ADAMTS14, ARHGAP22, and EPDR1 as potential novel targets in acute myeloid leukaemia

El‐Masry, Omar S.; Alamri, Ali; Alzahrani, Faisal; Alsamman, Khaldoon

doi:10.1016/j.heliyon.2022.e09065

Cited by 2 publications

(2 citation statements)

References 26 publications

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“…These 2 candidates have been reported as promising therapeutic targets in cancer. 22 , 23 ARHGAP22 is implicated in tumor cell motility and plays a role in the survival-mediated effects of Akt signaling. 24 In addition, PARD6A has been identified as an inducer of cell migration and invasion, contributing to the metastasis of ovarian cancer.…”

Section: Resultsmentioning

confidence: 99%

Charting epimutation dynamics in human hematopoietic differentiation

Qin,

Lu,

et al. 2024

Blood Science

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DNA methylation plays a critical role in hematopoietic differentiation. Epimutation is a stochastic variation in DNA methylation that induces epigenetic heterogeneity. However, the effects of epimutations on normal hematopoiesis and hematopoietic diseases remain unclear. In this study, we developed a Julia package called EpiMut that enabled rapid and accurate quantification of epimutations. EpiMut was used to evaluate and provide an epimutation landscape in steady-state hematopoietic differentiation involving 13 types of blood cells ranging from hematopoietic stem/progenitor cells to mature cells. We showed that substantial genomic regions exhibited epigenetic variations rather than significant differences in DNA methylation levels between the myeloid and lymphoid lineages. Stepwise dynamics of epimutations were observed during the differentiation of each lineage. Importantly, we found that epimutation significantly enriched signals associated with lineage differentiation. Furthermore, epimutations in hematopoietic stem cells (HSCs) derived from various sources and acute myeloid leukemia were related to the function of HSCs and malignant cell disorders. Taken together, our study comprehensively documented an epimutation map and uncovered its important roles in human hematopoiesis, thereby offering insights into hematopoietic regulation.

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Section: Resultsmentioning

confidence: 99%

Charting epimutation dynamics in human hematopoietic differentiation

Qin,

Lu,

et al. 2024

Blood Science

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“…Our RNA sequencing results suggest that exogenous high steroidal treatment of adrenocortical cells, especially with 17OHP, activates genes involved in cell proliferation and progression. ADAMTS14 protein, a metallopeptidase that degrades the extracellular matrix and its components, and thus increases cell migration and invasion, was found to be expressed in the tumor cells [ 49 , 50 ]. Increased expression of ADAMTS14 in our study signifies the role of steroids in cell invasion.…”

Section: Discussionmentioning

confidence: 99%

Evidence of the Role of Inflammation and the Hormonal Environment in the Pathogenesis of Adrenal Myelolipomas in Congenital Adrenal Hyperplasia

Kolli,

Frucci,

da Cunha

et al. 2024

IJMS

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Adrenal myelolipomas (AML) are composed of mature adipose and hematopoietic components. They represent approximately 3 percent of adrenal tumors and are commonly found in patients with congenital adrenal hyperplasia (CAH). CAH provides a unique environment to explore AML pathogenesis. We aimed to evaluate the role of the immune system and hormones that accumulate in poorly controlled CAH in the development of AML. When compared to normal adrenal tissue, CAH-affected adrenal tissue and myelolipomas showed an increased expression of inflammatory cells (CD68, IL2Rbeta), stem cells (CD117) B cells (IRF4), and adipogenic markers (aP2/FABP4, AdipoQ, PPARγ, Leptin, CideA), and immunostaining showed nodular lymphocytic accumulation. Immunohistochemistry staining revealed a higher density of inflammatory cells (CD20, CD3, CD68) in CAH compared to non-CAH myelolipomas. In vitro RNA-sequencing studies using NCI-H295R adrenocortical cells with exogenous exposure to ACTH, testosterone, and 17-hydroxyprogesterone hormones, showed the differential expression of genes involved in cell cycle progression, phosphorylation, and tumorigenesis. Migration of B-lymphocytes was initiated after the hormonal treatment of adrenocortical cells using the Boyden chamber chemotaxis assay, indicating a possible hormonal influence on triggering inflammation and the development of myelolipomas. These findings demonstrate the important role of inflammation and the hormonal milieu in the development of AML in CAH.

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ADAMTS14, ARHGAP22, and EPDR1 as potential novel targets in acute myeloid leukaemia

Cited by 2 publications

References 26 publications

Charting epimutation dynamics in human hematopoietic differentiation

Charting epimutation dynamics in human hematopoietic differentiation

Evidence of the Role of Inflammation and the Hormonal Environment in the Pathogenesis of Adrenal Myelolipomas in Congenital Adrenal Hyperplasia

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