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

Burns, Sarah; Kapur, Reuben

doi:10.1016/j.stemcr.2020.07.008

Cited by 12 publications

(10 citation statements)

References 102 publications

(202 reference statements)

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“…Access to the WGS data of the 3668 Dutch metastases cohort from the Hartwig Medical Foundation can be requested at https://www.hartwigmedicalfoundation.nl/en/applying-for-data/ . The CHIP and SCT databases were extracted from the supplemental information of the publications listed in Table 1 of Burns and Kapur (2020) . The normal aging dataset used as control for the RF was extracted from the supplementary table of Lee-Six et al.…”

Section: Methodsmentioning

confidence: 99%

Antiviral treatment causes a unique mutational signature in cancers of transplantation recipients

et al. 2021

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Summary Genetic instability is a major concern for successful application of stem cells in regenerative medicine. However, the mutational consequences of the most applied stem cell therapy in humans, hematopoietic stem cell transplantation (HSCT), remain unknown. Here we characterized the mutation burden of hematopoietic stem and progenitor cells (HSPCs) of human HSCT recipients and their donors using whole-genome sequencing. We demonstrate that the majority of transplanted HSPCs did not display altered mutation accumulation. However, in some HSCT recipients, we identified multiple HSPCs with an increased mutation burden after transplantation. This increase could be attributed to a unique mutational signature caused by the antiviral drug ganciclovir. Using a machine learning approach, we detected this signature in cancer genomes of individuals who received HSCT or solid organ transplantation earlier in life. Antiviral treatment with nucleoside analogs can cause enhanced mutagenicity in transplant recipients, which may ultimately contribute to therapy-related carcinogenesis.

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Section: Methodsmentioning

confidence: 99%

Antiviral treatment causes a unique mutational signature in cancers of transplantation recipients

et al. 2021

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“…Clonal haematopoiesis of indeterminate potential (CHIP) is a common occult condition characterized as expansion of age-acquired somatic mutations in hematopoietic lineages that are associated with tumorigenesis, persistence of measurable residual diseases, disease relapse as well as the development of DCL after HSCT in hematologic malignancies. It is believed that CHIP is a novel risk factor for DCL [27], especially if donor and/or recipient are aging individuals. The patient we report was over 60 years old at the time of her second HSCT.…”

Section: Discussionmentioning

confidence: 99%

Donor Cell-Derived Acute Myeloid Leukaemia with 3q26.2 Involvement/MECOM Rearrangement ‐ A Case Report and Literature Review

Gu¹,

Wang²,

Tang³

et al. 2020

OBM Transplantation

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Donor cell-derived leukaemia (DCL) is an uncommon complication of allogeneic hematopoietic stem cell transplantation (HSCT). DCL might represent up to 5% of the post-HSCT disease relapses, but case numbers reported in the literature might underestimate the frequency. The leukemogenesis of DCL is not well understood due to the limited numbers of cases reported and lack of detailed molecular genetic information from recipients and donors. Although many theories have been proposed for leukemogenesis of DCL, the underlying molecular genetic mechanism are likely heterogeneous. Here we report a case of donor cell-derived acute myeloid leukaemia with 3q26.2 involvement/MECOM rearrangement and chromosome 20q deletion. We also reviewed the literature of previously described DCL cases, and we discussed the risk factors that might be important to the onset of DCL.

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“…Age-Related Clonal Hematopoiesis CHIP, also known as age-related clonal hematopoiesis (ARCH), is characterized by expansion of somatic mutations in various hematopoietic lineages of older persons and is associated with risks of developing leukemia [43], as well as other age-associated disorders including cardiovascular disease [44]. Human aging is associated with an exponential increase in the occurrence of CHIP in aged individuals.…”

Section: C) Age-related Clonal Hematopoiesis Of Indeterminant Potential (Chip) and Inflammationmentioning

confidence: 99%

“…Human aging is associated with an exponential increase in the occurrence of CHIP in aged individuals. It is an emerging public health issue that affects at least 15-20% of individuals aged 70 or above [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59]. A number of reviews and reports on clonal hematopoiesis have been published [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59].…”

Section: C) Age-related Clonal Hematopoiesis Of Indeterminant Potential (Chip) and Inflammationmentioning

confidence: 99%

“…Several comorbidities with inflammatory components, such as ulcerative colitis, rheumatoid arthritis, and systemic sclerosis, have been linked to increased clonal hematopoiesis [119][120][121]. Proinflammatory features of CHIP-associated HSCs/HPCs may influence outcomes of hematopoietic stem cell transplants, leading to cytopenias, chronic graft vs. host disease, and/or donor-derived leukemia (DDL) [122]. These patient populations may especially be vulnerable to development of hematological malignancies and CHIP-associated diseases following infection, as infection may exacerbate the existing inflammatory response in these patients.…”

Section: Inflammationmentioning

confidence: 99%

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Fate of Hematopoiesis During Aging. What Do We Really Know, and What are its Implications?

Broxmeyer

Liu

Kapur

et al. 2020

Stem Cell Rev and Rep

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There is an ongoing shift in demographics such that older persons will outnumber young persons in the coming years, and with it age-associated tissue attrition and increased diseases and disorders. There has been increased information on the association of the aging process with dysregulation of hematopoietic stem (HSC) and progenitor (HPC) cells, and hematopoiesis. This review provides an extensive up-to date summary on the literature of aged hematopoiesis and HSCs placed in context of potential artifacts of the collection and processing procedure, that may not be totally representative of the status of HSCs in their in vivo bone marrow microenvironment, and what the implications of this are for understanding aged hematopoiesis. This review covers a number of interactive areas, many of which have not been adequately explored. There are still many unknowns and mechanistic insights to be elucidated to better understand effects of aging on the hematopoietic system, efforts that will take multidisciplinary approaches, and that could lead to means to ameliorate at least some of the dysregulation of HSCs and HPCs associated with the aging process. Graphical Abstract

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

Cited by 12 publications

References 102 publications

Antiviral treatment causes a unique mutational signature in cancers of transplantation recipients

Antiviral treatment causes a unique mutational signature in cancers of transplantation recipients

Donor Cell-Derived Acute Myeloid Leukaemia with 3q26.2 Involvement/MECOM Rearrangement ‐ A Case Report and Literature Review

Fate of Hematopoiesis During Aging. What Do We Really Know, and What are its Implications?

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