TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups
Risk stratification is critical in the care of patients with myelodysplastic syndromes (MDS). Approximately 10% have a complex karyotype (CK), defined as more than two cytogenetic abnormalities, which is a highly adverse prognostic marker. However, CK-MDS can carry a wide range of chromosomal abnorm...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2019
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| _version_ | 1826302887879245824 |
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| author | Haase, D Stevenson, KE Neuberg, D Maciejewski, JP Nazha, A Sekeres, MA Ebert, BL Garcia-Manero, G Haferlach, C Haferlach, T Kern, W Ogawa, S Nagata, Y Yoshida, K Graubert, TA Walter, MJ List, AF Komrokji, RS Padron, E Sallman, D Papaemmanuil, E Campbell, PJ Savona, MR Seegmiller, A Adès, L Fenaux, P Shih, L-Y Bowen, D Groves, MJ Tauro, S Fontenay, M Kosmider, O Bar-Natan, M Steensma, D Stone, R Heuser, M Thol, F Cazzola, M Malcovati, L Karsan, A Ganster, C Hellström-Lindberg, E Boultwood, J Pellagatti, A Santini, V Quek, L Vyas, P Tüchler, H Greenberg, PL Bejar, R International Working Group For Mds Molecular Prognostic Committee |
| author_facet | Haase, D Stevenson, KE Neuberg, D Maciejewski, JP Nazha, A Sekeres, MA Ebert, BL Garcia-Manero, G Haferlach, C Haferlach, T Kern, W Ogawa, S Nagata, Y Yoshida, K Graubert, TA Walter, MJ List, AF Komrokji, RS Padron, E Sallman, D Papaemmanuil, E Campbell, PJ Savona, MR Seegmiller, A Adès, L Fenaux, P Shih, L-Y Bowen, D Groves, MJ Tauro, S Fontenay, M Kosmider, O Bar-Natan, M Steensma, D Stone, R Heuser, M Thol, F Cazzola, M Malcovati, L Karsan, A Ganster, C Hellström-Lindberg, E Boultwood, J Pellagatti, A Santini, V Quek, L Vyas, P Tüchler, H Greenberg, PL Bejar, R International Working Group For Mds Molecular Prognostic Committee |
| author_sort | Haase, D |
| collection | OXFORD |
| description | Risk stratification is critical in the care of patients with myelodysplastic syndromes (MDS). Approximately 10% have a complex karyotype (CK), defined as more than two cytogenetic abnormalities, which is a highly adverse prognostic marker. However, CK-MDS can carry a wide range of chromosomal abnormalities and somatic mutations. To refine risk stratification of CK-MDS patients, we examined data from 359 CK-MDS patients shared by the International Working Group for MDS. Mutations were underrepresented with the exception of TP53 mutations, identified in 55% of patients. TP53 mutated patients had even fewer co-mutated genes but were enriched for the del(5q) chromosomal abnormality (p < 0.005), monosomal karyotype (p < 0.001), and high complexity, defined as more than 4 cytogenetic abnormalities (p < 0.001). Monosomal karyotype, high complexity, and TP53 mutation were individually associated with shorter overall survival, but monosomal status was not significant in a multivariable model. Multivariable survival modeling identified severe anemia (hemoglobin < 8.0 g/dL), NRAS mutation, SF3B1 mutation, TP53 mutation, elevated blast percentage (>10%), abnormal 3q, abnormal 9, and monosomy 7 as having the greatest survival risk. The poor risk associated with CK-MDS is driven by its association with prognostically adverse TP53 mutations and can be refined by considering clinical and karyotype features. |
| first_indexed | 2024-03-07T05:54:16Z |
| format | Journal article |
| id | oxford-uuid:e9f86a5f-8ced-4bb7-944f-fa27fc2c2541 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:54:16Z |
| publishDate | 2019 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:e9f86a5f-8ced-4bb7-944f-fa27fc2c25412022-03-27T10:58:23ZTP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroupsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e9f86a5f-8ced-4bb7-944f-fa27fc2c2541EnglishSymplectic Elements at OxfordSpringer Nature2019Haase, DStevenson, KENeuberg, DMaciejewski, JPNazha, ASekeres, MAEbert, BLGarcia-Manero, GHaferlach, CHaferlach, TKern, WOgawa, SNagata, YYoshida, KGraubert, TAWalter, MJList, AFKomrokji, RSPadron, ESallman, DPapaemmanuil, ECampbell, PJSavona, MRSeegmiller, AAdès, LFenaux, PShih, L-YBowen, DGroves, MJTauro, SFontenay, MKosmider, OBar-Natan, MSteensma, DStone, RHeuser, MThol, FCazzola, MMalcovati, LKarsan, AGanster, CHellström-Lindberg, EBoultwood, JPellagatti, ASantini, VQuek, LVyas, PTüchler, HGreenberg, PLBejar, RInternational Working Group For Mds Molecular Prognostic CommitteeRisk stratification is critical in the care of patients with myelodysplastic syndromes (MDS). Approximately 10% have a complex karyotype (CK), defined as more than two cytogenetic abnormalities, which is a highly adverse prognostic marker. However, CK-MDS can carry a wide range of chromosomal abnormalities and somatic mutations. To refine risk stratification of CK-MDS patients, we examined data from 359 CK-MDS patients shared by the International Working Group for MDS. Mutations were underrepresented with the exception of TP53 mutations, identified in 55% of patients. TP53 mutated patients had even fewer co-mutated genes but were enriched for the del(5q) chromosomal abnormality (p < 0.005), monosomal karyotype (p < 0.001), and high complexity, defined as more than 4 cytogenetic abnormalities (p < 0.001). Monosomal karyotype, high complexity, and TP53 mutation were individually associated with shorter overall survival, but monosomal status was not significant in a multivariable model. Multivariable survival modeling identified severe anemia (hemoglobin < 8.0 g/dL), NRAS mutation, SF3B1 mutation, TP53 mutation, elevated blast percentage (>10%), abnormal 3q, abnormal 9, and monosomy 7 as having the greatest survival risk. The poor risk associated with CK-MDS is driven by its association with prognostically adverse TP53 mutations and can be refined by considering clinical and karyotype features. |
| spellingShingle | Haase, D Stevenson, KE Neuberg, D Maciejewski, JP Nazha, A Sekeres, MA Ebert, BL Garcia-Manero, G Haferlach, C Haferlach, T Kern, W Ogawa, S Nagata, Y Yoshida, K Graubert, TA Walter, MJ List, AF Komrokji, RS Padron, E Sallman, D Papaemmanuil, E Campbell, PJ Savona, MR Seegmiller, A Adès, L Fenaux, P Shih, L-Y Bowen, D Groves, MJ Tauro, S Fontenay, M Kosmider, O Bar-Natan, M Steensma, D Stone, R Heuser, M Thol, F Cazzola, M Malcovati, L Karsan, A Ganster, C Hellström-Lindberg, E Boultwood, J Pellagatti, A Santini, V Quek, L Vyas, P Tüchler, H Greenberg, PL Bejar, R International Working Group For Mds Molecular Prognostic Committee TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups |
| title | TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups |
| title_full | TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups |
| title_fullStr | TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups |
| title_full_unstemmed | TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups |
| title_short | TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups |
| title_sort | tp53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups |
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