Deletion analysis of chromosome 13q14.3 and characterisation of an alternative splice form of LEU1 in B cell chronic lymphocytic leukemia

Rowntree, Clare; Duke, Veronique; Panayiotidis, Panayiotis; Kotsi, P.; Palmisano, GL; Hoffbrand, A. V.; Foroni, Letizia

doi:10.1038/sj.leu.2402551

Cited by 23 publications

(19 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hemizygous and/or homozygous deletions of chromosome band 13q14 constitute the most frequent cytogenetic abnormalities in CLL and are seen in approximately half of the cases [2, 3]. Trisomy 12 (15%), 11q22–23 deletion (12%), and 17p13 deletion (8%) were less frequent [3, 4]. …”

Section: Introductionmentioning

confidence: 99%

Bcl‐2 level as a biomarker for 13q14 deletion in CLL

Degheidy¹,

Gadalla

Farooqui

et al. 2013

Cytometry Part B Clinical

View full text Add to dashboard Cite

Background Deletion 13q14.3 is the most common cytogenetic abnormality in chronic lymphocytic leukemia (CLL). Previously it was reported that miR-15/16 is the target of 13q14 deletions and plays a tumor suppressor role by suppressing Bcl-2. Therefore, Bcl-2 expression was examined more closely to determine whether it would predict 13q14 deletion status. Methods A multi-color flow panel consisting of anti-Bcl-2/anti-lambda/anti-kappa/CD19/CD5/CD3/CD20 was performed. The ability of Bcl-2 to predict 13q14 deletion was tested using the conventional Bcl-2 index (c-index): mean fluorescence intensity (MFI) of CLL clone/MFI of residual T-cells. Fifty-four untreated CLL/MBL patients were studied. Bimodal Bcl-2 expression was evaluated to test the ability of Bcl-2 to detect intra-clonal heterogeneity. Other CLL prognostic markers including CD38, CD49d, CD26, and CD69 were evaluated. FISH was performed on selected sorted populations. Results The Bcl-2 c-index strongly predicts del13q14 p<0.0001. A statistically significant association was observed between the percentage of cells carrying the deletion and the level of Bcl-2 expression p<0.05. Cells sorted based on Bcl-2 expression showed enrichment of both hemi-and homozygous del 13q14 cells. Also we observed that an alteration in Bcl-2 level over time predicts changes in 13q14 deletion status. And a statistically significant correlation between the bimodal pattern of CD69 expression and the presence of 13q14 deletion was found p<0.0001. Conclusion Bcl-2 expression using the c-index strongly predicts 13q14 deletion and can be used to distinguish homozygous, heterozygous, and diploid CLL clonal cells. Further systematic studies of this biomarker are needed for confirmation and expansion of these findings.

show abstract

Section: Introductionmentioning

confidence: 99%

Bcl‐2 level as a biomarker for 13q14 deletion in CLL

Degheidy¹,

Gadalla

Farooqui

et al. 2013

Cytometry Part B Clinical

View full text Add to dashboard Cite

show abstract

“…Attempts to delineate the minimal common deleted region (CDR) in CLL and MM cells lead to highlighting a region adjacent to marker D13S319 [9, 13, 15, 16]. This region encompasses an area containing the previously described tumor suppressor gene candidates DLEU1 , DLEU2 , RFP2 , and KCNRG as well as microRNAs miR-15a and miR-16-1 [9, 16–19].…”

Section: Introductionmentioning

confidence: 99%

“…This region encompasses an area containing the previously described tumor suppressor gene candidates DLEU1 , DLEU2 , RFP2 , and KCNRG as well as microRNAs miR-15a and miR-16-1 [9, 16–19]. DLEU1 and DLEU2 candidates are represented by a number of non-coding RNAs [15, 20]. Direct sequencing and single-strand conformation polymorphism (SSCP) screening of the RFP2 gene encoding E3 ubiquitin ligase revealed no mutations [13, 19, 21].…”

