Mutational Status and Gene Repertoire of IGHV-IGHD-IGHJ Rearrangements in Serbian Patients With Chronic Lymphocytic Leukemia
Само за регистроване кориснике
2012
Аутори
Karan-Đurašević, TeodoraPalibrk, Vuk
Kostić, Tatjana
Spasovski, Vesna
Nikčević, Gordana
Srzentić Dražilov, Sanja
Colović, Milica
Čolović, Nataša
Vidović, Ana
Antić, Darko
Mihaljević, Biljana
Pavlović, Sonja
Tošić, Nataša
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The mutational status and configuration of immunoglobulin heavy variable (IGHV) gene rearrangements was analyzed in 85 Serbian patients with chronic lymphocytic leukemia (CLL). We found that 55.3% of cases belonged to mutated and 44.7% to unmutated CLL, progressive disease predominating in the unmutated subset. IGHV gene use resembled that obtained for Mediterranean countries, except for underrepresentation of the IGHV4 subgroup in our cohort. Background: Chronic lymphocytic leukemia (CLL) results from the clonal expansion of mature B lymphocytes and is characterized by extreme clinical heterogeneity. One of the most reliable prognostic markers in chronic lymphocytic leukemia (CLL) is the mutational status of immunoglobulin heavy variable (IGHV) genes, which defines 2 subsets, mutated CLL (M-CLL) and unmutated CLL (U-CLL), with different clinical courses. Biased IGHV gene use between M-CLL and U-CLL clones, as well as population differences in the IGHV gene repertoire have been reporte...d. Patients and Methods: In this study, mutational status and configuration of IGHV-IGHD-IGHJ rearrangements in 85 Serbian patients were analyzed using reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing methodology. Results: We found that 55.3% of cases belonged to M-CLL and 44.7% belonged to U-CLL, with progressive disease predominating in the unmutated subset. Most frequently expressed was the IGHV3 subgroup (55.7%), followed by IGHV1 (27.3%), IGHV4 (12.5%), IGHV5 (2.3%), IGHV2 (1.1%), and IGHV6 (1.1%). The distribution of IGHD subgroups was as follows: IGHD3, 39.1%; IGHD2, 21.8%; IGHD6, 12.6%; IGHD1, 10.3%; IGHD4, 8%; IGHD5, 6.9%; and IGHD7, 1.1%. The most frequent IGHJ gene was IGHJ4 (48.9%), followed by IGHJ6 (28.4%), IGHJ3 (11.4%), and IGHJ5 (11.4%). In 15.3% of cases, heavy complementarity-determining region 3 (VH CDR3) amino acid sequences could be assigned to previously defined stereotyped clusters. Conclusions: Our study showed a strong correlation between IGHV gene mutational status and clinical course of CLL. IGHV gene use was comparable to that obtained for Mediterranean countries, with the exception of the IGHV4 subgroup, which was underrepresented in our cohort. Clinical Lymphoma, Myeloma & Leukemia, Vol. 12, No. 4, 252-60
Кључне речи:
VH CDR3 / Somatic hypermutation / Immunoglobulin heavy variable genes / Gene use / B-cell receptorИзвор:
Clinical Lymphoma Myeloma & Leukemia, 2012, 12, 4, 252-260Издавач:
- CIG Media Group, Lp, Dallas
Финансирање / пројекти:
- Ретке болести: молекуларна патофизиологија, дијагностички и терапијски модалитети и социјални, етички и правни аспекти (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41004)
DOI: 10.1016/j.clml.2012.03.005
ISSN: 2152-2650
PubMed: 22560084
WoS: 000307154200005
Scopus: 2-s2.0-84864274976
