory B-CLL, and significant responses have also been documented in the front-line CLL setting. We and others have demonstrated, in controlled studies and retrospective surveys, that heavily pretreated patients who achieve a complete response (CR) or partial response (PR), or even stable disease (SD), as defined by the National Cancer Institute (NCI) criteria, benefit in terms of quality of life and prolonged overall survival (OS). This is probably due to the fact that response is of long duration and that, in many cases, effective re-treatment is feasible. We analysed which treatments were used following a first course of alemtuzumab in CLL (Fiegl et al. Cancer2006;107:2408–16), and found that alemtuzumab, alone or in combination, was the most frequently used drug for re-treatment. Here we present updated data in 26 CLL patients re-treated with alemtuzumab. Seventeen patients were male (65%), had B-CLL (n=23), B-CLL with more than 15% prolymphocytes (n=2), or CLL with Richter’s transformation (n=1). The median number of previous therapies including the first course of alemtuzumab was 4 (range, 2–12), and 15 cases (58%) were fludarabine-refractory. At the start of re-treatment, the majority of patients had Rai stage 4 disease. Fluorescence in situ hybridization (FISH) cytogenetics according to Dohner’s classification were available in 13 patients, and 5 patients had a high risk anomaly (17p deletion). The median time interval between last dose of alemtuzumab and start of alemtuzumab re-treatment was 10.2 months (1.7–28.3 months). Response evaluation according to NCI criteria was available in 17 patients. Alemtuzumab re-treated patients had PR, SD, and progressive disease (PD) rates of 53%, 18%, and 18%, respectively. In 12% response could not be evaluated because of early death. Survival rates were available for all 26 patients. The median OS since start of alemtuzumab re-treatment was 16.7 months. This favourable survival time underscores the fact that patients receiving alemtuzumab re-treatment are selected because they benefited from the previous course of alemtuzumab. There was a dramatic difference in outcome depending on whether alemtuzumab re-treatment was necessary earlier or later: median OS was 8.4 months in patients who had to be re-treated within 10.3 months after last dose of initial course of alemtuzumab, whereas median OS was not reached in patients retreated after a longer interval (P=0.001). OS was inferior in cytogenetically poor risk patients (17.8 months in 17p-deleted patients vs. “not reached” in patients with 13q deletion, trisomy 12, or normal karyotype; P=0.01). There was no difference in OS in fludarabine-refractory patients. Re-treatment was well tolerated, with moderate toxicity. In conclusion, we hereby demonstrate that B-CLL patients who have been treated successfully with alemtuzumab may benefit profoundly from a second course of alemtuzumab, especially if there is a prolonged interval between the treatments, and a favourable cytogenetic profile is present.

Clinical Significance of 13q14 Number of Deleted Cells in Chronic Lymphocytic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4581-4581
Author(s):  
Giovanni Del Poeta ◽  
Francesca Maria Rossi ◽  
Maria Ilaria Del Principe ◽  
Michele Dal Bo ◽  
Annalisa Biagi ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Conflicts Of Interest ◽  
Normal Karyotype ◽  
Progression Free Survival ◽  
Intermediate Stage ◽  
Lymphocytic Leukemia ◽  
Prognostic Indicators ◽  
Fish Analysis ◽  
Clinical Difference ◽  
Trisomy 12

