Regulation of the miRNA expression by TEL/AML1, BCR/ABL, MLL/AF4 and TCF3/PBX1 oncoproteins in acute lymphoblastic leukemia (Review)

Organista‐Nava, Jorge; Gómez‐Gómez, Yazmín; Illades‐Aguiar, Berenice; Leyva‐Vázquez, Marco Antonio

doi:10.3892/or.2016.4948

Cited by 16 publications

(12 citation statements)

References 58 publications

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“…26 Common fusion genes in ALL patients include the BCR/ABL fusion gene and the TEL/AML1 (ETV6 /RUNX1) fusion gene with an incidence of ~6%-35%, and the latter is considered to be a fusion genes associated with good prognosis. 27 Herein, we also found that the expression of PKM2 in ALL patients with BCR/ABL gene fusion was higher than that in other patients without gene fusion, while there was no statistically significant difference in the expression level of PKM2 between AML patients with PML-RARA gene fusion or ALL patients with TEL/AML1 gene fusion. Studies have confirmed that BCR-ABL fusion gene encodes BCR-ABL fusion protein and drives tumor transformation of hematopoietic stem cells, which can stimulate the PI3K/Akt/ mTOR signal transduction and lead to impaired autophagy of leukemia cells.…”

supporting

confidence: 48%

High Expression of PKM2 Was Associated with the Poor Prognosis of Acute Leukemia

Huang

Chen

Xie

et al. 2021

CMAR

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Purpose: To explore the clinical significance of plasma pyruvate kinase M2 (PKM2) in assessing the incidence and prognosis of acute leukemia. Methods: Plasma samples from 56 acute myeloid leukemia (AML) patients, 40 acute lymphoblastic leukemia (ALL) patients, and 66 plasma samples from healthy individuals were collected. The level of plasma PKM2 was detected by enzyme-linked immunosorbent assay. The clinical significance of PKM2 in acute leukemia was assessed by analyzing receiver operating characteristic and survival curves. Results:The plasma levels of PKM2 in AML or ALL patients were significantly higher than those in healthy individuals, respectively. PKM2 can be used as a potential diagnostic index with the AUC of 0.827 for AML and 0.837 for ALL. The level of plasma PKM2 in ALL patients with a BCR/ABL-positive genotype was significantly higher than that in patients with a BCR/ABL-negative genotype (p<0.05). The event-free survival and the overall survival of acute leukemia patients with higher PKM2 expression was worse than those with lower PKM2 expression. Conclusion: This study showed that higher levels of PKM2 was negatively correlated with the prognosis of acute leukemia. Therefore, PKM2 can be used as a potential index to assess the incidence and prognosis of acute leukemia.

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confidence: 48%

High Expression of PKM2 Was Associated with the Poor Prognosis of Acute Leukemia

Huang

Chen

Xie

et al. 2021

CMAR

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“…15 MiRNAs may be especially important in regulating the expression of TFs such as MYB that has distinct biological effects in normal hematopoiesis and in leukemic cells based on its expression levels. 15,16 Regulation of MYB expression through miRNAs has been reported previously. 17–20 Levels of MYB expression may be differentially controlled by multiple miRNAs and, conversely, MYB could control the expression of different miRNAs 9,17–21 to execute lineage-specific developmental choices at critical junctions during hematopoiesis.…”

Section: Introductionmentioning

confidence: 79%

“…47 On the other hand, silencing MYB alone does not abolish expression of the miR-17-92 cluster, suggesting that other transcription factors also regulate the expression of the miR-17-92 cluster in BCR-ABL1 -transformed cells. 16 Compared to control cells, MYB -silenced BV173 cells exhibit a marked inhibition of cell growth which is due to cell-cycle arrest and induction of apoptosis. 48 Thus, we asked whether restoring expression of the miR-17-92 cluster would rescue the impaired growth of MYB -silenced BV173 cells.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional activation of the miR-17-92 cluster is involved in the growth-promoting effects of MYB in human Ph-positive leukemia cells

