Notch affects the prodifferentiating effect of retinoic acid and <scp>PMA</scp> on leukemic cells

Matulić, Maja; Skelin, Josipa; Radić-Krišto, Delfa; Kardum-Skelin, Ika; Grčević, Danka; Antica, Mariastefania

doi:10.1002/cyto.a.22582

Cited by 5 publications

(5 citation statements)

References 26 publications

(34 reference statements)

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“…In the OE, HBC activation and that transition are restrained by Notch signaling, which drives p63 expression in vivo (Herrick et al., 2017); HES1 expression by HBCs in culture prior to differentiation, are high, consistent with a similar role. Several reports indicate that RA and Notch signaling have an antagonistic relationship (Matulic et al., 2015, Mezquita et al., 2014, Ryu et al., 2015).…”

Section: Discussionmentioning

confidence: 99%

Activating a Reserve Neural Stem Cell Population In Vitro Enables Engraftment and Multipotency after Transplantation

et al. 2019

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Summary The olfactory epithelium (OE) regenerates after injury via two types of tissue stem cells: active globose cells (GBCs) and dormant horizontal basal cells (HBCs). HBCs are roused to activated status by OE injury when P63 levels fall. However, an in-depth understanding of activation requires a system for culturing them that maintains both their self-renewal and multipotency while preventing spontaneous differentiation. Here, we demonstrate that mouse, rat, and human HBCs can be cultured and passaged as P63+ multipotent cells. HBCs in vitro closely resemble HBCs in vivo based on immunocytochemical and transcriptomic comparisons. Genetic lineage analysis demonstrates that HBCs in culture arise from both tissue-derived HBCs and multipotent GBCs. Treatment with retinoic acid induces neuronal and non-neuronal differentiation and primes cultured HBCs for transplantation into the lesioned OE. Engrafted HBCs generate all OE cell types, including olfactory sensory neurons, confirming that HBC multipotency and neurocompetency are maintained in culture.

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Section: Discussionmentioning

confidence: 99%

Activating a Reserve Neural Stem Cell Population In Vitro Enables Engraftment and Multipotency after Transplantation

et al. 2019

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“…Cells were washed in PBS (supplemented with 2% FCS), labeled with primary antibodies for 20 min, washed, and, when appropriate, labeled with a secondary anti-mouse IgG2b Alexa Fluor647 antibody (Invitrogen, Carlsbad, CA, USA) for 20 min. Antibodies to CD5 (TONBO), CD19 (TONBO and eBioscience), BCL-2 (BD), HES1 (Abnova), and NOTCH1 (LSBio) were used [ 27 , 28 ]. Each experiment also included isotype controls.…”

Section: Methodsmentioning

confidence: 99%

“…The lymphocytes of patients with a population of ≥95% CD5 + CD19 + cells, and reflecting the composition of the study population by sex and Binet and Rai classification, were selected and processed as previously described [ 9 , 28 ]. Briefly, 5 µg of proteins from each sample were separated using SDS-PAGE on a 10% gel, transferred to a nitrocellulose membrane, blocked in Blotto buffer for one hour, and incubated overnight with primary antibodies: Rabbit anti-human AIOLOS, Rabbit anti-human cleaved NOTCH1, Rabbit anti-human NOTCH1, and Rabbit anti-human β-ACTIN (all from Cell Signaling Technology, Inc., Beverly, MA, USA) [ 27 , 28 ]. After washing, the horseradish peroxidase (HRP)-linked anti-rabbit antibody was applied for one hour and the signal was detected by chemiluminescence using Supersignal West Pico plus (Thermo Fisher Scientific, Waltham, MA, USA) on a UVITEC Imaging System (Cleaver Scientific, Rugby, UK).…”

