The Impact of Inflammation-Induced Tumor Plasticity during Myeloid Transformation.
Journal
Cancer discovery
ISSN: 2159-8290
Titre abrégé: Cancer Discov
Pays: United States
ID NLM: 101561693
Informations de publication
Date de publication:
05 10 2022
05 10 2022
Historique:
received:
25
08
2021
revised:
26
05
2022
accepted:
01
08
2022
pubmed:
5
8
2022
medline:
7
10
2022
entrez:
4
8
2022
Statut:
ppublish
Résumé
Clonal hematopoiesis (CH) is an aging-associated condition characterized by the clonal outgrowth of mutated preleukemic cells. Individuals with CH are at an increased risk of developing hematopoietic malignancies. Here, we describe a novel animal model carrying a recurrent TET2 missense mutation frequently found in patients with CH and leukemia. In a fashion similar to CH, animals show signs of disease late in life when they develop a wide range of myeloid neoplasms, including acute myeloid leukemia (AML). Using single-cell transcriptomic profiling of the bone marrow, we show that disease progression in aged animals correlates with an enhanced inflammatory response and the emergence of an aberrant inflammatory monocytic cell population. The gene signature characteristic of this inflammatory population is associated with poor prognosis in patients with AML. Our study illustrates an example of collaboration between a genetic lesion found in CH and inflammation, leading to transformation and the establishment of blood neoplasms. Progression from a preleukemic state to transformation, in the presence of TET2 mutations, is coupled with the emergence of inflammation and a novel population of inflammatory monocytes. Genes characteristic of this inflammatory population are associated with the worst prognosis in patients with AML. These studies connect inflammation to progression to leukemia. See related commentary by Pietras and DeGregori, p. 2234 . This article is highlighted in the In This Issue feature, p. 2221.
Identifiants
pubmed: 35924979
pii: 707436
doi: 10.1158/2159-8290.CD-21-1146
pmc: PMC9547930
mid: NIHMS1829543
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2392-2413Subventions
Organisme : NCI NIH HHS
ID : R01 CA173636
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016087
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA196171
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA228135
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA216421
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK121831
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA266212
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL159175
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA260028
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA242020
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016058
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180882
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA271455
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA252239
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL135787
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA229086
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM108583
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180821
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
©2022 American Association for Cancer Research.
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