11 results on '"Kminkova, J."'
Search Results
2. Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors
- Author
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Sutton, L.-A. Young, E. Baliakas, P. Hadzidimitriou, A. Moysiadis, T. Plevova, K. Rossi, D. Kminkova, J. Stalika, E. Pedersen, L.B. Malcikova, J. Agathangelidis, A. Davis, Z. Mansouri, L. Scarfò, L. Boudjoghra, M. Navarro, A. Muggen, A.F. Yan, X.-J. Nguyen-Khac, F. Larrayoz, M. Panagiotidis, P. Chiorazzi, N. Niemann, C.U. Belessi, C. Campo, E. Strefford, J.C. Langerak, A.W. Oscier, D. Gaidano, G. Pospisilova, S. Davi, F. Ghia, P. Stamatopoulos, K. Rosenquist, R. the European Research Initiative on CLL
- Abstract
We report on markedly different frequencies of genetic lesions within subsets of chronic lymphocytic leukemia patients carrying mutated or unmutated stereotyped B-cell receptor immunoglobulins in the largest cohort (n=565) studied for this purpose. By combining data on recurrent gene mutations (BIRC3, MYD88, NOTCH1, SF3B1 and TP53) and cytogenetic aberrations, we reveal a subset-biased acquisition of gene mutations. More specifically, the frequency of NOTCH1 mutations was found to be enriched in subsets expressing unmutated immunoglobulin genes, i.e. #1, #6, #8 and #59 (22-34%), often in association with trisomy 12, and was significantly different (P
- Published
- 2016
3. Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors
- Author
-
Sutton, L.-A. (L.), Young, E. (Emma), Baliakas, P. (P.), Hadzidimitriou, A. (A.), Moysiadis, T. (Theodoros), Plevova, K. (K.), Rossi, D. (Davide), Kminkova, J. (Jana), Stalika, E. (Evangelia), Pedersen, L.B. (Lone Bredo), Malčíková, J. (J.), Agathangelidis, A. (Andreas), Davis, Z. (Zadie), Mansouri, A. (Ahmed), Scarfó, L. (L.), Boudjoghra, M. (Myriam), Navarro, A. (Alba), Muggen, A.F. (Alice), Yan, X.-J. (Xiao-Jie), Nguyen-Khac, F. (Florence), Larrayoz, M. (Marta), Panagiotidis, P. (P.), Chiorazzi, N. (Nicholas), Niemann, C.U. (Carsten Utoft), Belessi, C. (C.), Campo, G. (Gianluca), Strefford, J.C. (J.), Langerak, A.W. (Anton), Oscier, D.G. (David Graham), Gaidano, G. (Gianluca), Pospisilova, D. (Dagmar), Davi, F. (Frédéric), Ghia, P. (Paolo), Stamatopoulos, K. (Kostas), Rosenquist, R. (R.), Sutton, L.-A. (L.), Young, E. (Emma), Baliakas, P. (P.), Hadzidimitriou, A. (A.), Moysiadis, T. (Theodoros), Plevova, K. (K.), Rossi, D. (Davide), Kminkova, J. (Jana), Stalika, E. (Evangelia), Pedersen, L.B. (Lone Bredo), Malčíková, J. (J.), Agathangelidis, A. (Andreas), Davis, Z. (Zadie), Mansouri, A. (Ahmed), Scarfó, L. (L.), Boudjoghra, M. (Myriam), Navarro, A. (Alba), Muggen, A.F. (Alice), Yan, X.-J. (Xiao-Jie), Nguyen-Khac, F. (Florence), Larrayoz, M. (Marta), Panagiotidis, P. (P.), Chiorazzi, N. (Nicholas), Niemann, C.U. (Carsten Utoft), Belessi, C. (C.), Campo, G. (Gianluca), Strefford, J.C. (J.), Langerak, A.W. (Anton), Oscier, D.G. (David Graham), Gaidano, G. (Gianluca), Pospisilova, D. (Dagmar), Davi, F. (Frédéric), Ghia, P. (Paolo), Stamatopoulos, K. (Kostas), and Rosenquist, R. (R.)
