T-ALL and thymocytes: a message of noncoding RNAs

Wallaert, Annelynn; Durinck, Kaat; Taghon, Tom; Vlierberghe, Pieter Van; Speleman, Franki

doi:10.1186/s13045-017-0432-0

Cited by 25 publications

(15 citation statements)

References 163 publications

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“…Medical advances have improved the survival of adult patients with acute lymphoblastic leukemia (ALL) over the past few decades. T cell acute lymphoblastic leukemia (T-ALL) is one of the most aggressive hematologic malignancies, accounting for up to 10–15% of pediatric ALL and 25% of adult ALL cases [ 1 ], and arises from the malignant transformation of T cell progenitors [ 2 , 3 ]. Although high-dose multi-agent chemotherapy is clinically effective in most cases, primary drug resistance and relapse are frequently observed [ 4 ], preventing T-ALL from being cured [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Cell adhesion-mediated mitochondria transfer contributes to mesenchymal stem cell-induced chemoresistance on T cell acute lymphoblastic leukemia cells

et al. 2018

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BackgroundDespite the high cure rate of T cell acute lymphoblastic leukemia (T-ALL), drug resistance to chemotherapy remains a significant clinical problem. Bone marrow mesenchymal stem cells (MSCs) protect leukemic cells from chemotherapy, but the underlying mechanisms are poorly understood. In this study, we aimed to uncover the mechanism of MSC-induced chemoresistance in T-ALL cells, thus providing a promising clinical therapy target.MethodsCell viability was determined using the viability assay kit CCK-8. The mitochondrial ROS levels were detected using the fluorescent probe MitoSOX™ Red, and fluorescence intensity was measured by flow cytometry. In vitro, MSCs and Jurkat cells were cocultured. MSCs were labeled with green fluorescent protein (GFP), and Jurkat cells were labeled with the mitochondria-specific dye MitoTracker Red. Bidirectional mitochondrial transfer was detected by flow cytometry and confocal microscopy. The mechanism of mitochondria transfer was analyzed by inhibitor assays. Transcripts related to Jurkat cell/MSC adhesion in the coculture system were assessed by qRT-PCR. After treatment with a neutralizing antibody against a key adhesion molecule, mitochondria transfer from Jurkat cells to MSCs was again detected by flow cytometry and confocal microscopy. Finally, we verified our findings using human primary T-ALL cells cocultured with MSCs.ResultsChemotherapeutic drugs caused intracellular oxidative stress in Jurkat cells. Jurkat cells transfer mitochondria to MSCs but receive few mitochondria from MSCs, resulting in chemoresistance. This process of mitochondria transfer is mediated by tunneling nanotubes, which are protrusions that extend from the cell membrane. Moreover, we found that most Jurkat cells adhered to MSCs in the coculture system, which was mediated by the adhesion molecule ICAM-1. Treatment with a neutralizing antibody against ICAM-1 led to a decreased number of adhering Jurkat cells, decreased mitochondria transfer, and increased chemotherapy-induced cell death.ConclusionsWe show evidence that mitochondria transfer from Jurkat cells to MSCs, which is mediated by cell adhesion, may be a potential therapeutic target for T-ALL treatment.Electronic supplementary materialThe online version of this article (10.1186/s13045-018-0554-z) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Cell adhesion-mediated mitochondria transfer contributes to mesenchymal stem cell-induced chemoresistance on T cell acute lymphoblastic leukemia cells

et al. 2018

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“…21 The profiles of these miRNAs could differ based on the tumor type and, hence, might provide novel biomarkers for diagnosis of many cancers. 22,23 It has been shown the expression levels of miR-181a, miR-128-3P and miR-142-3p were significantly up-regulated in T-ALL patients, 1,4,24 whereas miR-204, miR-101 and miR-193b-3p were down-regulated. 2,24,25 Some studies have indicated that FBXW7 dysregulates important signaling pathways including Notch1 and Notes: a Targeting of FBXW7 is confirmed by the software.…”

