Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies
2012
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Аутори
Puda, AnaMilosević, Jelena D.
Berg, Tiina
Klampfl, Thorsten
Harutyunyan, Ashot S.
Gisslinger, Bettina
Rumi, Elisa
Pietra, Daniela
Malcovati, Luca
Elena, Chiara
Doubek, Michael
Steurer, Michael
Tošić, Nataša
Pavlović, Sonja
Guglielmelli, Paola
Pieri, Lisa
Vannucchi, Alessandro M.
Gisslinger, Heinz
Cazzola, Mario
Kralovics, Robert
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Chronic myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) have an inherent tendency to progress to acute myeloid leukemia (AML). Using high-resolution SNP microarrays, we studied a total of 517 MPN and MDS patients in different disease stages, including 77 AML cases with previous history of MPN (N = 46) or MDS (N = 31). Frequent chromosomal deletions of variable sizes were detected, allowing the mapping of putative tumor suppressor genes involved in the leukemic transformation process. We detected frequent deletions on the short arm of chromosome 6 (del6p). The common deleted region on 6p mapped to a 1.1-Mb region and contained only the JARID2 genemember of the polycomb repressive complex 2 (PRC2). When we compared the frequency of del6p between chronic and leukemic phase, we observed a strong association of del6p with leukemic transformation (P = 0.0033). Subsequently, analysis of deletion profiles of other PRC2 members revealed frequent losses of genes such as EZ...H2, AEBP2, and SUZ12; however, the deletions targeting these genes were large. We also identified two patients with homozygous losses of JARID2 and AEBP2. We observed frequent codeletion of AEBP2 and ETV6, and similarly, SUZ12 and NF1. Using next generation exome sequencing of 40 patients, we identified only one somatic mutation in the PRC2 complex member SUZ12. As the frequency of point mutations in PRC2 members was found to be low, deletions were the main type of lesions targeting PRC2 complex members. Our study suggests an essential role of the PRC2 complex in the leukemic transformation of chronic myeloid disorders. Am. J. Hematol. 2012.
Извор:
American Journal of Hematology, 2012, 87, 3, 245-250Издавач:
- Wiley, Hoboken
Финансирање / пројекти:
- Austrian Science Fund [P23257-B12]
- MPN Research Foundation
- Fondazione Cariplo
- Regione Lombardia
- MPO [FR-TI2/254]
- Associazione Italiana per la Ricerca sul Cancro (AIRC, Milano) [1005, IG 9034]
- Austrian Science Fund (FWF) [P 23257] Funding Source: researchfish
DOI: 10.1002/ajh.22257
ISSN: 0361-8609
PubMed: 22190018
WoS: 000300449100001
Scopus: 2-s2.0-84857051756
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Puda, Ana AU - Milosević, Jelena D. AU - Berg, Tiina AU - Klampfl, Thorsten AU - Harutyunyan, Ashot S. AU - Gisslinger, Bettina AU - Rumi, Elisa AU - Pietra, Daniela AU - Malcovati, Luca AU - Elena, Chiara AU - Doubek, Michael AU - Steurer, Michael AU - Tošić, Nataša AU - Pavlović, Sonja AU - Guglielmelli, Paola AU - Pieri, Lisa AU - Vannucchi, Alessandro M. AU - Gisslinger, Heinz AU - Cazzola, Mario AU - Kralovics, Robert PY - 2012 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/601 AB - Chronic myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) have an inherent tendency to progress to acute myeloid leukemia (AML). Using high-resolution SNP microarrays, we studied a total of 517 MPN and MDS patients in different disease stages, including 77 AML cases with previous history of MPN (N = 46) or MDS (N = 31). Frequent chromosomal deletions of variable sizes were detected, allowing the mapping of putative tumor suppressor genes involved in the leukemic transformation process. We detected frequent deletions on the short arm of chromosome 6 (del6p). The common deleted region on 6p mapped to a 1.1-Mb region and contained only the JARID2 genemember of the polycomb repressive complex 2 (PRC2). When we compared the frequency of del6p between chronic and leukemic phase, we observed a strong association of del6p with leukemic transformation (P = 0.0033). Subsequently, analysis of deletion profiles of other PRC2 members revealed frequent losses of genes such as EZH2, AEBP2, and SUZ12; however, the deletions targeting these genes were large. We also identified two patients with homozygous losses of JARID2 and AEBP2. We observed frequent codeletion of AEBP2 and ETV6, and similarly, SUZ12 and NF1. Using next generation exome sequencing of 40 patients, we identified only one somatic mutation in the PRC2 complex member SUZ12. As the frequency of point mutations in PRC2 members was found to be low, deletions were the main type of lesions targeting PRC2 complex members. Our study suggests an essential role of the PRC2 complex in the leukemic transformation of chronic myeloid disorders. Am. J. Hematol. 