Oncorequisite role of an aldehyde dehydrogenase in the pathogenesis of T-cell acute lymphoblastic leukemia

Zhang, Chujing; Amanda, Stella; Wang, Cheng; Tan, Tze King; Ali, Muhammad Zulfaqar; Leong, Wei Zhong; Ng, Ley Moy; Kitajima, Shojiro; Li, Zhenhua; Yeoh, Allen Eng Juh; Tan, Shi Hao; Sanda, Takaomi

doi:10.3324/haematol.2019.245639

Cited by 7 publications

(4 citation statements)

References 56 publications

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“…Overexpression of FGFR1, ALDH1A1 (ALDH1), EGFR, JAK2, histone deacetylases, and retinoic acid receptors has been frequently observed in SFT (44). In our data, we found significant overexpression of ALDH1 isoform ALDH1A2 in tumor tissue, a gene that can be overexpressed in T-cell acute lymphoblastic leukemias (45). In addition, it has been demonstrated that SFT has the potential to produce big IGF2 and cause hypoglycemia.…”

Section: Discussionsupporting

confidence: 60%

Solitary fibrous tumor with IGF-II-induced non-islet cell tumor hypoglycemia: a case report and molecular characterization by next-generation sequencing

Niedra,

Konrade,

Peculis

et al. 2023

Front. Oncol.

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BackgroundNon-islet cell tumor-induced hypoglycemia (NICTH) is a rare, life-threatening medical condition caused by excessive insulin-like growth factor II (IGF-II) secretion from tumors of most commonly mesenchymal origin. Using next-generation sequencing, we have characterized the genome and transcriptome of the resected IGF-II-secreting solitary fibrous tumor from a patient with severe hypoglycemia accompanied by hypoglycemia unawareness.Case presentationA 69-year-old male patient presenting with abdominal discomfort was examined using computer tomography, revealing a large lesion at the lesser pelvis extending above the umbilicus. As no bone and lymph node metastases were detected, the patient was scheduled for laparotomy. Before surgery, the patient presented with symptoms of severe hypoglycemia. Suppressed C-peptide levels and subsequent hypokalemia indicated a possible case of NICTH. The patient was treated with methylprednisolone (8 mg) to assess hypoglycemia. After the surgery, mild hypoglycemia was present for the postoperative period, and no radiological recurrences were observed 3 and 12 months after discharge. Histopathological examination results were consistent with the diagnosis of malignant solitary fibrous tumor (SFT). Overexpression of IGF-II was confirmed by both immunohistochemistry and RNA sequencing. Further NGS analysis revealed an SFT characteristic alteration—NAB2-STAT6 fusion. Additionally, three deleterious missense variants were detected in oncogenes BIRC6, KIT, and POLQ, and one homozygous in-frame deletion in the RBM10 tumor suppressor gene.ConclusionWhile the NAB2-STAT6 fusions are well characterized, the mutational landscape of SFTs remains understudied. This study reports the importance of NGS to characterize SFTs as we detected four coding variants in genes (BIRC6, KIT, POLQ, and RBM10) associated with tumorigenesis that could potentially contribute to the overall pathogenesis of SFT.

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Section: Discussionsupporting

confidence: 60%

Solitary fibrous tumor with IGF-II-induced non-islet cell tumor hypoglycemia: a case report and molecular characterization by next-generation sequencing

Niedra,

Konrade,

Peculis

et al. 2023

Front. Oncol.

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“…From this analysis, we observed changes in gene expression for several known TAL1 targets. For instance, ALDH1A2 , NKX3-1 , miR-223 , ARID5B and GIMAP family genes, which had been demonstrated to be directly regulated by TAL1, 10 , 16 , 24-26 were significantly downregulated at multiple time points, confirming that FKBP12 F36V -tagged TAL1 protein retains original function. Importantly, we found two distinct patterns of gene expression changes among the downregulated gene pool, termed “group A” and “group B” genes (Figure 1C-E).…”

Section: Resultsmentioning

confidence: 82%

“… 8 , 9 Thus, one of the main oncogenic mechanisms of TAL1 involves the induction of differentiation arrest. On the other hand, TAL1 can also induce a unique set of genes in human T-ALL, such as ALDH1A2 , 10 which has not been observed in mouse models. Notably, in many human T-ALL cases, the expression of TAL1 is driven by genetic mutations in an enhancer that can be activated by TAL1 and its regulatory partners (GATA3 and RUNX1) via an autoregulatory loop, forming the core regulatory circuit (CRC).…”

Section: Introductionmentioning

confidence: 96%

Regulatory mechanisms and context-dependent roles of TAL1 in T-cell acute lymphoblastic leukemia

