Comparative Analysis of the Genetic Variants in Haematopoietic Stem/Progenitor and Mesenchymal Stem Cell Compartments in de novo Myelodysplastic Syndromes

Bandara, Wmms; Rathnayake, Anuruddhika; Neththikumara, Nilaksha; Goonasekera, H W W; Dissanayake, Vajira H W

doi:10.1016/j.bcmd.2021.102535

Cited by 3 publications

(2 citation statements)

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“…In myeloid malignancies KDM6A is frequently mutated, resulting in reduced expression or loss of function [ 121 , 122 , 123 , 124 , 125 ]. KDM6A deficient mice display a CMML/MDS-like phenotype that frequently transforms into AML ( Table 1 ) [ 53 , 54 , 55 ].…”

Section: Resultsmentioning

confidence: 99%

The Cross Marks the Spot: The Emerging Role of JmjC Domain-Containing Proteins in Myeloid Malignancies

2021

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Histone methylation tightly regulates chromatin accessibility, transcription, proliferation, and cell differentiation, and its perturbation contributes to oncogenic reprogramming of cells. In particular, many myeloid malignancies show evidence of epigenetic dysregulation. Jumonji C (JmjC) domain-containing proteins comprise a large and diverse group of histone demethylases (KDMs), which remove methyl groups from lysines in histone tails and other proteins. Cumulating evidence suggests an emerging role for these demethylases in myeloid malignancies, rendering them attractive targets for drug interventions. In this review, we summarize the known functions of Jumonji C (JmjC) domain-containing proteins in myeloid malignancies. We highlight challenges in understanding the context-dependent mechanisms of these proteins and explore potential future pharmacological targeting.

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Section: Resultsmentioning

confidence: 99%

The Cross Marks the Spot: The Emerging Role of JmjC Domain-Containing Proteins in Myeloid Malignancies

2021

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“…Those leukemic MSCs are aging, growth deficiency and osteogenic differentiation ( Geyh et al, 2013 ; Geyh et al, 2016 ). The function-related gene sets, such as TBX15, PITX2, HOXB6, are regulated by relevant specific hypermethylation signals ( Geyh et al, 2016 ; Bandara et al, 2021 ). At the same time, multiple studies have confirmed that multiple methylases strictly control the cell stemness, senescence ( Cakouros and Gronthos, 2020 ) and differentiation functions ( Ye et al, 2012 ) of MSCs ( Sui et al, 2020 ), and the loss of KDM4B mimics a leukemia-like MSCs( Deng et al, 2021 ), suggesting that leukemia cells epigenetic change MSCs for its BMM remodeling.…”

Section: Lscs Facilitate Transformation Of Mscs Into Lsc-beneficial N...mentioning

confidence: 99%

Regulation of Malignant Myeloid Leukemia by Mesenchymal Stem Cells

Tan

Chen

Wong

et al. 2022

Front. Cell Dev. Biol.

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Bone marrow microenvironment (BMM) has been proven to have benefits for both normal hematopoietic stem cell niche and pathological leukemic stem cell niche. In fact, the pathological leukemia microenvironment reprograms bone marrow niche cells, especially mesenchymal stem cells for leukemia progression, chemoresistance and relapse. The growth and differentiation of MSCs are modulated by leukemia stem cells. Moreover, chromatin abnormality of mesenchymal stem cells is sufficient for leukemia initiation. Here, we summarize the detailed relationship between MSC and leukemia. MSCs can actively and passively regulate the progression of myelogenous leukemia through cell-to-cell contact, cytokine-receptor interaction, and exosome communication. These behaviors benefit LSCs proliferation and survival and inhibit physiological hematopoiesis. Finally, we describe the recent advances in therapy targeting MSC hoping to provide new perspectives and therapeutic strategies for leukemia.

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