Publications (6)20.47 Total impact
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Article: Concomitant JAK2 V617F-positive polycythemia vera and B-cell chronic lymphocytic leukemia in three patients originating from two separate hematopoietic stem cells.
American Journal of Hematology 11/2012; · 4.67 Impact Factor -
Article: Array-based karyotyping in chronic lymphocytic leukemia (CLL) detects new unbalanced abnormalities that escape conventional cytogenetics and CLL FISH panel.
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ABSTRACT: AIMS: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia with a very heterogeneous course. Progress in molecular genetic characterization of CLL has confirmed the prognostic role of unbalanced chromosomal abnormalities currently defined by molecular cytogenetic methods: conventional karyotyping and FISH. However, a significant percentage of genomic abnormalities escapes routine investigation due to the limitations of these methods. It is presently clear that some of these aberrations have impact on prognosis and disease progression. METHODS: We examined copy number changes in the tumor genomes of 50 CLL patients using bacterial artificial chromosome (BAC) and/or oligonucleotide array platforms. We compared the results of arrayCGH with those obtained by FISH and conventional cytogenetics and evaluated their clinical importance. RESULTS: A total of 111 copy number changes were detected in 43 patients (86%) with clonal abnormalities present in at least 23% of the cells. Moreover, 14 patients (28%) were found to have 39 genomic changes that had not been detected by standard cytogenetic and/or FISH analyses. These included possibly prognostically important recurrent 2p and 8q24 gains. The most frequent unbalanced changes involved chromosomes 18, 7, 3, 9 and 17. We also determined the minimal deleted region on chromosome 6q in 7 cases by chromosome 6/7 specific array. CONCLUSIONS: The results showed that a subset of potentially significant genomic aberrations in CLL is being missed by the current routine techniques. Further, we clearly demonstrated the robustness, high sensitivity and specificity of the arrayCGH analysis as well as its potential for use in routine screening of CLL.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia 06/2012; -
Article: Recurrent breakpoints in the 14q32.13/TCL1A region in mature B-cell neoplasms with villous lymphocytes.
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ABSTRACT: Abstract Genetic background of mature B cell neoplasms with villous lymphocytes is poorly understood. We identified a novel breakpoint region at 14q32.13 that was rearranged together with IGH/14q32.33 in 4 BRAF/V600E-negative leukemia/lymphoma cases with villous lymphocytes carrying either t(14;14)(q32.13;q32.33) (3 patients) or del(14)(q32.13q32.33) (1 patient). The 14q32.13 breakpoints were mapped by FISH in the region harboring the TCL1A/TCL1B/TCL6 genes, known to be affected by TCRA/D-mediated t(14;14)(q11;q32)/inv(14)(q11q32) occurring in T-cell leukemia/lymphoma. To identify the target of t(14;14)(q32.13;q32.33) and del(14)(q32.13q32.33), qRT-PCR analysis of 25 candidate genes located centromerically and telomerically to the 14q3213 breakpoint was performed. Any of the analyzed genes was commonly overexpressed in the presented cases. Of note, upregulated transcription of TCL1A was observed in 2 cases. In summary, we provide evidence that IGH-mediated chromosomal aberrations affecting the 14q32.13/TCL1A-TCL6 region are recurrent in mature B-cell neoplasms with villous lymphocytes. Despite extensive qRT-PCR studies, molecular consequences of these novel aberrations remain elusive.Leukemia & lymphoma 05/2012; · 2.40 Impact Factor -
Article: t(X;14)(p11.4;q32.33) is recurrent in marginal zone lymphoma and up-regulates GPR34.
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ABSTRACT: Genetic events underlying pathogenesis of nodal and extranodal marginal zone lymphoma are not completely understood. We report here a novel t(X;14)(p11.4;q32.33) identified in 4 lymphoma cases: 2 with a mucosa-associated lymphoid tissue lymphoma, one with a nodal marginal zone lymphoma and one with gastric diffuse large B-cell lymphoma. In all cases, lymphoma evolved from a previous auto-immune disorder. Fluorescence in situ hybridization and molecular studies showed that t(X;14), which is mediated by immunoglobulin heavy chain locus, targets the GPR34 gene at Xp11.4. Upregulation of GPR34 mRNA and aberrant expression of GPR34 protein has been demonstrated in 3 presented cases by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. GPR34 belongs to the largest family of cell surface molecules involved in signal transmission that play important roles in many physiological and pathological processes, including tumorigenesis. Although functional consequences of t(X;14) have not been identified, our studies suggest that up-regulated GPR34 activate neither nuclear factor-κB nor ELK-related tyrosine kinase.Haematologica 11/2011; 97(2):184-8. · 6.42 Impact Factor -
Article: Gain of chromosome 2p in chronic lymphocytic leukemia: significant heterogeneity and a new recurrent dicentric rearrangement.
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ABSTRACT: Array-based comparative genomic hybridization (arrayCGH) studies in chronic lymphocytic leukemia (CLL) have revealed novel recurrent chromosomal imbalances, such as a gain of chromosome 2p. However, a detailed cytogenetic analysis of the 2p gain region has not been elucidated. Here, we present cytogenetic and molecular cytogenetic analysis of 16 such cases selected from a group of 200 patients with CLL based on CGH and/or arrayCGH data. We revealed significant heterogeneity of the region of gain on 2p in CLL, including a new recurrent aberration: the dicentric chromosome, dic(2;18). In our cases, the region of gain involved three genes (MYCN, REL, and ALK) and was associated with an unmutated IgVH status in 14 out of 16 cases. We consider this aberration clinically important in CLL and suggest that an examination of the gene(s) located in region of gain should be included in the routine fluorescence in situ hybridization screening method used for patients with CLL.Leukemia & lymphoma 02/2010; 51(2):304-13. · 2.40 Impact Factor -
Article: Methylation analysis of the imprinted DLK1-GTL2 domain supports the random parental origin of the IGH-involving del(14q) in B-cell malignancies.
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ABSTRACT: Leukemias/lymphomas with IGH-involving del(14q)(1) commonly lose the DLK1-GTL2 imprinted domain that comprises several paternally and maternally expressed genes, including a cluster of microRNAs. Given that deletion of this region could lead to inactivation of a monoallelically expressed tumor suppressor gene, our study aimed at determination of the parental origin of del(14q/IGH). The designed allele-specific methylation study of the DLK1/GTL2 intergenic differentially methylated region allowed us to determine the parental origin of del(14q/IGH) in 9/20 analyzed cases. In six cases del(14q/IGH) was of the paternal origin and in three cases of the maternal origin. These findings argue against the concept that a TSG/anti-oncomir located in the imprinted region is systematically inactivated by a targeted deletion of its functional allele.Epigenetics: official journal of the DNA Methylation Society 10/2009; 4(7):469-75. · 4.58 Impact Factor
Top co-authors
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Institutions
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2012
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Palacký University of Olomouc
- Department of Hemato-Oncology
Olomouc, Olomoucky kraj, Czech Republic
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2009–2011
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KU Leuven
- Department of Human Genetics
Leuven, VLG, Belgium
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