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Karan-Đurašević, Teodora AU - Palibrk, Vuk AU - Kostić, Tatjana AU - Spasovski, Vesna AU - Nikčević, Gordana AU - Srzentić Dražilov, Sanja AU - Colović, Milica AU - Čolović, Nataša AU - Vidović, Ana AU - Antić, Darko AU - Mihaljević, Biljana AU - Pavlović, Sonja AU - Tošić, Nataša PY - 2012 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/565 AB - The mutational status and configuration of immunoglobulin heavy variable (IGHV) gene rearrangements was analyzed in 85 Serbian patients with chronic lymphocytic leukemia (CLL). We found that 55.3% of cases belonged to mutated and 44.7% to unmutated CLL, progressive disease predominating in the unmutated subset. IGHV gene use resembled that obtained for Mediterranean countries, except for underrepresentation of the IGHV4 subgroup in our cohort. Background: Chronic lymphocytic leukemia (CLL) results from the clonal expansion of mature B lymphocytes and is characterized by extreme clinical heterogeneity. One of the most reliable prognostic markers in chronic lymphocytic leukemia (CLL) is the mutational status of immunoglobulin heavy variable (IGHV) genes, which defines 2 subsets, mutated CLL (M-CLL) and unmutated CLL (U-CLL), with different clinical courses. Biased IGHV gene use between M-CLL and U-CLL clones, as well as population differences in the IGHV gene repertoire have been reported. Patients and Methods: In this study, mutational status and configuration of IGHV-IGHD-IGHJ rearrangements in 85 Serbian patients were analyzed using reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing methodology. Results: We found that 55.3% of cases belonged to M-CLL and 44.7% belonged to U-CLL, with progressive disease predominating in the unmutated subset. Most frequently expressed was the IGHV3 subgroup (55.7%), followed by IGHV1 (27.3%), IGHV4 (12.5%), IGHV5 (2.3%), IGHV2 (1.1%), and IGHV6 (1.1%). The distribution of IGHD subgroups was as follows: IGHD3, 39.1%; IGHD2, 21.8%; IGHD6, 12.6%; IGHD1, 10.3%; IGHD4, 8%; IGHD5, 6.9%; and IGHD7, 1.1%. The most frequent IGHJ gene was IGHJ4 (48.9%), followed by IGHJ6 (28.4%), IGHJ3 (11.4%), and IGHJ5 (11.4%). In 15.3% of cases, heavy complementarity-determining region 3 (VH CDR3) amino acid sequences could be assigned to previously defined stereotyped clusters. Conclusions: Our study showed a strong correlation between IGHV gene mutational status and clinical course of CLL. IGHV gene use was comparable to that obtained for Mediterranean countries, with the exception of the IGHV4 subgroup, which was underrepresented in our cohort. Clinical Lymphoma, Myeloma & Leukemia, Vol. 12, No. 4, 252-60 PB - CIG Media Group, Lp, Dallas T2 - Clinical Lymphoma Myeloma & Leukemia T1 - Mutational Status and Gene Repertoire of IGHV-IGHD-IGHJ Rearrangements in Serbian Patients With Chronic Lymphocytic Leukemia EP - 260 IS - 4 SP - 252 VL - 12 DO - 10.1016/j.clml.2012.03.005 ER -
@article{ author = "Karan-Đurašević, Teodora and Palibrk, Vuk and Kostić, Tatjana and Spasovski, Vesna and Nikčević, Gordana and Srzentić Dražilov, Sanja and Colović, Milica and Čolović, Nataša and Vidović, Ana and Antić, Darko and Mihaljević, Biljana and Pavlović, Sonja and Tošić, Nataša", year = "2012", abstract = "The mutational status and configuration of immunoglobulin heavy variable (IGHV) gene rearrangements was analyzed in 85 Serbian patients with chronic lymphocytic leukemia (CLL). We found that 55.3% of cases belonged to mutated and 44.7% to unmutated CLL, progressive disease predominating in the unmutated subset. IGHV gene use resembled that obtained for Mediterranean countries, except for underrepresentation of the IGHV4 