Abstract Abstract 4581 Cytogenetic aberrations are considered major prognostic indicators for predicting the survival of chronic lymphocytic leukemia (CLL) patients (Dohner et al, 2000) and interphase fluorescent in situ hybridization (I-FISH) with specific probes is generally used to detect the most frequent abnormalities. Moreover, deletion 13q14.3 on FISH analysis which is the most common cytogenetic abnormality in CLL is a favorable prognostic biomarker when detected as a sole abnormality, even if a higher percentage of 13q- nuclei was found to be associated with significantly shorter time to treatment (P<0.001), (van Dike et al, 2010; Dal Bo et al, 2011). Therefore, the primary endpoints of our research were: 1) to determine progression free survival (PFS) and overall survival (OS) on the basis of percentages of 13q- nuclei and 2) to confirm 13q14 number of deleted cells as an independent prognostic factor. We investigated 503 pts, median age 65 years (range 33–89), 291 males and 212 females. With regard to modified Rai stages at diagnosis, 163 had a low stage, 320 an intermediate stage and 20 a high stage. Probes for chromosome 13q (LSI-D13S319), 11q (LSI-ATM), 17p (LSI-p53) and chromosome 12 (CEP12) were used on nuclei collected at diagnosis. One hundred fifty-three patients (30.4%) exhibit a normal karyotype, 203 pts (40.4%) showed an isolated 13q-, 63 pts (12.5%) presented trisomy 12, 49 pts (9.7%) 11q deletion, 26 (5.2%) 17p deletion and 9 (1.8%) other chromosome abnormalities. Clearly, patients with intermediate/poor cytogenetic abnormalities (trisomy 12, del11q-, del17p-) showed significant shorter PFS and OS (7% vs 36% at 14 years and 45% vs 77% at 14 years, P<0.0001) in comparison with normal or del13q- pts. Maximally selected log-rank statistics identified the 50% of nuclei bearing del13S319 as the most appropriate cut-off value capable of separating del13q- cases into two subgroups with different PFS and OS distributions. In fact, pts with isolated 13q- in <50% of nuclei (110 pts) showed a longer PFS and OS (62% vs 16% at 12 years, P<0.0001 and 95% vs 47% at 16 years, P=0.0007, Figure) compared to those with ≥50% of nuclei (93 pts). Noteworthy, 64 (69%) of 93 of 13q- >50% pts had received chemotherapy at the time of analysis, whereas only 27 (25%) of 110 of 13q- <50% pts had been treated (P <0.0001). There was no significant clinical difference between heterozygous and homozygous 13q- patients as well as between 13q- cases with RB1 deletion (delRB1) and 13q- without delRB1. There was a significant correlation between number of 13q deleted nuclei and number of B-lymphocytes/microliter (P<0.0001) at diagnosis as well as between 13q- nuclei percentages and lymphocyte doubling time (P=0.001), meaning that 13q- nuclei represent both the amount of disease and the proliferation rate in CLL. Only slight significant correlations were found between 13q- percentages and CD38 (P=0.04) or ZAP-70 (P=0.01) or IgHV status (P=0.03), whereas 36 of 54 (67%) CD69+ pts had del13q- >50% (P=0.0003). In the context of del13q- subset, multivariate analysis of PFS confirmed the percentage of nuclei (P=0.00007) together with IgHV status (P=0.003) and ZAP-70 (P=0.0002) as an independent prognosticator. With regard to OS, percentage of nuclei (P=0.02) together with age (P=0.009) and IgHV status (P=0.03) was again confirmed as an independent variable. Therefore, the percentage of nuclei exhibiting 13q- at diagnosis has to be considered an important predictor of the clinical outcome and the clinical implications of an isolated 13q deletion in CLL appear more complex and important than originally considerated. Disclosures: No relevant conflicts of interest to declare.

Immunophenotyping and cytogenetic profile of children with acute lymphoblastic leukemia: A study from a tertiary care center from Kashmir.

JMS SKIMS ◽  
2020 ◽  
Vol 23 (2) ◽  
Author(s):  
Faisal R Guru ◽  
Nisar Ahmad Syed ◽  
Shumail Bashir ◽  
Sanudev Sadanandan Vp ◽  
Hashim Kunju Ismail ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cytogenetic Study ◽  
Lymphoblastic Leukemia ◽  
Tertiary Care ◽  
Medical Science ◽  
Fish Analysis ◽  
Jammu And Kashmir ◽  
Mll Gene ◽  
Cytogenetic Profile ◽  
Study Participants

Background The complete cytogenetic and immunophenotyping data in children suffering from acute lymphoblastic leukemia (ALL) in Jammu and Kashmir is scarce. To bridge this knowledge gap the present study proposes to evaluate the immunophenotype and cytogenetic profile of pediatric ALL patients treated in our hospital. Material and methods This hospital-based observational study was conducted on 180 pediatric patients aged between 1  to 18 years who had visited the Paediatric unit of the  Department of Medical Oncology at Sher-I -Kashmir Institute of Medical Science, Srinagar ,Jammu and Kashmir between the January 2015 to December 2019. Result Among the study participants, 57.8% were male and 42.2% were female with a mean age of 9.24 years and median of 8 Years. Among the participants, 57.2% were below 10 years of age and 42.8% were above 10years of age. CNS disease was reported in 7.8%  of the study participants.  63.3% patients  had a TLC count of less than 20000. Immunophenotyping data revealed pre-B ALL in 77.8% of children. Cytogenetic study was conducted on 153 patients among them 74.4% had a normal karyotype, 7.2% s had hyperdiploidy and 3.3% had hypodiploidy. The FISH analysis showed that 23.3% of study participants were positive for the TEL-AML study, 11.1% were positive for BCR-ABL analysis and 4.4% of participants were positive for MLL gene analysis. The overall survival in the study population was 78.9% among the study participants. Only the MLL gene rearrangement analysis showed a statistically significant correlation with the survival analysis (P<0.5). Conclusion In summary, the present study reported the complete cytogenetic and immunophenotyping profile of the children suffering from acute lymphoblastic leukemia in Jammu and Kashmir.