Section: Methodsmentioning

confidence: 99%

Analysis of Primary Chronic Lymphocytic Leukemia Cells’ Signaling Pathways

Skelin,

Matulić,

Milković

et al. 2024

Biomedicines

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Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder characterized by a specific expansion of mature B-cell clones. We hypothesized that the disease has a heterogeneous clinical outcome that depends on the genes and signaling pathways active in the malignant clone of the individual patient. It was found that several signaling pathways are active in CLL, namely, NOTCH1, the Ikaros family genes, BCL2, and NF-κB, all of which contribute to cell survival and the proliferation of the leukemic clone. Therefore, we analyzed primary CLL cells for the gene and protein expression of NOTCH1, DELTEX1, HES1, and AIOLOS in both peripheral blood lymphocytes (PBLs) and the bone marrow (BM) of patients, as well as the expression of BCL2 and miRNAs to see if they correlate with any of these genes. BCL2 and AIOLOS were highly expressed in all CLL samples as previously described, but we show here for the first time that AIOLOS expression was higher in the PBLs than in the BM. On the other hand, NOTCH1 activation was higher in the BM. In addition, miR-15a, miR-181, and miR-146 were decreased and miR-155 had increased expression in most samples. The activation of the NOTCH pathway in vitro increases the susceptibility of primary CLL cells to apoptosis despite high BCL2 expression.

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“…Alternatively, the inhibition of the Notch pathway increases the differentiation of fibroblasts to cardiomyocytes through Mef-2 expression (Abad et al, 2017). In addition, as it has been shown that the expression of Notch pathway in APL patients prevents the differentiation of promyelocytes by all-trans retinoic acid (Matulic et al, 2015), it can be said that inhibiting the expression of Notch in APL not only reduces the number of promyelocytes due to their differentiation but can reduce the cardiotoxicity of ATO by inducing the differentiation of cardiomyocytes. Identifying the pathways that lead to Mef-2-induced differentiation of cardiomyocytes can provide a new approach to regenerative medicine to prevent cardiotoxicity associated with ATO use.…”

Section: Disruption Of Intracellular Calcium Homeostasismentioning

confidence: 99%

Strategies to inhibit arsenic trioxide‐induced cardiotoxicity in acute promyelocytic leukemia

Haybar

Shahrabi

Rezaeeyan

et al. 2019

Journal Cellular Physiology

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Objective Arsenic trioxide (ATO) is a drug commonly used for the treatment of acute promyelocytic leukemia (APL). Although ATO has been shown to cause significant improvement in patients, it is associated with serious side effects, which sometimes lead to the patient's death. In this review paper, we examine the reports of ATO‐induced cardiotoxicity in APL patients and evaluate the strategies to reduce the incidence of such toxicity. Methods The key search terms were “arsenic trioxide,” “acute promyelocytic leukemia,” “cardiotoxicity,” “molecular pathway,” and “biomarker.” Results Studies have indicated the involvement of several molecular pathways in ATO‐induced cardiotoxicity. These pathways increase the production of reactive oxygen species by interfering with intracellular calcium homeostasis as well as impairing the transfer of calcium into endoplasmic reticulum and mitochondria. On the other hand, increasing or decreasing expressions of some microRNAs (miRs) have been shown to play a role in cardiotoxicity. Conclusion Finally, it can be stated that given the essential role of molecular pathways in cardiotoxicity and considering the fact these pathways impair the regulation of miRs expression, identification of molecular pathways involved in ATO‐induced cardiotoxicity aimed at targeting miRs could be a new therapeutic strategy to prevent cardiotoxicity.

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Notch affects the prodifferentiating effect of retinoic acid and PMA on leukemic cells

Abstract: Notch proteins determine cell fate decisions in the development of diverse tissues.

Cited by 5 publications

References 26 publications

Activating a Reserve Neural Stem Cell Population In Vitro Enables Engraftment and Multipotency after Transplantation

Activating a Reserve Neural Stem Cell Population In Vitro Enables Engraftment and Multipotency after Transplantation

Analysis of Primary Chronic Lymphocytic Leukemia Cells’ Signaling Pathways

Strategies to inhibit arsenic trioxide‐induced cardiotoxicity in acute promyelocytic leukemia

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