Spagnuolo¹,

Regazzo²,

Dominici

et al. 2018

Haematologica

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MicroRNAs, non-coding regulators of gene expression, are likely to function as important downstream effectors of many transcription factors including MYB. Optimal levels of MYB are required for transformation/maintenance of BCR-ABL1-expressing cells. We investigated whether MYB silencing modulates microRNAs expression in Philadelphia-positive leukemia cells and if MYB-regulated microRNAs are important for the MYB addiction of these cells. 35 microRNAs were modulated by MYB silencing in chronic lymphoid and erythro-myeloid blast crisis BV173 and K562 leukemia cells; 15 of these were concordantly modulated in both lines. We focused on the miR-17-92 cluster because of its oncogenic role in tumors and found that: i) it is a direct MYB target; ii) it partially rescued the impaired proliferation and enhanced apoptosis of MYB-silenced BV173 cells. Moreover, we identified FRZB, a Wnt/β-catenin pathway inhibitor, as a novel target of the miR-17-92 cluster. High expression of MYB in blast cells from two Ph-positive leukemia patients correlated positively with the miR-17-92 cluster and inversely with FRZB. This expression pattern was also observed in a microarray dataset of 122 Ph-positive acute lymphoblastic leukemias. In vivo experiments in NOD scid gamma mice injected with BV173 cells confirmed that FRZB functions as a Wnt/β-catenin inhibitor even as they failed to demonstrate that this pathway is important for BV173-dependent leukemogenesis. These studies illustrate the global effects of MYB expression on the microRNAs profile of Ph-positive cells and supports the concept that the MYB addiction of these cells is, in part, caused by modulation of microRNA-regulated pathways affecting cell proliferation and survival.

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“…Finally, miR-708 upregulation was associated with a good prognosis, as lower relapse risk, low WBC count, and better overall survival were detected in ALL cases; on the contrary, miR-708 downregulation was revealed in poor prognosis subtypes as T-ALL and cases with MLL gene rearrangement [122,139]. Finally, in ALL with TCF3-PBX1 fusion, the deregulation of several miRNAs was also revealed (Table 1) [123,127].…”

Section: Acute Lymphoblastic Leukemiamentioning

confidence: 98%

Dysregulation of miRNA in Leukemia: Exploiting miRNA Expression Profiles as Biomarkers

Anelli

Zagaria

Specchia

et al. 2021

IJMS

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Micro RNAs (miRNAs) are a class of small non-coding RNAs that have a crucial role in cellular processes such as differentiation, proliferation, migration, and apoptosis. miRNAs may act as oncogenes or tumor suppressors; therefore, they prevent or promote tumorigenesis, and abnormal expression has been reported in many malignancies. The role of miRNA in leukemia pathogenesis is still emerging, but several studies have suggested using miRNA expression profiles as biomarkers for diagnosis, prognosis, and response to therapy in leukemia. In this review, the role of miRNAs most frequently involved in leukemia pathogenesis is discussed, focusing on the class of circulating miRNAs, consisting of cell-free RNA molecules detected in several body fluids. Circulating miRNAs could represent new potential non-invasive diagnostic and prognostic biomarkers of leukemia that are easy to isolate and characterize. The dysregulation of some miRNAs involved in both myeloid and lymphoid leukemia, such as miR-155, miR-29, let-7, and miR-15a/miR-16-1 clusters is discussed, showing their possible employment as therapeutic targets.

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Regulation of the miRNA expression by TEL/AML1, BCR/ABL, MLL/AF4 and TCF3/PBX1 oncoproteins in acute lymphoblastic leukemia (Review)

Cited by 16 publications

References 58 publications

High Expression of PKM2 Was Associated with the Poor Prognosis of Acute Leukemia

High Expression of PKM2 Was Associated with the Poor Prognosis of Acute Leukemia

Transcriptional activation of the miR-17-92 cluster is involved in the growth-promoting effects of MYB in human Ph-positive leukemia cells

Dysregulation of miRNA in Leukemia: Exploiting miRNA Expression Profiles as Biomarkers

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