subgroup in our cohort. Background: Chronic lymphocytic leukemia (CLL) results from the clonal expansion of mature B lymphocytes and is characterized by extreme clinical heterogeneity. One of the most reliable prognostic markers in chronic lymphocytic leukemia (CLL) is the mutational status of immunoglobulin heavy variable (IGHV) genes, which defines 2 subsets, mutated CLL (M-CLL) and unmutated CLL (U-CLL), with different clinical courses. Biased IGHV gene use between M-CLL and U-CLL clones, as well as population differences in the IGHV gene repertoire have been reported. Patients and Methods: In this study, mutational status and configuration of IGHV-IGHD-IGHJ rearrangements in 85 Serbian patients were analyzed using reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing methodology. Results: We found that 55.3% of cases belonged to M-CLL and 44.7% belonged to U-CLL, with progressive disease predominating in the unmutated subset. Most frequently expressed was the IGHV3 subgroup (55.7%), followed by IGHV1 (27.3%), IGHV4 (12.5%), IGHV5 (2.3%), IGHV2 (1.1%), and IGHV6 (1.1%). The distribution of IGHD subgroups was as follows: IGHD3, 39.1%; IGHD2, 21.8%; IGHD6, 12.6%; IGHD1, 10.3%; IGHD4, 8%; IGHD5, 6.9%; and IGHD7, 1.1%. The most frequent IGHJ gene was IGHJ4 (48.9%), followed by IGHJ6 (28.4%), IGHJ3 (11.4%), and IGHJ5 (11.4%). In 15.3% of cases, heavy complementarity-determining region 3 (VH CDR3) amino acid sequences could be assigned to previously defined stereotyped clusters. Conclusions: Our study showed a strong correlation between IGHV gene mutational status and clinical course of CLL. IGHV gene use was comparable to that obtained for Mediterranean countries, with the exception of the IGHV4 subgroup, which was underrepresented in our cohort. Clinical Lymphoma, Myeloma & Leukemia, Vol. 12, No. 4, 252-60", publisher = "CIG Media Group, Lp, Dallas", journal = "Clinical Lymphoma Myeloma & Leukemia", title = "Mutational Status and Gene Repertoire of IGHV-IGHD-IGHJ Rearrangements in Serbian Patients With Chronic Lymphocytic Leukemia", pages = "260-252", number = "4", volume = "12", doi = "10.1016/j.clml.2012.03.005" }
Karan-Đurašević, T., Palibrk, V., Kostić, T., Spasovski, V., Nikčević, G., Srzentić Dražilov, S., Colović, M., Čolović, N., Vidović, A., Antić, D., Mihaljević, B., Pavlović, S.,& Tošić, N.. (2012). Mutational Status and Gene Repertoire of IGHV-IGHD-IGHJ Rearrangements in Serbian Patients With Chronic Lymphocytic Leukemia. in Clinical Lymphoma Myeloma & Leukemia CIG Media Group, Lp, Dallas., 12(4), 252-260. https://doi.org/10.1016/j.clml.2012.03.005
Karan-Đurašević T, Palibrk V, Kostić T, Spasovski V, Nikčević G, Srzentić Dražilov S, Colović M, Čolović N, Vidović A, Antić D, Mihaljević B, Pavlović S, Tošić N. Mutational Status and Gene Repertoire of IGHV-IGHD-IGHJ Rearrangements in Serbian Patients With Chronic Lymphocytic Leukemia. in Clinical Lymphoma Myeloma & Leukemia. 2012;12(4):252-260. doi:10.1016/j.clml.2012.03.005 .
Karan-Đurašević, Teodora, Palibrk, Vuk, Kostić, Tatjana, Spasovski, Vesna, Nikčević, Gordana, Srzentić Dražilov, Sanja, Colović, Milica, Čolović, Nataša, Vidović, Ana, Antić, Darko, Mihaljević, Biljana, Pavlović, Sonja, Tošić, Nataša, "Mutational Status and Gene Repertoire of IGHV-IGHD-IGHJ Rearrangements in Serbian Patients With Chronic Lymphocytic Leukemia" in Clinical Lymphoma Myeloma & Leukemia, 12, no. 4 (2012):252-260, https://doi.org/10.1016/j.clml.2012.03.005 . .