5-Azacytidine restores interleukin 6-increased production in mesenchymal stromal cells from myelodysplastic patients

Boada, Matilde; Echarte, L.; Guillermo, Cecilia; Díaz, Lilián; Touriño, Cristina; Grille, Sofía

doi:10.1016/j.htct.2019.12.002

Cited by 17 publications

(8 citation statements)

References 28 publications

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“…Engineered human placenta-derived MSCs, armed with a double fusion gene containing the herpes simplex virus truncated thymidine kinase and firefly luciferase, inhibited the tumorigenesis mediated by the HT29 colon cancer cell line in nude mice 114 . Treatment with 5-azacytidine restored IL-6-increased production in MSCs from myelodysplastic patients 116 .…”

Section: Stromal Cells Follow the Program Dictated By Their Microenvimentioning

confidence: 93%

Emerging data supporting stromal cell therapeutic potential in cancer: reprogramming stromal cells of the tumor microenvironment for anti-cancer effects

et al. 2020

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Section: Stromal Cells Follow the Program Dictated By Their Microenvimentioning

confidence: 93%

Emerging data supporting stromal cell therapeutic potential in cancer: reprogramming stromal cells of the tumor microenvironment for anti-cancer effects

et al. 2020

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“…Gene-humanizations via knock-in significantly improve the engraftment, differentiation and maintenance of human cells from MDS and other hematologic malignancies. [25][26][27] As MDS is an inflammatory disorder with elevated IL-6 levels and is highly dependent on its microenvironment, 28,29 we made use of a next-generation version of MISTRG with humanization via targeted insertion of human interleukin-6 (IL-6), in short, 'MISTRG6'. MISTRG6 have been shown recently to efficiently engraft healthy human huCD34 + and myeloma cells.…”

Section: Combined Mcl1 and Bcl2 Inhibition Reduces Human Mds Cell Eng...mentioning

confidence: 99%

Selective inhibition of MCL1 overcomes venetoclax resistance in a murine model of myelodysplastic syndromes

Fischer

Song

Arrate³

et al. 2022

haematol

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Treatment for myelodysplastic syndromes (MDS) remains insufficient due to clonal heterogeneity and lack of effective clinical therapies. Dysregulation of apoptosis is observed across MDS subtypes regardless of mutations and represents an attractive therapeutic opportunity. Venetoclax (VEN), a selective inhibitor of anti-apoptotic protein B-cell lymphoma-2 (BCL2), has yielded impressive responses in older patients with acute myeloid leukemia (AML) and high risk MDS. BCL2 family anti-apoptotic proteins BCL-XL and induced myeloid cell leukemia 1 (MCL1) are implicated in leukemia survival, and upregulation of MCL1 is seen in VEN-resistant AML and MDS. We determined in vitro sensitivity of MDS patient samples to selective inhibitors of BCL2, BCL-XL and MCL1. While VEN response positively correlated with MDS with excess blasts, all MDS subtypes responded to MCL1 inhibition. Treatment with combined VEN+MCL1 inhibtion was synergistic in all MDS subtypes without significant injury to normal hematopoiesis and reduced MDS engraftment in MISTRG6 mice, supporting the pursuit of clinical trials with combined BCL2+MCL1 inhibition in MDS.

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“…Hypometilating agents have shown to regulate adaptive immunity and cytokine secretome in MDSs, both in vivo and in vitro. Azacytidine (AZA) reduces IL-6 production in MDS–MSCs, thus contributing to the recovery of normal hematopoiesis [ 119 ] and also through the regulation of extracellular matrix [ 120 ]. In addition, the demethylating activity of AZA is also extended to MSCs: AZA treatment induces demethylation and thus increases the expression of SPINT2/HAI-2, which is methylated and silenced in MDSss and AML [ 121 ].…”

Section: The Role Of Mesenchymal Stem Cells In Myelodysplastic Synmentioning

confidence: 99%

Mesenchymal Stem Cells in Aplastic Anemia and Myelodysplastic Syndromes: The “Seed and Soil” Crosstalk

Fattizzo

Giannotta

Barcellini

2020

IJMS

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There is growing interest in the contribution of the marrow niche to the pathogenesis of bone marrow failure syndromes, i.e., aplastic anemia (AA) and myelodysplastic syndromes (MDSs). In particular, mesenchymal stem cells (MSCs) are multipotent cells that contribute to the organization and function of the hematopoietic niche through their repopulating and supporting abilities, as well as immunomodulatory properties. The latter are of great interest in MDSs and, particularly, AA, where an immune attack against hematopoietic stem cells is the key pathogenic player. We, therefore, conducted Medline research, including all available evidence from the last 10 years concerning the role of MSCs in these two diseases. The data presented show that MSCs display morphologic, functional, and genetic alterations in AA and MDSs and contribute to immune imbalance, ineffective hematopoiesis, and leukemic evolution. Importantly, adoptive MSC infusion from healthy donors can be exploited to heal the “sick” niche, with even better outcomes if cotransplanted with allogeneic hematopoietic stem cells. Finally, future studies on MSCs and the whole microenvironment will further elucidate AA and MDS pathogenesis and possibly improve treatment.

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5-Azacytidine restores interleukin 6-increased production in mesenchymal stromal cells from myelodysplastic patients

Cited by 17 publications

References 28 publications

Emerging data supporting stromal cell therapeutic potential in cancer: reprogramming stromal cells of the tumor microenvironment for anti-cancer effects

Emerging data supporting stromal cell therapeutic potential in cancer: reprogramming stromal cells of the tumor microenvironment for anti-cancer effects

Selective inhibition of MCL1 overcomes venetoclax resistance in a murine model of myelodysplastic syndromes

Mesenchymal Stem Cells in Aplastic Anemia and Myelodysplastic Syndromes: The “Seed and Soil” Crosstalk

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