- Abstract
We report on markedly different frequencies of genetic lesions within subsets of chronic lymphocytic leukemia patients carrying mutated or unmutated stereotyped B-cell receptor immunoglobulins in the largest cohort (n=565) studied for this purpose. By combining data on recurrent gene mutations (BIRC3, MYD88, NOTCH1, SF3B1 and TP53) and cytogenetic aberrations, we reveal a subset-biased acquisition of gene mutations. More specifically, the frequency of NOTCH1 mutations was found to be enriched in subsets expressing unmutated immunoglobulin genes, i.e. #1, #6, #8 and #59 (22-34%), often in association with trisomy 12, and was significantly different (P<0.001) to the frequency observed in subset #2 (4%, aggressive disease, variable somatic hypermutation status) and subset #4 (1%, indolent disease, mutated immunoglobulin genes). Interestingly, subsets harboring a high frequency of NOTCH1 mutations were found to carry few (if any) SF3B1 mutations. This starkly contrasts with subsets #2 and #3 where, despite their immunogenetic differences, SF3B1 mutations occurred in 45% and 46% of cases, respectively. In addition, mutations within TP53, whilst enriched in subset #1 (16%), were rare in subsets #2 and #8 (both 2%), despite all being clinically aggressive. All subsets were negative for MYD88 mutations, whereas BIRC3 mutations were infrequent. Collectively, this striking bias and skewed distribution of mutations and cytogenetic aberrations within specific chronic lymphocytic leukemia subsets implies that the mechanisms underlying clinical aggressiveness are not uniform, but rather support the existence of distinct genetic pathways of clonal evolution governed by a particular stereotyped B-cell receptor selecting a certain molecular lesion(s).
- Published
- 2016
- Full Text
- View/download PDF
4. Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors
- Author
-
Sutton, LA, Young, E, Baliakas, P, Hadzidimitriou, A, Moysiadis, T, Plevova, K, Rossi, D, Kminkova, J, Stalika, E, Pedersen, LB, Malcikova, J, Agathangelidis, A, Davis, Z, Mansouri, L, Scarfo, L, Boudjoghra, M, Navarro, A, Muggen, Alice, Yan, XJ, Nguyen-Khac, F, Larrayoz, M, Panagiotidis, P, Chiorazzi, N, Niemann, CU, Belessi, C, Campo, E, Strefford, JC, Langerak, Ton, Oscier, D, Gaidano, G, Pospisilova, S, Davi, F, Ghia, P, Stamatopoulos, K, Rosenquist, R, Sutton, LA, Young, E, Baliakas, P, Hadzidimitriou, A, Moysiadis, T, Plevova, K, Rossi, D, Kminkova, J, Stalika, E, Pedersen, LB, Malcikova, J, Agathangelidis, A, Davis, Z, Mansouri, L, Scarfo, L, Boudjoghra, M, Navarro, A, Muggen, Alice, Yan, XJ, Nguyen-Khac, F, Larrayoz, M, Panagiotidis, P, Chiorazzi, N, Niemann, CU, Belessi, C, Campo, E, Strefford, JC, Langerak, Ton, Oscier, D, Gaidano, G, Pospisilova, S, Davi, F, Ghia, P, Stamatopoulos, K, and Rosenquist, R
- Abstract
We report on markedly different frequencies of genetic lesions within subsets of chronic lymphocytic leukemia patients carrying mutated or unmutated stereotyped B-cell receptor immunoglobulins in the largest cohort (n=565) studied for this purpose. By combining data on recurrent gene mutations (BIRC3, MYD88, NOTCH1, SF3B1 and TP53) and cytogenetic aberrations, we reveal a subset-biased acquisition of gene mutations. More specifically, the frequency of NOTCH1 mutations was found to be enriched in subsets expressing unmutated immunoglobulin genes, i.e. #1, #6, #8 and #59 (22-34%), often in association with trisomy 12, and was significantly different (P<0.001) to the frequency observed in subset #2 (4%, aggressive disease, variable somatic hypermutation status) and subset #4 (1%, indolent disease, mutated immunoglobulin genes). Interestingly, subsets harboring a high frequency of NOTCH1 mutations were found to carry few (if any) SF3B1 mutations. This starkly contrasts with subsets #2 and #3 where, despite their immunogenetic differences, SF3B1 mutations occurred in 45% and 46% of cases, respectively. In addition, mutations within TP53, whilst enriched in subset #1 (16%), were rare in subsets# 2 and #8 (both 2%), despite all being clinically aggressive. All subsets were negative for MYD88 mutations, whereas BIRC3 mutations were infrequent. Collectively, this striking bias and skewed distribution of mutations and cytogenetic aberrations within specific chronic lymphocytic leukemia subsets implies that the mechanisms underlying clinical aggressiveness are not uniform, but rather support the existence of distinct genetic pathways of clonal evolution governed by a particular stereotyped B-cell receptor selecting a certain molecular lesion(s).
