Clonal Hematopoiesis Before, During, and After Human Spaceflight

Mencia-Trinchant, Nuria; MacKay, Matthew; Chin, Christopher R.; Afshinnekoo, Ebrahim; Foox, Jonathan; Meydan, Cem; Butler, Daniel; Mozsary, Christopher; Vernice, Nicholas A.; Darby, Charlotte A.; Schatz, Michael C.; Bailey, Susan M.; Melnick, Ari; Guzmán, Mónica L.; Bolton, Kelly L.; Braunstein, Lior Z.; Garrett-Bakelman, Francine E.; Levine, Ross L.; Hassane, Duane C.; Mason, Christopher E.

doi:10.1016/j.celrep.2020.108458

Cited by 45 publications

(27 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Occupational exposures to ionizing radiation, such as nuclear power generation or space travel, may predispose individuals to development and evolution of clonal hematopoiesis, which has been identified as a risk factor for myeloid neoplasm. 52,53 Our study has limitations, because it is a retrospective, single-center analysis spanning several decades during which RT techniques and treatment of myeloid malignancies have evolved. Specific data pertaining to radiation doses and fields were not uniformly available.…”

Section: Discussionmentioning

confidence: 99%

Therapy-Related Myeloid Neoplasms in 109 Patients Following Radiation Monotherapy

et al. 2021

View full text Add to dashboard Cite

Therapy-related myeloid neoplasms (t-MNs) are a late complication of cytotoxic therapy and are defined as a distinct entity by the World Health Organization. While the link between chemotherapy exposure and risk of subsequent t-MN is well-described, the association between radiation monotherapy (RT) and t-MN risk is less definitive. We analyzed 109 consecutive patients who developed t-MNs after RT and describe latencies, cytogenetic profile, mutation analyses, and clinical outcomes. The most common cytogenetic abnormality was a clonal abnormality in chromosome 5 and/or 7, which was present in 45% of patients. The median latency from RT to t-MN diagnosis was 6.5 years, with the shortest latency in patients with balanced translocations. 1-year overall survival (OS) was 52% and 5-year OS was 22% for the entire cohort. Patients with chromosome 5 and/or 7 abnormalities experienced worse 1-year OS (37%) and 5-year OS (2%) when compared to other cytogenetic groups (p<0.0001). 16 patients underwent NGS; ASXL1 and TET2 were the most commonly mutated genes (n=4). In addition, 17 patients underwent germline variant testing and 3 carried pathogenic or likely pathogenic germline variants. In conclusion, patients with t-MN after RT monotherapy have increased frequencies of chromosome 5 and/or 7 abnormalities, which are associated with poor overall survival. In addition, pathogenic germline variants may be common in patients with t-MN after RT monotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Therapy-Related Myeloid Neoplasms in 109 Patients Following Radiation Monotherapy

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Consistent with our previous works and proposition that inversions are particularly informative biomarkers of exposure to high LET and space radiations (Garrett-Bakelman et al, 2019;McKenna et al, 2019;Ray et al, 2014), inversions were significantly increased during spaceflight for all three astronauts ( Figure 5B). Furthermore, increased frequencies of inversions persisted after spaceflight for all three crewmembers, potentially suggestive of stem cell damage, clonal hematopoiesis (growth advantage), and/or instability (Garrett-Bakelman et al, 2019;Trinchant, 2020). Satellite associations of acrocentric chromosomes have been proposed as early biomarkers of chronic exposure to low levels of ionizing radiation in occupationally exposed hospital workers (Caradonna, 2015).…”

Section: Chronic Space Radiation Exposurementioning

confidence: 99%

Temporal Telomere and DNA Damage Responses in the Space Radiation Environment

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…These studies provide new insights into the environment of outer space, including radiation and microgravity, and the way it affects biological and physiological states. [231][232][233][234] Support from the aerospace agency will continue to help uncover more solid, physiologically accurate findings on skeletal mechanobiology.…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Mechanical regulation of bone remodeling

et al. 2022

View full text Add to dashboard Cite

Bone remodeling is a lifelong process that gives rise to a mature, dynamic bone structure via a balance between bone formation by osteoblasts and resorption by osteoclasts. These opposite processes allow the accommodation of bones to dynamic mechanical forces, altering bone mass in response to changing conditions. Mechanical forces are indispensable for bone homeostasis; skeletal formation, resorption, and adaptation are dependent on mechanical signals, and loss of mechanical stimulation can therefore significantly weaken the bone structure, causing disuse osteoporosis and increasing the risk of fracture. The exact mechanisms by which the body senses and transduces mechanical forces to regulate bone remodeling have long been an active area of study among researchers and clinicians. Such research will lead to a deeper understanding of bone disorders and identify new strategies for skeletal rejuvenation. Here, we will discuss the mechanical properties, mechanosensitive cell populations, and mechanotransducive signaling pathways of the skeletal system.

show abstract

Clonal Hematopoiesis Before, During, and After Human Spaceflight

Cited by 45 publications

References 40 publications

Therapy-Related Myeloid Neoplasms in 109 Patients Following Radiation Monotherapy

Therapy-Related Myeloid Neoplasms in 109 Patients Following Radiation Monotherapy

Temporal Telomere and DNA Damage Responses in the Space Radiation Environment

Mechanical regulation of bone remodeling

Contact Info

Product

Resources

About