Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant

Mouhieddine, Tarek H.; Sperling, Adam S.; Redd, Robert A.; Park, Jihye; Leventhal, Matthew; Gibson, Christopher J.; Manier, Salomon; Nassar, Amin H.; Capelletti, Marzia; Huynh, Daisy; Bustoros, Mark; Sklavenitis-Pistofidis, Romanos; Tahri, Sabrin; Hornburg, Kalvis; Dumke, Henry; Itani, Mohamad I.; Boehner, Cody J.; Liu, Chia Jen; AlDubayan, Saud H.; Reardon, Brendan; Allen, Eliezer M. Van; Keats, Jonathan J.; Stewart, Chip; Mehr, Shaadi; Auclair, Daniel; Schlossman, Robert; Munshi, Nikhil C.; Anderson, Kenneth C.; Steensma, David P.; Laubach, Jacob P.; Richardson, Paul G.; Ritz, Jérôme; Ebert, Benjamin L.; Soiffer, Robert J.; Trippa, Lorenzo; Getz, Gad; Neuberg, Donna; Ghobrial, Irène M.

doi:10.1038/s41467-020-16805-5

Cited by 107 publications

(91 citation statements)

References 62 publications

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“…The increased occurrence of clonal haematopoiesis is one of the signs of haematopoietic ageing ( Arends et al, 2018 ; Jaiswal et al, 2014 ). Several studies have investigated the impact of clonal haematopoiesis on the outcome of HSC transplantation therapy ( Frick et al, 2019 ; Gibson et al, 2017 ; Mouhieddine et al, 2020 ; Ortmann et al, 2019 ). However, the implications of clonal haematopoiesis for stem cell transplantation are difficult to identify owing to the high degree of mutational heterogeneity present within the genetically distinct subclones ( Park et al, 2019 ).…”

Section: Hsc Transplantation At Single-cell Resolutionmentioning

confidence: 99%

Haematopoietic ageing through the lens of single-cell technologies

Strzelecka

Damm

2021

Disease Models &Amp; Mechanisms

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Human lifespan is now longer than ever and, as a result, modern society is getting older. Despite that, the detailed mechanisms behind the ageing process and its impact on various tissues and organs remain obscure. In general, changes in DNA, RNA and protein structure throughout life impair their function. Haematopoietic ageing refers to the age-related changes affecting a haematopoietic system. Aged blood cells display different functional aberrations depending on their cell type, which might lead to the development of haematologic disorders, including leukaemias, anaemia or declining immunity. In contrast to traditional bulk assays, which are not suitable to dissect cell-to-cell variation, single-cell-level analysis provides unprecedented insight into the dynamics of age-associated changes in blood. In this Review, we summarise recent studies that dissect haematopoietic ageing at the single-cell level. We discuss what cellular changes occur during haematopoietic ageing at the genomic, transcriptomic, epigenomic and metabolomic level, and provide an overview of the benefits of investigating those changes with single-cell precision. We conclude by considering the potential clinical applications of single-cell techniques in geriatric haematology, focusing on the impact on haematopoietic stem cell transplantation in the elderly and infection studies, including recent COVID-19 research.

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Section: Hsc Transplantation At Single-cell Resolutionmentioning

confidence: 99%

Haematopoietic ageing through the lens of single-cell technologies

Strzelecka

Damm

2021

Disease Models &Amp; Mechanisms

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“…Potentially clonal hematopoiesis may co-exist with MGUS [95]. Recent studies on the presence of CHIP in MM report a prevalence of 22% [96]. Whether this extends to MGUS and correlates with the risk of CVD is not known.…”

Section: Cardiovascular Disease In Mgusmentioning

confidence: 99%

Monoclonal Gammopathy of Undetermined Significance (MGUS)—Not So Asymptomatic after All

Lomas

Mouhieddine

Tahri

et al. 2020

Cancers

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Monoclonal Gammopathy of Undetermined Significance (MGUS) is considered to be a benign precursor condition that may progress to a lymphoproliferative disease or multiple myeloma. Most patients do not progress to an overt condition, but nevertheless, MGUS is associated with a shortened life expectancy and, in a minority of cases, a number of co-morbid conditions that include an increased fracture risk, renal impairment, peripheral neuropathy, secondary immunodeficiency, and cardiovascular disease. This review aims to consolidate current evidence for the significance of these co-morbidities before considering how best to approach these symptoms and signs, which are often encountered in primary care or within a number of specialties in secondary care.

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“…Surprisingly, mutations in other CHIP-associated genes, such as DNMT3A , TET2 , and ASXL1 , were observed but were not associated with inferior outcomes, implying that specific CHIP-associated mutations may be more susceptible to the autologous transplant environment ( Husby et al., 2020 ). Similarly, in patients undergoing autologous transplantation for multiple myeloma, CHIP correlated with decreased survival and increased multiple myeloma progression, indicating that CHIP can modulate multiple types of hematological malignancy ( Mouhieddine et al., 2020 ). Autologous transplantation in CHIP patients is also associated with late non-relapse mortality, demonstrating that CHIP-associated mutations have diverse effects on transplant outcomes ( Slavin et al., 2019 ).…”

Section: Main Textmentioning

confidence: 99%

“… Patients with mutations in DNA damage repair genes exhibited worse overall survival and increased intensive care admissions. Mouhieddine et al. (2020) 629 multiple myeloma patients 58 years autologous 21 CHIP patients developed MDS or AML after transplant.…”

Section: Main Textmentioning

confidence: 99%

Clonal Hematopoiesis of Indeterminate Potential as a Novel Risk Factor for Donor-Derived Leukemia

Burns

Kapur

2020

Stem Cell Reports

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Hematopoietic stem cell transplantation (HSCT) is a critical treatment modality for many hematological and non-hematological diseases that is being extended to treat older individuals. However, recent studies show that clonal hematopoiesis of indeterminate potential (CHIP), a common, asymptomatic condition characterized by the expansion of age-acquired somatic mutations in blood cell lineages, may be a risk factor for the development of donor-derived leukemia (DDL), unexplained cytopenias, and chronic graft-versus-host disease. CHIP may contribute to the pathogenesis of these significant transplant complications via various cell-autonomous and non-cell-autonomous mechanisms, and the clinical presentation of DDL may be broader than anticipated. A more comprehensive understanding of the contributions of CHIP to DDL may have important implications for the screening of donors and will improve the safety of HSCT. The objective of this review is to discuss studies linking DDL and CHIP and to explore potential mechanisms by which CHIP may contribute to DDL.

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Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant

Cited by 107 publications

References 62 publications

Haematopoietic ageing through the lens of single-cell technologies

Haematopoietic ageing through the lens of single-cell technologies

Monoclonal Gammopathy of Undetermined Significance (MGUS)—Not So Asymptomatic after All

Clonal Hematopoiesis of Indeterminate Potential as a Novel Risk Factor for Donor-Derived Leukemia

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