- Published
- 2016
5. Recurrent mutations refine prognosis in chronic lymphocytic leukemia
- Author
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Baliakas, Panagiotis, Hadzidimitriou, A, Sutton, Lesley Ann, Rossi, D, Minga, E, Villamor, N, Larrayoz, M, Kminkova, J, Agathangelidis, A, Davis, Z, Tausch, E, Stalika, E, Kantorova, B, Mansouri, Larry, Scarfò, L, Cortese, Diego, Navrkalova, V, Rose-Zerilli, M J J, Smedby, K E, Juliusson, G, Anagnostopoulos, A, Makris, A M, Navarro, A, Delgado, J, Oscier, D, Belessi, C, Stilgenbauer, S, Ghia, P, Pospisilova, S, Gaidano, G, Campo, E, Strefford, J C, Stamatopoulos, Kostas, Rosenquist, Richard, Baliakas, Panagiotis, Hadzidimitriou, A, Sutton, Lesley Ann, Rossi, D, Minga, E, Villamor, N, Larrayoz, M, Kminkova, J, Agathangelidis, A, Davis, Z, Tausch, E, Stalika, E, Kantorova, B, Mansouri, Larry, Scarfò, L, Cortese, Diego, Navrkalova, V, Rose-Zerilli, M J J, Smedby, K E, Juliusson, G, Anagnostopoulos, A, Makris, A M, Navarro, A, Delgado, J, Oscier, D, Belessi, C, Stilgenbauer, S, Ghia, P, Pospisilova, S, Gaidano, G, Campo, E, Strefford, J C, Stamatopoulos, Kostas, and Rosenquist, Richard
- Abstract
Through the European Research Initiative on chronic lymphocytic leukemia (CLL) (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1 (n=3334), SF3B1 (n=2322), TP53 (n=2309), MYD88 (n=1080) and BIRC3 (n=919) genes, mainly at diagnosis (75%) and before treatment (>90%). BIRC3 mutations (2.5%) were associated with unmutated IGHV genes (U-CLL), del(11q) and trisomy 12, whereas MYD88 mutations (2.2%) were exclusively found among M-CLL. NOTCH1, SF3B1 and TP53 exhibited variable frequencies and were mostly enriched within clinically aggressive cases. Interestingly, as the timespan between diagnosis and mutational screening increased, so too did the incidence of SF3B1 mutations; no such increase was observed for NOTCH1 mutations. Regarding the clinical impact, NOTCH1 mutations, SF3B1 mutations and TP53 aberrations (deletion/mutation, TP53ab) correlated with shorter time-to-first-treatment (P<0.0001) in 889 treatment-naive Binet stage A cases. In multivariate analysis (n=774), SF3B1 mutations and TP53ab along with del(11q) and U-CLL, but not NOTCH1 mutations, retained independent significance. Importantly, TP53ab and SF3B1 mutations had an adverse impact even in U-CLL. In conclusion, we support the clinical relevance of novel recurrent mutations in CLL, highlighting the adverse impact of SF3B1 and TP53 mutations, even independent of IGHV mutational status, thus underscoring the need for urgent standardization/harmonization of the detection methods., De tre sista författarna delar sistaförfattarskapet.
