Multistep pathogenesis of chronic myelomonocytic leukemia in patients.
CMML
NRAS
SRSF2
TET2
pathogenesis
Journal
European journal of haematology
ISSN: 1600-0609
Titre abrégé: Eur J Haematol
Pays: England
ID NLM: 8703985
Informations de publication
Date de publication:
Jul 2022
Jul 2022
Historique:
revised:
09
03
2022
received:
06
01
2022
accepted:
10
03
2022
pubmed:
18
3
2022
medline:
15
6
2022
entrez:
17
3
2022
Statut:
ppublish
Résumé
A multistep pathogenesis of myeloid leukemia including mutations in epigenetic, spliceosome, and signaling genes has been recently demonstrated in a preclinical model but is poorly validated in patients. Clinical, phenotypic, and biologic features were compared between three distinct molecularly defined CMML cohorts including TET2 monomutated patients (T, n = 10), TET2/SRSF2 bimutated patients (TS, n = 19), and patients who had NRAS mutations in addition to TET2/SRSF2 comutations (TSN, n = 14). Median survival was 90, 45, and 9 months, respectively (p = .001). Whereas no patient in the T and TS group transformed into acute myeloid leukemia (AML), 6/14 patients in the TSN group had AML at study entry or transformed during follow-up. Leukocyte counts, blast cell counts, and LDH levels were significantly higher in TSN vs. TS and T, respectively, whereas hemoglobin and platelet values were not significantly different. Increased growth factor-independent myeloid colony formation was restricted to TSN but not found in T and TS, respectively. The proportion of patients showing in vitro myelomonocytic skewing in T, TS, and TSN was 0%, 56%, and 100%, respectively (p = .010). Our results demonstrate that the model of multistep pathogenesis in CMML can be recapitulated in patients regarding clinical, phenotypic, and biologic features.
Sections du résumé
BACKGROUND
BACKGROUND
A multistep pathogenesis of myeloid leukemia including mutations in epigenetic, spliceosome, and signaling genes has been recently demonstrated in a preclinical model but is poorly validated in patients.
METHODS
METHODS
Clinical, phenotypic, and biologic features were compared between three distinct molecularly defined CMML cohorts including TET2 monomutated patients (T, n = 10), TET2/SRSF2 bimutated patients (TS, n = 19), and patients who had NRAS mutations in addition to TET2/SRSF2 comutations (TSN, n = 14).
RESULTS
RESULTS
Median survival was 90, 45, and 9 months, respectively (p = .001). Whereas no patient in the T and TS group transformed into acute myeloid leukemia (AML), 6/14 patients in the TSN group had AML at study entry or transformed during follow-up. Leukocyte counts, blast cell counts, and LDH levels were significantly higher in TSN vs. TS and T, respectively, whereas hemoglobin and platelet values were not significantly different. Increased growth factor-independent myeloid colony formation was restricted to TSN but not found in T and TS, respectively. The proportion of patients showing in vitro myelomonocytic skewing in T, TS, and TSN was 0%, 56%, and 100%, respectively (p = .010).
CONCLUSION
CONCLUSIONS
Our results demonstrate that the model of multistep pathogenesis in CMML can be recapitulated in patients regarding clinical, phenotypic, and biologic features.
Identifiants
pubmed: 35299281
doi: 10.1111/ejh.13768
pmc: PMC9310570
doi:
Substances chimiques
Biological Products
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
50-57Subventions
Organisme : Gesellschaft zur Erforschung der Biologie und Therapie von Tumorkrankheiten
ID : ABCMML-112015
Informations de copyright
© 2022 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.
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