Germline mutations in the bone marrow microenvironment and dysregulated hematopoiesis

Miller, Lane H.; Qu, Cheng‐Kui; Pauly, Melinda

doi:10.1016/j.exphem.2018.07.001

Cited by 15 publications

(13 citation statements)

References 86 publications

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“…Just alike mutations in DDR genes, which are associated with hereditary predispositions to various cancers, the polymorphism of stroma components, may as well define the constitutive permissiveness (predisposition) of tissues for the development of cancer (4). Indeed, the concept of mesenchymal niche-driven oncogenesis has been largely documented in the hematopoietic organs in which multiple cases of association of germline mutations in bone marrow environment with dysregulated hematopoiesis have been reported (9).…”

Section: Introductionmentioning

confidence: 99%

Adipose Tissue Properties in Tumor-Bearing Breasts

et al. 2020

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The tissue stroma plays a major role in tumors' natural history. Most programs for tumor progression are not activated as cell-autonomous processes but under the conditions of cross-talks between tumor and stroma. Adipose tissue is a major component of breast stroma. This study compares adipose tissues in tumor-bearing breasts to those in tumor-free breasts with the intention of defining a signature that could translate into markers of cancer risk. In tumor-bearing breasts, we sampled adipose tissues adjacent to, or distant from the tumor. Parameters studied included: adipocytes size and density, immune cell infiltration, vascularization, secretome and gene expression. Adipose tissues from tumor-bearing breasts, whether adjacent to or distant from the tumor, do not differ from each other by any of these parameters. By contrast, adipose tissues from tumor-bearing breasts have the capacity to secrete twice as much interleukin 8 (IL-8) than those from tumor-free breasts and differentially express a set of 137 genes of which a significant fraction belongs to inflammation, integrin and wnt signaling pathways. These observations show that adipose tissues from tumor-bearing breasts have a distinct physiological status from those from tumor-free breasts. We propose that this constitutive status contributes as a non-cell autonomous process to determine permissiveness for tumor growth.

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Section: Introductionmentioning

confidence: 99%

Adipose Tissue Properties in Tumor-Bearing Breasts

et al. 2020

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“…Mesenchymal stromal cells (MSCs), which differentiate into adipocytes, osteocytes, and chondrocytes, are a vital part of the stem cell niche. Recently conducted studies have shown that mutated stromal cells, including MSCs, can promote malignant transformation of healthy HSCs . This is an area of ongoing investigation that has tremendous implications for the management of patients with HHMs.…”

Section: Additional Points To Considermentioning

confidence: 99%

When should transplant physicians think about familial blood cancers?

et al. 2019

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Although germline predisposition to hematologic malignancy is gaining increasing recognition and more patients with acute myeloid leukemia and myelodysplastic syndrome may have a germline predisposition than previously thought, individuals and families with these mutations often go unrecognized. Nowhere are the potential consequences of missing an underlying germline predisposition more devastating than in the setting of allogeneic hematopoietic cell transplantation, a procedure often necessary to obtain the best chance of cure for patients with myeloid malignancies.In this brief review, we will discuss the importance of upfront screening all transplant recipients and all prospective donors to mitigate potential disastrous complications if such germline predisposition is overlooked. We will also outline features that should strongly arise suspicion and prompt testing for germline predisposition as well as highlight some of the challenges and barriers to genetic testing for patients with hematologic malignancies. K E Y W O R D Scancer, germline predisposition, hematopoietic cell transplantation, hereditary hematologic malignancy, oncology

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“…DNMT3A, ASXL1, TET2 52,53 or in germline e.g. RUNX1, GATA2, CEBPA, DDX41, ANKRD26 54 . Apart from those genetic markers, FLT3-ITD, FLT3-TKD, NRAS, KRAS, IDH1, IDH2, MLL-PTD and the expression of EVI1 are not recommended to use as a single marker but rather in combination.…”

Section: Molecular Mrdmentioning

confidence: 99%

The Development of Personalized Medicine: Acute Myeloid Leukemia as a Model

Phikulsod¹

2019

Smj

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The term personalized medicine has been employed in widely different contexts and has acquired status as one of the most often used keywords recently. In this review we take it to understand the application of modern diagnostic medicine and therapeutics to patient with the purpose of eradicating disease or alleviating symptoms in a manner, where all actions are based on detailed knowledge of the condition of the individual patient. Applying these concepts should lead to optimization of clinical decision-making and, in its utmost consequence, a substantial decrease in costs incurred for hospitalization and follow-up. The latter is based on the evidence that for many disorders "less but more targeted" will mean improved outcome. Acute myeloid leukemia (AML) is the most common acute leukemia in adults and is a major challenge in terms of diagnosis, care, follow-up and therapy. Thus, in population-based analyses, overall survival is only just exceeding 40% with major reasons for treatment failure. For these reasons, AML has been intensely studied during the recent decades. With the development of multiparametric flow cytometry, it allows us to get an accurate diagnosis and immunophenotypic profiles of AML. In addition, there is now an abundance of knowledge regarding its cytogenetic and molecular background. These enable us to follow the amount of disease down to the minutest quantity with a high resolution of molecular details. Finally, based on knowledge of these variables in the single patient cytoreduction is now being refined to therapies targeted to the molecular changes in the patient.

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Germline mutations in the bone marrow microenvironment and dysregulated hematopoiesis

Cited by 15 publications

References 86 publications

Adipose Tissue Properties in Tumor-Bearing Breasts

Adipose Tissue Properties in Tumor-Bearing Breasts

When should transplant physicians think about familial blood cancers?

The Development of Personalized Medicine: Acute Myeloid Leukemia as a Model

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