- Published
- 2015
- Full Text
- View/download PDF
6. ATM mutations uniformly lead to ATM dysfunction in chronic lymphocytic leukemia: application of functional test using doxorubicin
- Author
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Navrkalova, V., primary, Sebejova, L., additional, Zemanova, J., additional, Kminkova, J., additional, Kubesova, B., additional, Malcikova, J., additional, Mraz, M., additional, Smardova, J., additional, Pavlova, S., additional, Doubek, M., additional, Brychtova, Y., additional, Potesil, D., additional, Nemethova, V., additional, Mayer, J., additional, Pospisilova, S., additional, and Trbusek, M., additional
- Published
- 2013
- Full Text
- View/download PDF
7. Recurrent mutations refine prognosis in chronic lymphocytic leukemia
- Author
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Kostas Stamatopoulos, Achilles Anagnostopoulos, Karin E. Smedby, Diego Cortese, Neus Villamor, Alba Navarro, C. Belessi, La. Sutton, E. Minga, Larry Mansouri, Gianluca Gaidano, Eugen Tausch, Paolo Ghia, Richard Rosenquist, Veronika Navrkalová, Šárka Pospíšilová, Jana Kminkova, Julio Delgado, Anastasia Hadzidimitriou, Lydia Scarfò, Gunnar Juliusson, Andreas Agathangelidis, Davide Rossi, Jonathan C. Strefford, Zadie Davis, Antonios M. Makris, Matthew J. J. Rose-Zerilli, David Oscier, Stephan Stilgenbauer, Panagiotis Baliakas, Elias Campo, Barbara Kantorová, Marta Larrayoz, Evangelia Stalika, Baliakas, P., Hadzidimitriou, A., Sutton, L. -A., Rossi, D., Minga, E., Villamor, N., Larrayoz, M., Kminkova, J., Agathangelidis, A., Davis, Z., Tausch, E., Stalika, E., Kantorova, B., Mansouri, L., Scarfo', L., Cortese, D., Navrkalova, V., Rose-Zerilli, M. J. J., Smedby, K. E., Juliusson, G., Anagnostopoulos, A., Makris, A. M., Navarro, A., Delgado, J., Oscier, D., Belessi, C., Stilgenbauer, S., Ghia, P., Pospisilova, S., Gaidano, G., Campo, E., Strefford, J. C., Stamatopoulos, K., and Rosenquist, R.
- Subjects
Oncology ,Male ,Cancer Research ,Time Factors ,Chronic lymphocytic leukemia ,DNA Mutational Analysis ,medicine.disease_cause ,0302 clinical medicine ,Recurrence ,hemic and lymphatic diseases ,Receptor, Notch1 ,0303 health sciences ,Mutation ,Hematology ,Middle Aged ,Prognosis ,3. Good health ,Europe ,Leukemia ,030220 oncology & carcinogenesis ,Female ,RNA Splicing Factors ,IGHV@ ,medicine.medical_specialty ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Cytogenetics ,Internal medicine ,medicine ,Humans ,Clinical significance ,neoplasms ,030304 developmental biology ,Aged ,business.industry ,Ribonucleoprotein, U2 Small Nuclear ,medicine.disease ,Phosphoproteins ,Leukemia, Lymphocytic, Chronic, B-Cell ,Lymphoma ,Immunology ,Multivariate Analysis ,Tumor Suppressor Protein p53 ,business ,Trisomy ,Gene Deletion - Abstract
Through the European Research Initiative on chronic lymphocytic leukemia (CLL) (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1 (n=3334), SF3B1 (n=2322), TP53 (n=2309), MYD88 (n=1080) and BIRC3 (n=919) genes, mainly at diagnosis (75%) and before treatment (>90%). BIRC3 mutations (2.5%) were associated with unmutated IGHV genes (U-CLL), del(11q) and trisomy 12, whereas MYD88 mutations (2.2%) were exclusively found among M-CLL. NOTCH1, SF3B1 and TP53 exhibited variable frequencies and were mostly enriched within clinically aggressive cases. Interestingly, as the timespan between diagnosis and mutational screening increased, so too did the incidence of SF3B1 mutations; no such increase was observed for NOTCH1 mutations. Regarding the clinical impact, NOTCH1 mutations, SF3B1 mutations and TP53 aberrations (deletion/mutation, TP53ab) correlated with shorter time-to-first-treatment (P
- Published
- 2014
- Full Text
- View/download PDF
8. Prognostic relevance of MYD88 mutations in CLL: the jury is still out