THE ROLE OF THE GENETIC ABNORMALITIES, EPIGENETIC AND microRNA IN THE PROGNOSIS OF CHRONIC LYMPHOCYTIC LEUKEMIA

2018 ◽  
Vol 40 (4) ◽  
pp. 261-267 ◽  
Author(s):  
K Tari ◽  
Z Shamsi ◽  
H Reza Ghafari ◽  
A Atashi ◽  
M Shahjahani ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Kinase Inhibitors ◽  
Bone Marrow Involvement ◽  
P53 Mutation ◽  
Lymphocytic Leukemia ◽  
Gene Promoters ◽  
Epigenetic Changes ◽  
Genetic Changes ◽  
Trisomy 12

Chronic lymphocytic leukemia (CLL) is increased proliferation of B-cells with peripheral blood and bone marrow involvement, which is usually observed in older people. Genetic mutations, epigenetic changes and miRs play a role in CLL pathogenesis. Del 11q, del l17q, del 6q, trisomy 12, p53 and IgVH mutations are the most important genetic changes in CLL. Deletion of miR-15a and miR-16a can increase bcl2 gene expression, miR-29 and miR-181 deletions decrease the expression of TCL1, and miR-146a deletion prevents tumor metastasis. Epigenetic changes such as hypo- and hypermethylation, ubiquitination, hypo- and hyperacetylation of gene promoters involved in CLL pathogenesis can also play a role in CLL. Expression of CD38 and ZAP70, presence or absence of mutation in IgVH and P53 mutation are among the factors involved in CLL prognosis. Use of monoclonal antibodies against surface markers of B-cells like anti-CD20 as well as tyrosine kinase inhibitors are the most important therapeutic approaches for CLL.

P–575 Patients with recurrent implantation failures (RIF): chromosome abnormalities in the resulting embryos

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C Albanese ◽  
D Perruzza ◽  
C Tabanelli ◽  
S Sgargi ◽  
M C Magli ◽  
...  
Keyword(s):  
Live Birth ◽  
Uterine Cavity ◽  
Implantation Rate ◽  
Normal Karyotype ◽  
Great Majority ◽  
Chromosome Analysis ◽  
Delivery Rate ◽  
Comparative Genomic ◽  
Male Factor ◽  
Preimplantation Genetic Testing

Abstract Study question Do RIF patients have the preimplantation genetic testing for aneuploidy (PGT-A) overcome their infertility condition? Summary answer PGT-A positively impact on implantation rate in RIF patients What is known already The most common definition of RIF is failure to achieve a pregnancy after three consecutive transfers of good quality embryos. This term possibly represents a heterogeneous category of infertile couples as the causes of repeated failures can be diverse. Especially intriguing is the case of patients with an age lower than 39 years for which the oocyte quality is expected not to be compromised by the well known age effect on female fertility. The chromosome analysis of the resulting embryos has been proposed as a valid method to improve implantation in the great majority of RIF patients Study design, size, duration This retrospective study included 49 patients with at least three previous consecutive implantation failures, which underwent PGT-A from January 2016 to April 2020. Both partners had a normal karyotype. Only patients with a female age below 39 years were included, who presented with a normal uterine cavity. Couples with a severe male factor were excluded. Single frozen blastocysts were transferred according to chromosomal results Participants/materials, setting, methods Maternal age was 35.5 ± 3.1 years. All blastocysts were vitrified after trophectoderm biopsy. Whole genome amplification and array comparative genomic hybridization were performed on biopsies. Only euploid embryos were transferred. The primary outcome was the live-birth delivery rate after the first transfer Main results and the role of chance Before starting a PGT-A cycle, these patients underwent 213 embryo transfers with 251 embryos replaced. A total of 264 blastocysts were analyzed, 140 of which were aneuploid (53%). Monosomy or trisomy was reported in 67 of the diagnosed samples (67/140, 48%) whereas the remaining 73 carried complex aneuploidies (73/140, 52%). The remaining 124 blastocysts (47%) were diagnosed as euploid. All patients performed an embryo transfer resulting in 28 clinical pregnancies (57%). There were 5 spontaneous abortions and the live-birth delivery rate per patient was 47% Limitations, reasons for caution This study suffers from the weakness related to retrospectivity. In addition, as euploid embryos are still cryopreserved, the delivery rate could change at completion of the cycles Wider implications of the findings: A RIF condition can be attributed, at least in a good proportion of cases, to the generation of high percentages of aneuploid embryos. In this case, the transfer of euploid blastocysts has high chances to classify this category of RIF patients has having an embryonic cause of infertilit. Trial registration number Not applicable

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