P-254 Chromosomal analysis of hematopoietic and stromal progenitor cells in patients with myelodysplastic syndrome (MDS)

Пименова, М А; Кохно, А. В.; Домрачева, Е. В.; Drize, Nina; Манакова, Т. Е.; Коннова, М. Л.; Maltseva, Y.U.; Shishigina, Lubov; Паровичникова, Е Н; Savchenko, V.

doi:10.1016/s0145-2126(13)70301-1

Cited by 2 publications

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“…Thus, MSPCs from MDS and AML patients do not appear to carry the same cytogenetic alterations as the malignant clone, which argues against a common origin of these cells. However, as mentioned above, MSPCs exhibit chromosomal abnormalities in up to 64% of MDS patients and up to 54% of AML patients, suggesting enhanced genetic instability of MSPCs in these diseases [ 597 , 600 , 601 ]. Alternatively, the earliest cells involved in leukemogenesis did not express any of these lesions, but did acquire them after diversification into hematopoietic and non-hematopoietic sub-clones.…”

Section: Mspcs In Mds and Aml: Clone-derived Or Clone-induced?mentioning

confidence: 99%

Mesenchymal Stem and Progenitor Cells in Normal and Dysplastic Hematopoiesis—Masters of Survival and Clonality?

Pleyer

Valent

Greil

2016

IJMS

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Myelodysplastic syndromes (MDS) are malignant hematopoietic stem cell disorders that have the capacity to progress to acute myeloid leukemia (AML). Accumulating evidence suggests that the altered bone marrow (BM) microenvironment in general, and in particular the components of the stem cell niche, including mesenchymal stem cells (MSCs) and their progeny, play a pivotal role in the evolution and propagation of MDS. We here present an overview of the role of MSCs in the pathogenesis of MDS, with emphasis on cellular interactions in the BM microenvironment and related stem cell niche concepts. MSCs have potent immunomodulatory capacities and communicate with diverse immune cells, but also interact with various other cellular components of the microenvironment as well as with normal and leukemic stem and progenitor cells. Moreover, compared to normal MSCs, MSCs in MDS and AML often exhibit altered gene expression profiles, an aberrant phenotype, and abnormal functional properties. These alterations supposedly contribute to the “reprogramming” of the stem cell niche into a disease-permissive microenvironment where an altered immune system, abnormal stem cell niche interactions, and an impaired growth control lead to disease progression. The current article also reviews molecular targets that play a role in such cellular interactions and possibilities to interfere with abnormal stem cell niche interactions by using specific targeted drugs.

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Section: Mspcs In Mds and Aml: Clone-derived Or Clone-induced?mentioning

confidence: 99%

Mesenchymal Stem and Progenitor Cells in Normal and Dysplastic Hematopoiesis—Masters of Survival and Clonality?

Pleyer

Valent

Greil

2016

IJMS

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“…Various cytogenetic abnormalities have been shown to be present in MSPCs of up to 50% of patients with MDS, which are different from those detectable in the HSPC compartment. 73 Chromosomes 1 and 7 were shown to be more frequently involved in MSPC structural aberrations and a correlation between aberrations in MSPCs and overall survival has been published. 74 The presence of chromosomal abnormalities (mainly aneuploidy) in MDS-MSPCs is associated with the deregulated expression of AURKA and AURKB genes.…”

Section: The Impact Of the Osteo-hematopoietic Niche On The Pathogenementioning

confidence: 99%

Myelodysplasia is in the niche: novel concepts and emerging therapies

et al. 2014

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Myelodysplastic syndromes (MDSs) represent clonal disorders mainly of the elderly that are characterized by ineffective hematopoiesis and an increased risk of transformation into acute myeloid leukemia. The pathogenesis of MDS is thought to evolve from accumulation and selection of specific genetic or epigenetic events. Emerging evidence indicates that MDS is not solely a hematopoietic disease but rather affects the entire bone marrow microenvironment, including bone metabolism. Many of these cells, in particular mesenchymal stem and progenitor cells (MSPCs) and osteoblasts, express a number of adhesion molecules and secreted factors that regulate blood regeneration throughout life by contributing to hematopoietic stem and progenitor cell (HSPC) maintenance, self-renewal and differentiation. Several endocrine factors, such as erythropoietin, parathyroid hormone and estrogens, as well as deranged iron metabolism modulate these processes. Thus, interactions between MSPC and HSPC contribute to the pathogenesis of MDS and associated pathologies. A detailed understanding of these mechanisms may help to define novel targets for diagnosis and possibly therapy. In this review, we will discuss the scientific rationale of ‘osteohematology' as an emerging research field in MDS and outline clinical implications.

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P-254 Chromosomal analysis of hematopoietic and stromal progenitor cells in patients with myelodysplastic syndrome (MDS)

Cited by 2 publications

References 0 publications

Mesenchymal Stem and Progenitor Cells in Normal and Dysplastic Hematopoiesis—Masters of Survival and Clonality?

Mesenchymal Stem and Progenitor Cells in Normal and Dysplastic Hematopoiesis—Masters of Survival and Clonality?

Myelodysplasia is in the niche: novel concepts and emerging therapies

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