Ong,

Tan,

Wang

et al. 2023

haematol

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T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy derived from thymic T-cell precursors. Approximately 40-60% of T-ALL cases exhibit aberrant overexpression of the TAL1 oncogenic transcription factor. Here, we provide a comprehensive view of the TAL1-induced transcriptional program in human T-ALL cells using a rapid protein degradation system coupled with integrative approaches. Our study demonstrates that TAL1 targets can be classified into several groups, each of which exhibits unique gene expression kinetics, chromatin features, and regulatory mechanisms. Group A genes are highly dependent on TAL1, many of which are not expressed in normal T-cells or TAL1-negative T-ALL cells, representing an oncogenic TAL1 signature. The TAL1 complex predominantly activates Group A genes. TAL1’s effect is not replaceable with its regulatory partners GATA3 or RUNX1. In contrast, Group B genes, many of which are generally expressed across different T-ALL subgroups, exhibit densely-connected chromatinchromatin interactions and demonstrate the collaborative roles played by TAL1 with other transcription factors. Interestingly, TAL1 cooperates with NOTCH1 to regulate gene expression in TAL1-positive T-ALL cells, whereas it potentially antagonizes the NOTCH1-MYC pathway and leads to lethality in TAL1-negative/TLX3-positive cells, demonstrating the context-dependent roles of TAL1.

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“…The gene was up-regulated in the compatible while down-regulated in the recalcitrant genotype at 6 hpi. Aldehyde dehydrogenase was showed that supported glycolysis and TCA cycle in mammalian cells [ 26 ]. The upregulated of Aldehyde dehydrogenase may promoted the production of metabolites in MDEC, and enhanced the growth of Agrobacterium .…”

Section: Discussionmentioning

confidence: 99%

Comparative transcriptome analysis reveals compatible and recalcitrant genotypic response of barley microspore-derived embryogenic callus toward Agrobacterium infection

Guo

et al. 2021

BMC Plant Biol

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Background The Agrobacterium mediated transformation has been routinely used in lots of plant species as a powerful tool to deliver genes of interest into a host plant. However, the transformation of elite and commercially valuable cultivar is still limited by the genotype-dependency, and the efficiency of Agrobacterium infection efficiency is crucial for the success of transformation. Results In this study, the microspore-derived embryogenic calli (MDEC) of barley elite cultivars and breeding lines were employed as unique subjects to characterize the genotypic response during Agrobacterium infection process. Our results identified compatible barley genotypes (GanPi 6 and L07, assigned as GP6-L07 group) and one recalcitrant genotype (Hong 99, assigned as H99) for the Agrobacterium strain LBA4404 infection using GUS assay. The accumulation trend of reactive oxygen species (ROS) was similar among genotypes across the time course. The results of RNA-seq depicted that the average expressional intensity of whole genomic genes was similar among barley genotypes during Agrobacterium infection. However, the numbers of differentially expressed genes (DEGs) exhibited significant expressional variation between GP6-L07 and H99 groups from 6 to 12 h post-inoculation (hpi). Gene ontology (GO) enrichment analysis revealed different regulation patterns for the predicted biological processes between the early (up-regulated DEGs overrepresented at 2 hpi) and late stages (down-regulated DEGs overrepresented from 6 to 24 hpi) of infection. KEGG analysis predicted 12 pathways during Agrobacterium infection. Among which one pathway related to pyruvate metabolism was enriched in GP6 and L07 at 6 hpi. Two pathways related to plant hormone signal transduction and DNA replication showed expressional variation between GP6-L07 and H99 at 24 hpi. It was further validated by qRT-PCR assay for seven candidate genes (Aldehyde dehydrogenase, SAUR, SAUR50, ARG7, Replication protein A, DNA helicase and DNA replication licensing factor) involved in the three pathways, which are all up-regulated in compatible while down-regulated in recalcitrant genotypes, suggesting the potential compatibility achieved at later stage for the growth of Agrobacterium infected cells. Conclusions Our findings demonstrated the similarity and difference between compatible and recalcitrant genotypes of barley MDEC upon Agrobacterium infection. Seven candidate genes involved in pyruvate metabolism, hormonal signal transduction and DNA replication were identified, which advocates the genotypic dependency during Agrobacterium infection process.

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Oncorequisite role of an aldehyde dehydrogenase in the pathogenesis of T-cell acute lymphoblastic leukemia

Cited by 7 publications

References 56 publications

Solitary fibrous tumor with IGF-II-induced non-islet cell tumor hypoglycemia: a case report and molecular characterization by next-generation sequencing

Solitary fibrous tumor with IGF-II-induced non-islet cell tumor hypoglycemia: a case report and molecular characterization by next-generation sequencing

Regulatory mechanisms and context-dependent roles of TAL1 in T-cell acute lymphoblastic leukemia

Comparative transcriptome analysis reveals compatible and recalcitrant genotypic response of barley microspore-derived embryogenic callus toward Agrobacterium infection

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