2012. PB - Wiley, Hoboken T2 - American Journal of Hematology T1 - Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies EP - 250 IS - 3 SP - 245 VL - 87 DO - 10.1002/ajh.22257 ER -
@article{ author = "Puda, Ana and Milosević, Jelena D. and Berg, Tiina and Klampfl, Thorsten and Harutyunyan, Ashot S. and Gisslinger, Bettina and Rumi, Elisa and Pietra, Daniela and Malcovati, Luca and Elena, Chiara and Doubek, Michael and Steurer, Michael and Tošić, Nataša and Pavlović, Sonja and Guglielmelli, Paola and Pieri, Lisa and Vannucchi, Alessandro M. and Gisslinger, Heinz and Cazzola, Mario and Kralovics, Robert", year = "2012", abstract = "Chronic myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) have an inherent tendency to progress to acute myeloid leukemia (AML). Using high-resolution SNP microarrays, we studied a total of 517 MPN and MDS patients in different disease stages, including 77 AML cases with previous history of MPN (N = 46) or MDS (N = 31). Frequent chromosomal deletions of variable sizes were detected, allowing the mapping of putative tumor suppressor genes involved in the leukemic transformation process. We detected frequent deletions on the short arm of chromosome 6 (del6p). The common deleted region on 6p mapped to a 1.1-Mb region and contained only the JARID2 genemember of the polycomb repressive complex 2 (PRC2). When we compared the frequency of del6p between chronic and leukemic phase, we observed a strong association of del6p with leukemic transformation (P = 0.0033). Subsequently, analysis of deletion profiles of other PRC2 members revealed frequent losses of genes such as EZH2, AEBP2, and SUZ12; however, the deletions targeting these genes were large. We also identified two patients with homozygous losses of JARID2 and AEBP2. We observed frequent codeletion of AEBP2 and ETV6, and similarly, SUZ12 and NF1. Using next generation exome sequencing of 40 patients, we identified only one somatic mutation in the PRC2 complex member SUZ12. As the frequency of point mutations in PRC2 members was found to be low, deletions were the main type of lesions targeting PRC2 complex members. Our study suggests an essential role of the PRC2 complex in the leukemic transformation of chronic myeloid disorders. Am. J. Hematol. 2012.", publisher = "Wiley, Hoboken", journal = "American Journal of Hematology", title = "Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies", pages = "250-245", number = "3", volume = "87", doi = "10.1002/ajh.22257" }
Puda, A., Milosević, J. D., Berg, T., Klampfl, T., Harutyunyan, A. S., Gisslinger, B., Rumi, E., Pietra, D., Malcovati, L., Elena, C., Doubek, M., Steurer, M., Tošić, N., Pavlović, S., Guglielmelli, P., Pieri, L., Vannucchi, A. M., Gisslinger, H., Cazzola, M.,& Kralovics, R.. (2012). Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies. in American Journal of Hematology Wiley, Hoboken., 87(3), 245-250. https://doi.org/10.1002/ajh.22257
Puda A, Milosević JD, Berg T, Klampfl T, Harutyunyan AS, Gisslinger B, Rumi E, Pietra D, Malcovati L, Elena C, Doubek M, Steurer M, Tošić N, Pavlović S, Guglielmelli P, Pieri L, Vannucchi AM, Gisslinger H, Cazzola M, Kralovics R. Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies. in American Journal of Hematology. 2012;87(3):245-250. doi:10.1002/ajh.22257 .
Puda, Ana, Milosević, Jelena D., Berg, Tiina, Klampfl, Thorsten, Harutyunyan, Ashot S., Gisslinger, Bettina, Rumi, Elisa, Pietra, Daniela, Malcovati, Luca, Elena, Chiara, Doubek, Michael, Steurer, Michael, Tošić, Nataša, Pavlović, Sonja, Guglielmelli, Paola, Pieri, Lisa, Vannucchi, Alessandro M., Gisslinger, Heinz, Cazzola, Mario, Kralovics, Robert, "Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies" in American Journal of Hematology, 87, no. 3 (2012):245-250, https://doi.org/10.1002/ajh.22257 . .