scholarly journals Isochromosome 17q in Chronic Lymphocytic Leukemia

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Eyad Alhourani ◽  
Martina Rincic ◽  
Joana B. Melo ◽  
Isabel M. Carreira ◽  
Anita Glaser ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Prognostic Marker ◽  
Chromosomal Aberrations ◽  
Poor Prognosis ◽  
Lymphocytic Leukemia ◽  
Response To Treatment ◽  
Cytogenetic Abnormalities ◽  
Follow Up Studies

In chronic lymphocytic leukemia (CLL), presence of acquired cytogenetic abnormalities may help to estimate prognosis. However, deletion of TP53 gene, which is associated with an aggressive course of the disease and poor prognosis along with a lack of response to treatment, is one of the alterations which may escape cytogenetic diagnoses in CLL. Thus, other techniques have emerged such as interphase fluorescence in situ hybridization (iFISH). Deletion of TP53 may but must not go together with the formation of an isochromosome i(17q); surprisingly this subgroup of patients was not in the focus of CLL studies yet. This study was about if presence of i(17q) could be indicative for a new subgroup in CLL with more adverse prognosis. As a result, TP53 deletion was detected in 18 out of 150 (12%) here studied CLL cases. Six of those cases (~33%) had the TP53 deletion accompanied by an i(17q). Interestingly, the cases with i(17q) showed a tendency towards more associated chromosomal aberrations. These findings may be the bases for follow-up studies in CLL patients with TP53 deletion with and without i(17q); it may be suggested that the i(17q) presents an even more adverse prognostic marker than TP53 deletion alone.

MDR-1, but notMDR-3gene expression, is associated with unmutated IgVHgenes and poor prognosis chromosomal aberrations in chronic lymphocytic leukemia

2006 ◽  
Vol 47 (11) ◽  
pp. 2308-2313 ◽  
Author(s):  
Christine Matthews ◽  
Mark A. Catherwood ◽  
Anne-Marie Larkin ◽  
Martin Clynes ◽  
Tcm ‘Curly’ Morris ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Chromosomal Aberrations ◽  
Poor Prognosis ◽  
Lymphocytic Leukemia ◽  
Mdr 1

scholarly journals Chromosomal aberrations detected by Fluorescence in situ hybridization in 344 Brazilian chronic lymphocytic leukemia patients

2017 ◽  
Vol 39 (4) ◽  
pp. 388-390
Author(s):  
Maria Eduarda Sanseverino de Lourenço da Motta Zorovich ◽  
Denise Albuquerque Dourado ◽  
Maria de Lourdes Lopes Ferrari Chauffaille
Keyword(s):  
In Situ Hybridization ◽  
Chronic Lymphocytic Leukemia ◽  
Fluorescence In Situ Hybridization ◽  
Chromosomal Aberrations ◽  
Lymphocytic Leukemia

Predicting clinical outcome in CLL: how and why

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 421-429 ◽  
Author(s):  
Tait D. Shanafelt
Keyword(s):  
Lymphocytic Leukemia ◽  
Response To Treatment ◽  
Patient Counseling ◽  
Patient Risk ◽  
Disease Biology ◽  
Ighv Gene ◽  
Integrated Risk ◽  
Stratification System

Abstract The clinical course of patients with chronic lymphocytic leukemia (CLL) is heterogeneous, with some patients experiencing rapid disease progression and others living for decades without requiring treatment. Clinical features and molecular/biologic factors such as ZAP-70, immunoglobulin heavy chain (IGHV) gene mutation status, and cytogenetic abnormalities on fluorescent in situ hybridization (FISH) have been found to be robust predictors of treatment-free survival and overall survival among newly diagnosed patients. Beyond their widely recognized value for providing insight into disease biology and utility for stratifying patient risk in clinical trials, these prognostic tools play an important role in the current counseling and management of patients with CLL. Recent studies have focused on how to combine the results of multiple prognostic assays into an integrated risk stratification system and explored how these characteristics influence response to treatment. This chapter reviews the available tools to stratify patient risk and discusses how these tools can be used in routine clinical practice to individualize patient counseling, guide the frequency of follow-up, and inform treatment selection.

scholarly journals Fluorescent in situ hybridization in patients with chronic lymphocytic leukemia with autoimmune hemolytic anemia

2020 ◽  
pp. 16-16
Author(s):  
M.O. Valchuk ◽  
O.V. Zotova ◽  
A.S. Lukyanova ◽  
O.Ya. Vyhovska ◽  
Yu.S. Karo ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chronic Lymphocytic Leukemia ◽  
Autoimmune Hemolytic Anemia ◽  
Fluorescent In Situ Hybridization ◽  
Tp53 Gene ◽  
Lymphocytic Leukemia ◽  
Response To Treatment ◽  
Cytogenetic Changes ◽  
Atm Gene

