Prognostic impact of DDX41 germline mutations in intensively treated acute myeloid leukemia patients: an ALFA-FILO study.
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
18 08 2022
18 08 2022
Historique:
received:
07
01
2022
accepted:
01
04
2022
pubmed:
21
4
2022
medline:
23
8
2022
entrez:
20
4
2022
Statut:
ppublish
Résumé
DDX41 germline mutations (DDX41MutGL) are the most common genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia (AML). Recent reports suggest that DDX41MutGL myeloid malignancies could be considered as a distinct entity, even if their specific presentation and outcome remain to be defined. We describe here the clinical and biological features of 191 patients with DDX41MutGL AML. Baseline characteristics and outcome of 86 of these patients, treated with intensive chemotherapy in 5 prospective Acute Leukemia French Association/French Innovative Leukemia Organization trials, were compared with those of 1604 patients with DDX41 wild-type (DDX41WT) AML, representing a prevalence of 5%. Patients with DDX41MutGL AML were mostly male (75%), in their seventh decade, and with low leukocyte count (median, 2 × 109/L), low bone marrow blast infiltration (median, 33%), normal cytogenetics (75%), and few additional somatic mutations (median, 2). A second somatic DDX41 mutation (DDX41MutSom) was found in 82% of patients, and clonal architecture inference suggested that it could be the main driver for AML progression. DDX41MutGL patients displayed higher complete remission rates (94% vs 69%; P < .0001) and longer restricted mean overall survival censored at hematopoietic stem cell transplantation (HSCT) than 2017 European LeukemiaNet intermediate/adverse (Int/Adv) DDX41WT patients (5-year difference in restricted mean survival times, 13.6 months; P < .001). Relapse rates censored at HSCT were lower at 1 year in DDX41MutGL patients (15% vs 44%) but later increased to be similar to Int/Adv DDX41WT patients at 3 years (82% vs 75%). HSCT in first complete remission was associated with prolonged relapse-free survival (hazard ratio, 0.43; 95% confidence interval, 0.21-0.88; P = .02) but not with longer overall survival (hazard ratio, 0.77; 95% confidence interval, 0.35-1.68; P = .5).
Identifiants
pubmed: 35443031
pii: S0006-4971(22)00549-3
doi: 10.1182/blood.2021015328
pmc: PMC9389637
doi:
Substances chimiques
DDX41 protein, human
EC 3.6.1.-
DEAD-box RNA Helicases
EC 3.6.4.13
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
756-768Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022 by The American Society of Hematology.
Références
Leukemia. 2016 Oct;30(10):2083-2086
pubmed: 27133828
Blood. 2021 Aug 19;138(7):507-519
pubmed: 34410352
Cell Stem Cell. 2021 Nov 4;28(11):1966-1981.e6
pubmed: 34473945
Leukemia. 2018 Jul;32(7):1482-1492
pubmed: 29483711
Blood. 2020 Feb 20;135(8):542-546
pubmed: 31880804
Blood. 2022 Feb 24;139(8):1208-1221
pubmed: 34482403
J Clin Oncol. 2017 Apr 10;35(11):1223-1230
pubmed: 28221862
Curr Opin Hematol. 2021 Mar 1;28(2):86-93
pubmed: 33394724
Cancer Cell. 2015 May 11;27(5):658-70
pubmed: 25920683
Dev Cell. 2021 Mar 8;56(5):627-640.e5
pubmed: 33651979
Br J Haematol. 2021 Mar;192(6):1006-1010
pubmed: 32307695
J Mol Diagn. 2007 Feb;9(1):1-6
pubmed: 17251329
Blood Adv. 2022 Jan 25;6(2):528-532
pubmed: 34644397
Front Oncol. 2021 Jan 28;10:582213
pubmed: 33585199
Nat Rev Cancer. 2021 Feb;21(2):122-137
pubmed: 33328584
Blood. 2016 Feb 25;127(8):1017-23
pubmed: 26712909
Semin Hematol. 2017 Apr;54(2):87-93
pubmed: 28637622
Haematologica. 2022 Feb 01;107(2):510-518
pubmed: 33626862
Hemasphere. 2021 Mar 23;5(4):e552
pubmed: 33778416
Nat Immunol. 2011 Sep 04;12(10):959-65
pubmed: 21892174
Protein Cell. 2017 Feb;8(2):83-89
pubmed: 27502187
J Clin Oncol. 2018 Nov 10;36(32):3203-3210
pubmed: 30260758
Int J Hematol. 2020 Feb;111(2):241-246
pubmed: 31713024
Leukemia. 2017 Apr;31(4):1020-1022
pubmed: 28194039
Leukemia. 2022 Mar;36(3):664-674
pubmed: 34671111
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Blood Adv. 2020 May 12;4(9):1942-1949
pubmed: 32380535
Cancer Discov. 2021 May;11(5):1082-1099
pubmed: 33408242
Blood. 2016 May 19;127(20):2391-405
pubmed: 27069254
Am J Hematol. 2020 Feb;95(2):227-229
pubmed: 31400013
Leukemia. 2021 May;35(5):1291-1300
pubmed: 32943750
Blood. 2017 Jan 26;129(4):424-447
pubmed: 27895058
Lancet. 2012 Apr 21;379(9825):1508-16
pubmed: 22482940
J Clin Oncol. 2014 Aug 1;32(22):2380-5
pubmed: 24982461
Leukemia. 2016 Dec;30(12):2405-2409
pubmed: 27560106
Leukemia. 2017 Feb;31(2):520-522
pubmed: 27795557
Blood. 2021 Jan 28;137(4):524-532
pubmed: 32871585
Cell Syst. 2019 Jun 26;8(6):514-522.e5
pubmed: 31229560
Blood. 2019 Oct 24;134(17):1441-1444
pubmed: 31484648
Nucleic Acids Res. 2016 Jun 20;44(11):e108
pubmed: 27060149
Am J Hematol. 2019 Jul;94(7):757-766
pubmed: 30963592
Blood Adv. 2018 Jan 23;2(2):146-150
pubmed: 29365323