Section: Discussionmentioning

confidence: 99%

“…Notch1 signaling alteration is strongly related to T-ALL progression. 5,24 Since malfunction of FBXW7 has been reported in several types of human cancer, this protein seems as an appropriate choice for miRNA targeting studies. Therefore, the focus of the present study was to compare the expression levels of miR-32, miR-107, and FBXW7 using RT-qPCR in the plasma of patients with T-ALL.…”

Section: Discussionmentioning

confidence: 99%

<p>Alteration in Expression of miR-32 and FBXW7 Tumor Suppressor in Plasma Samples of Patients with T-cell Acute Lymphoblastic Leukemia</p>

Mansouri

Khansarinejad

Mosayebi

et al. 2020

CMAR

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Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and malignant neoplasm that arises from the hematopoietic T-cell precursors. Inactivation of FBXW7 gene is frequently observed in T-cell acute lymphoblastic leukemia, suggesting a significant tumor-suppressive role for FBXW7 in the pathobiology of this leukemia. Considering the role of microRNAs in cell proliferation and regulation of apoptosis, the aim of this study was to identify novel oncogenic microRNAs that suppress FBXW7 in patients with T-ALL. Patients and Methods: The expression levels of two bioinformatically predicted microRNAs -miR-32 and miR-107 were compared in patients with T-ALL and a control group. A total of 80 plasma samples were subjected to RNA extraction, and the microRNA expression profiles were assessed by the RT-qPCR. The expression level of miR-103 was used as the endogenous reference for normalization of quantitative data. Results: The plasma levels of miR-32 and miR-107 in patients with T-ALL were significantly higher (5.65, P < 0.001) and lower (0.432, P = 0.002), respectively. On the other hand, the expression levels of FBXW7 gene were significantly downregulated by -76.9 fold in T-ALL patients (P < 0.001). The results of the ROC curve analysis indicated that overexpression of miR-32 might be used to distinguish T-ALL patients with reasonable sensitivity and specificity. Conclusion: miR-32 is considered as a novel oncomir that targets FBXW7 and might have a role in the etiology or progression of T-ALL. Furthermore, miR-32 can potentially serve as a non-invasive biomarker for detection of T-ALL.

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“…For example, Wendel et al have shown that miR-19 from the miR-17 ~ 92 cluster is sufficient to promote leukemogenesis in Notch1-induced T-ALL [139]. Regarding lncRNAs, Wallaerts et al performed an expression profile in primary T-ALL cases, which was able to classify T-ALL subgroups based on their expression pattern [140]. Trimarchi et al have reported that LUNAR1 (leukemia-induced noncoding activator RNA1) was a NOTCH1 target that plays an oncogenic role by regulating IGF1R expression [141].…”

Section: Transcriptional Targets Of Tal1 In T-all Cells: Non-coding Rnasmentioning

confidence: 99%

Oncogenic transcriptional program driven by TAL1 in T-cell acute lymphoblastic leukemia

2018

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TAL1/SCL is a prime example of an oncogenic transcription factor that is abnormally expressed in acute leukemia due to the replacement of regulator elements. This gene has also been recognized as an essential regulator of hematopoiesis. TAL1 expression is strictly regulated in a lineage- and stage-specific manner. Such precise control is crucial for the switching of the transcriptional program. The misexpression of TAL1 in immature thymocytes leads to a widespread series of orchestrated downstream events that affect several different cellular machineries, resulting in a lethal consequence, namely T-cell acute lymphoblastic leukemia (T-ALL). In this article, we will discuss the transcriptional regulatory network and downstream target genes, including protein-coding genes and non-coding RNAs, controlled by TAL1 in normal hematopoiesis and T-cell leukemogenesis.

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T-ALL and thymocytes: a message of noncoding RNAs

Cited by 25 publications

References 163 publications

Cell adhesion-mediated mitochondria transfer contributes to mesenchymal stem cell-induced chemoresistance on T cell acute lymphoblastic leukemia cells

Cell adhesion-mediated mitochondria transfer contributes to mesenchymal stem cell-induced chemoresistance on T cell acute lymphoblastic leukemia cells

<p>Alteration in Expression of miR-32 and FBXW7 Tumor Suppressor in Plasma Samples of Patients with T-cell Acute Lymphoblastic Leukemia</p>

Oncogenic transcriptional program driven by TAL1 in T-cell acute lymphoblastic leukemia

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