Background. Gene aberrations are an important prognostic criterion for the course of B-cell chronic lymphocytic leukemia (B-CLL) and response to treatment, which includes not only immunochemotherapy, but also concomitant infusion therapy for the prevention and correction of complications. Objective. To investigate the presence of prognostic cytogenetic changes in patients with B-CLL with autoimmune hemolytic anemia (AIGA). To analyze the course of the disease and the direct effect of treatment in patients with cytogenetic changes of different nature. Materials and methods. Cytogenetic studies were performed by fluorescent in situ hybridization (FISH) on the interphase nuclei of peripheral blood lymphocytes in 11 patients with B-CLL with AIGA. Probes to the ATM genes (gene localized in region 11q23) and TP53 (gene localized in region 17p13) were used in the work, the deletions of which have prognostic value in B-CLL. All patients received treatment. Results. Among 11 patients with AIGA, signals to both genes were detected in nuclei 4. No deletions were detected. In the cells of the other 7 patients, the absence of a single signal to the ATM gene was detected, indicating the presence of a deletion of del(11)(q23). In recent patients, an unfavorable course of B-CLL disease was observed without response to treatment. Deletions of the TP53 gene in patients of the studied group were not detected. Conclusions. FISH study in patients with B-CLL with AIGA revealed the presence of important and prognostically unfavorable chromosomal rearrangement of the ATM gene in 63 % of patients.

MicroRNA-29c and 223 Are Powerful Prognostic Factors for Chronic Lymphocytic Leukemia and Improve Risk Stratification When Combined with ZAP70 and LPL in a qPCR Score.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1066-1066
Author(s):  
Basile Stamatopoulos ◽  
Nathalie Meuleman ◽  
Dominique Bron ◽  
Benjamin Haibe-Kains ◽  
Pascale Saussoy ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
Lymphocytic Leukemia ◽  
Early Therapy ◽  
Mutational Status ◽  
Igvh Mutational Status ◽  
Binet Stage

Abstract Background: MicroRNAs (or miR) are a novel class of small noncoding RNA involved in gene regulation. Aberrant microRNA expression has been recently associated with chronic lymphocytic leukemia (CLL) outcome. Currently, the heterogeneous evolution of this disease can be predicted by several prognostic factors. Nevertheless, a better individualization of the outcome in a given patient is still of utmost interest. Methods: In the current study, we investigated the expression of two microRNAs, miR-29c and miR-223, compared them to other biological or clinical markers and proposed a quantitative real-time PCR (qPCR) score to better assess CLL outcome. All cut-offs were calculated by ROC curve analysis maximising the correlation with the immunoglobulin variable heavy chain (IgVH) mutational status; statistical differences were evaluated by Mann Whitney test or Kruskal-Wallis test ; treatment-free (TFS) and overall (OS) survival differences were investigated by log-rank test or Cox proportional hazard ratio (HR). Results: miR-29c and miR-223 expression decreased significantly with progression along Binet Stage A to C (P=0.0010 and P=0.0183, respectively), and were significantly lower in poor prognosis subgroups defined by cytogenetic abnormalities, IgVH mutational status, lymphocyte doubling time, solubleCD23, β2-microglobulin, ζ-associated protein 70 (ZAP70), lipoprotein lipase (LPL) and CD38 expression. Furthermore, miR-29c and miR-223 could predict TFS (n=110, P=0.0015 and P<0.0001, respectively) and OS (n=110, P=0.0234 and P=0.0008, respectively). Regarding all these results, we developed a qPCR score (from 0 to 4 poor prognostic markers) combining miR-29c, miR-223, ZAP70 and LPL in order to stratify treatment and death risk in a 110 patient cohort with a median follow-up of 72 months (range, 2–312). Patients with a score of 0/4, 1/4, 2/4, 3/4, and 4/4 had a median TFS of >312, 129, 80, 36 and 19 months, respectively (HR=17.00, P<0.0001). Patient with a score of 0–1/4, 2–3/4 and 4/4 had a median OS of >312, 183 and 106 months, respectively (HR=13.69, P=0.0001). Interestingly, during the first 50 months after diagnosis, only 10% of patients with a 0/4 score required a treatment, when compared to 100% of the 4/4. Furthermore, during the total follow-up (312 months), patients with a 4/4 score had a 27-fold higher risk to be treated and a 31-fold higher risk to die comparing to patients with a 0/4 score. This score was validated by a 10-fold cross-validation (prediction accuracy of 82%). Finally, in Binet stage A patients (n=77), this score remained relevant and significant for TFS and OS prediction (HR=18.56, P<0.0001 and HR=12.5, P=0.0068, respectively). Conclusions: we showed that (i) miR-29c and miR-223 levels were decreased in poor prognosis patients regarding several well-known prognostic factors; (ii) a low level of these two microRNAs is thus associated to disease aggressiveness, tumor burden and poor clinical evolution; (iii) we also showed that these two microRNAs could predict TFS and OS; (iv) we proposed a qPCR score to better individualize evolution of a particular CLL patient. This score will help to identify patients who will need early therapy and require thus a closer follow-up.