Section: Introductionmentioning

confidence: 99%

Pro-apoptotic and antiproliferative activity of human KCNRG, a putative tumor suppressor in 13q14 region

et al. 2009

View full text Add to dashboard Cite

Deletion of 13q14.3 and a candidate gene KCNRG (potassium channel regulating gene) is the most frequent chromosomal abnormality in B-cell chronic lymphocytic leukemia and is a common finding in multiple myeloma (MM). KCNRG protein may interfere with the normal assembly of the K+ channel proteins causing the suppression of Kv currents. We aimed to examine possible role of KCNRG haploinsufficiency in chronic lymphocytic leukemia (CLL) and MM cells. We performed detailed genomic analysis of the KCNRG locus; studied effects of the stable overexpression of KCNRG isoforms in RPMI-8226, HL-60, and LnCaP cells; and evaluated relative expression of its transcripts in various human lymphomas. Three MM cell lines and 35 CLL PBL samples were screened for KCNRG mutations. KCNRG exerts growth suppressive and pro-apoptotic effects in HL-60, LnCaP, and RPMI-8226 cells. Direct sequencing of KCNRG exons revealed point mutation delT in RPMI-8226 cell line. Levels of major isoform of KCNRG mRNA are lower in DLBL lymphomas compared to normal PBL samples, while levels of its minor mRNA are decreased across the broad range of the lymphoma types. The haploinsufficiency of KCNRG might be relevant to the progression of CLL and MM at least in a subset of patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s13277-009-0005-0) contains supplementary material, which is available to authorized users.

show abstract

“…Efforts by multiple groups have identified candidate genes within an f1 Mb stretch on chromosome 13 that have each been implicated in CLL del13q14 biology; nonetheless, mutations in these genes have not been identified and questions remain as to the validity of reducing the biology of del13q14 to a minimal deleted region or a single-gene mutation/expression event (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Analysis of del13q14 is further complicated by an evolving understanding of resident gene structure and the discovery of complex noncoding RNAs (20).…”

Section: Introductionmentioning

confidence: 99%

Integrated Genomic Profiling of Chronic Lymphocytic Leukemia Identifies Subtypes of Deletion 13q14

et al. 2008

View full text Add to dashboard Cite

Chronic lymphocytic leukemia (CLL) is a biologically heterogeneous illness with a variable clinical course. Loss of chromosomal material on chromosome 13 at cytoband 13q14 is the most frequent genetic abnormality in CLL, but the molecular aberrations underlying del13q14 in CLL remain incompletely characterized. We analyzed 171 CLL cases for loss of heterozygosity and subchromosomal copy loss on chromosome 13 in DNA from fluorescence-activated cell sorting-sorted CD19 + cells and paired buccal cells using the Affymetrix XbaI 50k SNP array platform. The resulting highresolution genomic maps, together with array-based measurements of expression levels of RNA in CLL cases with and without del13q14 and quantitative PCR-based expression analysis of selected genes, support the following conclusions: (a) del13q14 is heterogeneous and composed of multiple subtypes, with deletion of Rb or the miR15a/miR16 loci serving as anatomic landmarks, respectively; (b) del13q14 type Ia deletions are relatively uniform in length and extend from breakpoints close to the miR15a/miR16 cluster to a newly identified telomeric breakpoint cluster at the f50.2 to 50.5 Mb physical position; (c) LATS2 RNA levels are f2.6-fold to 2.8-fold lower in cases with del13q14 type I that do not delete Rb, as opposed to del13q14 type II or all other CLL cases; (d) PHLPP RNA is absent in f50% of CLL cases with del13q14; and (e) f15% of CLL cases display marked reductions in miR15a/miR16 expression that are often but not invariably associated with bi-allelic miR15a/miR16 loss. These data should aid future investigations into biological differences imparted on CLL by different del13q14 subtypes.

show abstract

Deletion analysis of chromosome 13q14.3 and characterisation of an alternative splice form of LEU1 in B cell chronic lymphocytic leukemia

Cited by 23 publications

References 37 publications

Bcl‐2 level as a biomarker for 13q14 deletion in CLL

Bcl‐2 level as a biomarker for 13q14 deletion in CLL

Pro-apoptotic and antiproliferative activity of human KCNRG, a putative tumor suppressor in 13q14 region

Integrated Genomic Profiling of Chronic Lymphocytic Leukemia Identifies Subtypes of Deletion 13q14

Contact Info

Product

Resources

About