Clinical, molecular, and prognostic correlates of number, type, and functional localization of TET2 mutations in chronic myelomonocytic leukemia (CMML)-a study of 1084 patients
Loss-of-function TET2 mutations (TET2MT) are frequent early clonal events in myeloid neoplasms and are thought to confer a fitness advantage to hematopoietic precursors. This large, multi-institutional study (n = 1084), investigated the TET2 mutational landscape and prognostic implications of the number, type, and location of TET2MT and the epistatic relationship with other somatic events in chronic myelomonocytic leukemia (CMML). Nine hundred and forty-two TET2MT were identified in 604 (56%) patients, of which 710 (75%) were predicted to be truncating (involving the catalytic domain). Three hundred and sixteen (29%) patients had ≥1 TET2MT, with 28%, 1%, and 0.2% harboring 2, 3, and 5 mutations, respectively. In comparison to TET2WT, TET2MT patients were older in age, more likely to have dysplastic CMML, a higher number of co-occurring mutations, and lower-risk stratification. Importantly, TET2MT were associated with a survival advantage (49 vs. 30 months, p < 0.0001), especially in the context of multiple TET2MT (≥2; 57 months, p < 0.001), and truncating TET2MT (51 months, p < 0.001). In addition, the adverse prognostic impact of ASXL1MT was partially mitigated by concurrent TET2MT, with the ASXL1WT/TET2MT genotype having better outcomes and resulting in further risk stratification of ASXL1 inclusive CMML prognostic models, in comparison to ASXL1MT alone.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:34 |
|---|---|
| Enthalten in: |
Leukemia - 34(2020), 5 vom: 13. Mai, Seite 1407-1421 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Coltro, Giacomo [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Biomarkers, Tumor |
|---|
| Anmerkungen: |
Date Completed 29.09.2020 Date Revised 21.04.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41375-019-0690-7 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM304379344 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM304379344 | ||
| 003 | DE-627 | ||
| 005 | 20231225114847.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41375-019-0690-7 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1014.xml |
| 035 | |a (DE-627)NLM304379344 | ||
| 035 | |a (NLM)31836856 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Coltro, Giacomo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Clinical, molecular, and prognostic correlates of number, type, and functional localization of TET2 mutations in chronic myelomonocytic leukemia (CMML)-a study of 1084 patients |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 29.09.2020 | ||
| 500 | |a Date Revised 21.04.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Loss-of-function TET2 mutations (TET2MT) are frequent early clonal events in myeloid neoplasms and are thought to confer a fitness advantage to hematopoietic precursors. This large, multi-institutional study (n = 1084), investigated the TET2 mutational landscape and prognostic implications of the number, type, and location of TET2MT and the epistatic relationship with other somatic events in chronic myelomonocytic leukemia (CMML). Nine hundred and forty-two TET2MT were identified in 604 (56%) patients, of which 710 (75%) were predicted to be truncating (involving the catalytic domain). Three hundred and sixteen (29%) patients had ≥1 TET2MT, with 28%, 1%, and 0.2% harboring 2, 3, and 5 mutations, respectively. In comparison to TET2WT, TET2MT patients were older in age, more likely to have dysplastic CMML, a higher number of co-occurring mutations, and lower-risk stratification. Importantly, TET2MT were associated with a survival advantage (49 vs. 30 months, p < 0.0001), especially in the context of multiple TET2MT (≥2; 57 months, p < 0.001), and truncating TET2MT (51 months, p < 0.001). In addition, the adverse prognostic impact of ASXL1MT was partially mitigated by concurrent TET2MT, with the ASXL1WT/TET2MT genotype having better outcomes and resulting in further risk stratification of ASXL1 inclusive CMML prognostic models, in comparison to ASXL1MT alone | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Biomarkers, Tumor |2 NLM | |
| 650 | 7 | |a DNA-Binding Proteins |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins |2 NLM | |
| 650 | 7 | |a Dioxygenases |2 NLM | |
| 650 | 7 | |a EC 1.13.11.- |2 NLM | |
| 650 | 7 | |a TET2 protein, human |2 NLM | |
| 650 | 7 | |a EC 1.13.11.- |2 NLM | |
| 700 | 1 | |a Mangaonkar, Abhishek A |e verfasserin |4 aut | |
| 700 | 1 | |a Lasho, Terra L |e verfasserin |4 aut | |
| 700 | 1 | |a Finke, Christy M |e verfasserin |4 aut | |
| 700 | 1 | |a Pophali, Prateek |e verfasserin |4 aut | |
| 700 | 1 | |a Carr, Ryan |e verfasserin |4 aut | |
| 700 | 1 | |a Gangat, Naseema |e verfasserin |4 aut | |
| 700 | 1 | |a Binder, Moritz |e verfasserin |4 aut | |
| 700 | 1 | |a Pardanani, Animesh |e verfasserin |4 aut | |
| 700 | 1 | |a Fernandez-Zapico, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Robertson, Keith D |e verfasserin |4 aut | |
| 700 | 1 | |a Bosi, Alberto |e verfasserin |4 aut | |
| 700 | 1 | |a Droin, Nathalie |e verfasserin |4 aut | |
| 700 | 1 | |a Vannucchi, Alessandro M |e verfasserin |4 aut | |
| 700 | 1 | |a Tefferi, Ayalew |e verfasserin |4 aut | |
| 700 | 1 | |a Hunter, Anthony |e verfasserin |4 aut | |
| 700 | 1 | |a Padron, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Solary, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Patnaik, Mrinal M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Leukemia |d 1989 |g 34(2020), 5 vom: 13. Mai, Seite 1407-1421 |w (DE-627)NLM012593788 |x 1476-5551 |7 nnns |
| 773 | 1 | 8 | |g volume:34 |g year:2020 |g number:5 |g day:13 |g month:05 |g pages:1407-1421 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41375-019-0690-7 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 34 |j 2020 |e 5 |b 13 |c 05 |h 1407-1421 | ||