Journal
CANCER DISCOVERY
Volume 12, Issue 10, Pages 2392-2413Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-21-1146
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Funding
- Cancer Center Support Grant at the Laura and Isaac Perlmutter Cancer Center [P30CA016087]
- NYU Histology Core [5P30CA16087-31]
- NIH [R01GM108583]
- NCI/NIH [R01CA260028-01, P01CA229086, R01CA252239-01, RO1CA216421, RO1CA173636, RO1CA228135, RO1CA242020, RO1HL159175, RO1CA271455]
- Pelotonia
- American Society of Hematology
- Leukemia & Lymphoma Society (LLS)
- Leukemia Research Foundation
- Ramon Areces Foundation
- American Society of Hematology (ASH Restart Research Award)
- EvansMDS Foundation
- LLS
- Alliance for Clinical Trials in Oncology [U10CA180821, U10CA180882, U24CA196171]
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This article describes a novel animal model carrying a recurrent TET2 missense mutation frequently found in patients with CH and leukemia. Using single-cell transcriptomic profiling of the bone marrow, the study showed that disease progression in aged animals correlates with an enhanced inflammatory response and the emergence of an aberrant inflammatory monocytic cell population.
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 carry-ing 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 profi ling of the bone marrow, we show that disease progression in aged animals correlates with an enhanced infl am-matory response and the emergence of an aberrant infl ammatory monocytic cell population. The gene signature characteristic of this infl ammatory 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 infl ammation, leading to transformation and the establishment of blood neoplasms.
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