- Author
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Richard Rosenquist, Lesley-Ann Sutton, Davide Rossi, Paolo Ghia, Lydia Scarfò, Andreas Agathangelidis, Gianluca Gaidano, Šárka Pospíšilová, Jana Kminkova, Anastasia Hadzidimitriou, Kostas Stamatopoulos, Panagiotis Baliakas, Baliakas, P, Hadzidimitriou, A, Agathangelidis, A, Rossi, D, Sutton, La, Kminkova, J, Scarfo, L, Pospisilova, S, Gaidano, G, Stamatopoulos, K, Ghia, P, and Rosenquist, R
- Subjects
Adult ,Male ,Chronic lymphocytic leukemia ,Immunology ,Kaplan-Meier Estimate ,medicine.disease_cause ,Biochemistry ,Genome ,03 medical and health sciences ,Exon ,0302 clinical medicine ,hemic and lymphatic diseases ,Biomarkers, Tumor ,medicine ,Humans ,Gene ,Aged ,030304 developmental biology ,Aged, 80 and over ,Genetics ,0303 health sciences ,Mutation ,business.industry ,Cell Biology ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,3. Good health ,Leukemia ,030220 oncology & carcinogenesis ,Myeloid Differentiation Factor 88 ,Female ,business ,IGHV@ - Abstract
Genome surveys have offered a comprehensive view of the genetic landscape of chronic lymphocytic leukemia (CLL), identifying several recurrently mutated genes, including myeloid differentiation primary response 88 (MYD88). The predominant mutation concerns a p.L265P substitution within exon 5,1,2 which leads to constitutive nuclear factor kappaB stimulation, thus conferring a proliferation and survival advantage to the mutant cells.1 MYD88 mutations reach up to 2% to 5% in CLL and are strikingly enriched among patients expressing mutated IGHV genes (M-CLL).
- Published
- 2015
9. Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors.
- Author
-
Sutton LA, Young E, Baliakas P, Hadzidimitriou A, Moysiadis T, Plevova K, Rossi D, Kminkova J, Stalika E, Pedersen LB, Malcikova J, Agathangelidis A, Davis Z, Mansouri L, Scarfò L, Boudjoghra M, Navarro A, Muggen AF, Yan XJ, Nguyen-Khac F, Larrayoz M, Panagiotidis P, Chiorazzi N, Niemann CU, Belessi C, Campo E, Strefford JC, Langerak AW, Oscier D, Gaidano G, Pospisilova S, Davi F, Ghia P, Stamatopoulos K, and Rosenquist R
- Subjects
- Complementarity Determining Regions genetics, Cytogenetic Analysis, Female, Gene Frequency, Gene Rearrangement, B-Lymphocyte, Genes, Immunoglobulin, Humans, Immunoglobulin Heavy Chains genetics, Immunoglobulin Joining Region genetics, Immunoglobulin Variable Region genetics, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Male, Polymorphism, Single Nucleotide, Prognosis, Biomarkers, Tumor, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Mutation, Receptors, Antigen, B-Cell genetics, Receptors, Antigen, B-Cell metabolism
- Abstract
We report on markedly different frequencies of genetic lesions within subsets of chronic lymphocytic leukemia patients carrying mutated or unmutated stereotyped B-cell receptor immunoglobulins in the largest cohort (n=565) studied for this purpose. By combining data on recurrent gene mutations (BIRC3, MYD88, NOTCH1, SF3B1 and TP53) and cytogenetic aberrations, we reveal a subset-biased acquisition of gene mutations. More specifically, the frequency of NOTCH1 mutations was found to be enriched in subsets expressing unmutated immunoglobulin genes, i.e. #1, #6, #8 and #59 (22-34%), often in association with trisomy 12, and was significantly different (P<0.001) to the frequency observed in subset #2 (4%, aggressive disease, variable somatic hypermutation status) and subset #4 (1%, indolent disease, mutated immunoglobulin genes). Interestingly, subsets harboring a high frequency of NOTCH1 mutations were found to carry few (if any) SF3B1 mutations. This starkly contrasts with subsets #2 and #3 where, despite their immunogenetic differences, SF3B1 mutations occurred