BIRC3 disruption and Copy Number Aberrations in Chronic Lymphocytic Leukemia (CLL) Patients with 11q Deletion

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3295-3295
Author(s):  
Ilaria Del Giudice ◽  
Silvia Bonina ◽  
Marilisa Marinelli ◽  
Luciana Cafforio ◽  
Sara Raponi ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Copy Number ◽  
Poor Prognosis ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Chromosome Analysis ◽  
Lymphocytic Leukemia ◽  
The Other ◽  
11Q Deletion

Abstract Introduction. Chronic lymphocytic leukemia (CLL) with 11q deletion has been associated to a poor prognosis, but the clinical course of patients carrying this lesion is variable. This aberration, most often monoallelic, is present in 10-17% of newly diagnosed CLL and in 20-30% of patients with progressive or chemorefractory disease. The minimal deleted region (MDR) (2-3 Mbp) is located on the 11q22.3-q23.1 region and includes ATM. Moreover, 30-40% of 11q- CLL have also an inactivating ATM mutation on the other allele. The deleted region on 11q can also include BIRC3, a gene that is often deleted or mutated in advanced/chemorefractory stages of the disease. Although BIRC3 disruption has been associated to a poor prognosis, its prognostic implications in addition to ATM deletion are not well defined. The aim of this study was to perform a copy number aberration (CNA) and gene sequencing analyses on a cohort of CLL patients with 11q- in order to identify subgroups with potential prognostic relevance based on: i) the inclusion of BIRC3 in the deleted region; ii) the presence of BIRC3 mutation; iii) the presence of other CNAs. Methods. The study has included 55 untreated CLL patients followed at our Institution or enrolled in GIMEMA clinical trials (2003-2013). Genomic DNA was extracted from peripheral blood samples. CNA analysis was performed by genomic hybridization on the CytoScan HD array (Affymetrix), which contains more than 2.6 x 106 markers for copy number analysis and 750.000 SNPs. Data were analyzed using both Partek Genomics Suite and ChAS (Chromosome Analysis Suite, Affymetrix) software. The resulting CNAs were verified by visual examination of the plotted copy number profiles. BIRC3 mutations (exons 6-9) were evaluated by Sanger sequencing. Time to first treatment (TFT) was calculated from the date of diagnosis to the date of first therapy or last follow-up; progression-free survival (PFS) from the date of first therapy to the date of progression, death or last follow-up. Results. Baseline characteristics of the 55 cases were as follows: median age at diagnosis 59 years (range 39-84), male gender in 81.8% of patients, progressive disease in 62%. All patients showed 11q- by FISH (median 80%, range 25-99% of nuclei); germline IGHV were present in 96.4% of cases; TP53 deletion in 1 case and TP53 mutation in none; NOTCH1 mutation in 4/40 cases; SF3B1 mutation in 5/40 (all mutually exclusive with only 1 case having both SF3B1 and BIRC3 mutations). By CytoScan HD array, the size of 11q- was very variable, ranging from 0.36 Mbp to 65.14 Mbp; the MDR was located on 11q22.3 region, encompassing 4 genes (ACAT1, ATM, CUL5, NPAT). BIRC3 was included in the deleted region in 45/55 cases (81.8%) and was mutated in 4/54 (7.5%), being always deleted on the other allele. Beside 11q-, 51 cases (92.7%) showed several additional CNAs (average 4.9, range 1-14 per patient), with 5 recurrent lesions: 2p gain in 11 cases, del4(p15.2) in 6, del19(p13.3) in 6, 8q gain in 5 and del4(q22.1) in 4. BIRC3 deletion was not associated to the number of additional CNAs nor to specific CNA. After a follow-up of 59.6 months (range 7.4-229.7), 40 of 47 evaluable patients have received treatment (median TFT 15.8 months, range 0-167). BIRC3 deleted cases (n=37) showed a TFT not significantly different from WT cases (n=10). Conversely, BIRC3 mutation was associated to a shorter TFT (p <0.0001), 0.5 vs 19.3 months of WT cases. Notably, 3/4 cases with the biallelic BIRC3 disruption had a marked hyperleukocytosis at diagnosis (212.4-302.8 x 109L). The presence of additional CNAs was associated to a shorter, though not significant, TFT considering either >3 CNAs larger than 5 Mb (n=14) or >10 CNAs (n=5), or the presence of 2p gain, del4(p15.2), del19(p13.3) or 8q gain. So far, 22 patients have been evaluated for PFS after first-line therapy (median 28.7 months). BIRC3 deleted cases (n=17) were not associated to a shorter PFS compared to WT cases (n=5), in line with the results from Rose-Zerilli et al (Haematologica 2014). Conclusions. Among CLL with 11q-: 1) BIRC3 deletion involves more than 80% of cases, whilst the mutation is rare (7.5%); 2) BIRC3 deletion is not associated to a higher genomic complexity; 3) BIRC3 deletion does not seem to influence TFT or PFS of 11q- CLL; 4) BIRC3 mutation is strongly associated to a short TFT; 5) BIRC3 biallelic lesions can be associated to a marked hyperleucocytosis at diagnosis and immediate need of treatment. Disclosures No relevant conflicts of interest to declare.

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