in 45% and 46% of cases, respectively. In addition, mutations within TP53, whilst enriched in subset #1 (16%), were rare in subsets #2 and #8 (both 2%), despite all being clinically aggressive. All subsets were negative for MYD88 mutations, whereas BIRC3 mutations were infrequent. Collectively, this striking bias and skewed distribution of mutations and cytogenetic aberrations within specific chronic lymphocytic leukemia subsets implies that the mechanisms underlying clinical aggressiveness are not uniform, but rather support the existence of distinct genetic pathways of clonal evolution governed by a particular stereotyped B-cell receptor selecting a certain molecular lesion(s)., (Copyright© Ferrata Storti Foundation.)
- Published
- 2016
- Full Text
- View/download PDF
10. Prognostic relevance of MYD88 mutations in CLL: the jury is still out.
- Author
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Baliakas P, Hadzidimitriou A, Agathangelidis A, Rossi D, Sutton LA, Kminkova J, Scarfo L, Pospisilova S, Gaidano G, Stamatopoulos K, Ghia P, and Rosenquist R
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Kaplan-Meier Estimate, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Male, Middle Aged, Mutation, Prognosis, Biomarkers, Tumor genetics, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Myeloid Differentiation Factor 88 genetics
- Published
- 2015
- Full Text
- View/download PDF
11. Identification of novel sequence variations in microRNAs in chronic lymphocytic leukemia.
- Author
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Kminkova J, Mraz M, Zaprazna K, Navrkalova V, Tichy B, Plevova K, Malcikova J, Cerna K, Rausch T, Benes V, Brychtova Y, Doubek M, Mayer J, and Pospisilova S
- Subjects
- Adult, Aged, Alleles, Chromosome Aberrations, Female, Gene Expression Regulation, Leukemic, Gene Frequency, Germ-Line Mutation, Humans, Immunoglobulin Heavy Chains genetics, Male, MicroRNAs chemistry, Middle Aged, Mutation, Nucleic Acid Conformation, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Genetic Variation, Leukemia, Lymphocytic, Chronic, B-Cell genetics, MicroRNAs genetics
- Abstract
MicroRNA (miRNA) expression is deregulated in many tumors including chronic lymphocytic leukemia (CLL). Although the particular mechanism(s) responsible for their aberrant expression is not well characterized, the presence of mutations and single-nucleotide polymorphisms (SNPs) in miRNA genes, possibly affecting their secondary structure and expression, has been described. In CLL; however, the impact and frequency of such variations have yet to be elucidated. Using a custom resequencing microarray, we screened sequence variations in 109 cancer-related pre-miRNAs in 98 CLL patients. Additionally, the primary regions of miR-29b-2/29c and miR-16-1 were analyzed by Sanger sequencing in another cohort of 213 and 193 CLL patients, respectively. Altogether, we describe six novel miR-sequence variations and the presence of SNPs (n = 27), most of which changed the miR-secondary structure. Moreover, some of the identified SNPs have a significantly different frequency in CLL when compared with a control population. Additionally, we identified a novel variation in miR-16-1 that had not been described previously in CLL patients. We show that this variation affects the expression of mature miR-16-1. We also show that the expression of another miRNA with pathogenetic relevance for CLL, namely miR-29b-2, is influenced by the presence of a polymorphic insertion, which is more frequent in CLL than in a control population. Altogether, these data suggest that sequence variations may occur during CLL development and/or progression.
- Published
- 2014
- Full Text
- View/download PDF
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