Using PU.1 and Jun dimerization protein 2 transcription factor expression in myelodysplastic syndromes to predict treatment response and leukaemia transformation

Boasman, Kristian; Simmonds, Matthew J.; Graham, Ciaren; Saunthararajah, Yogen; Rinaldi, Ciro R.

doi:10.1007/s00277-019-03627-9

Cited by 5 publications

(4 citation statements)

References 8 publications

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“…Of note, ANP32B binds to the DNA-binding domain of PU.1, whereas binds to the C-terminal domain (CTD) of p53. The mechanisms of ANP32B acting as a coactivator for PU.1 or a corepressor for p53 need to be further addressed.PU.1 plays crucial roles in the determination and differentiation of hematopoietic lineages,46,47 and is associated with the occurrence of erythrocyte leukemia, pre-B-ALL, acute myeloid leukemia, and other diseases [48][49][50]. Here, we used cell lines and mouse models to demonstrate that PU.1 overexpression dramatically suppresses B-ALL progression, which is consistent with the tumor suppressor function in B-ALL revealed by PU.1 and Spi-B double deletion.…”

supporting

confidence: 75%

“…PU.1 plays crucial roles in the determination and differentiation of hematopoietic lineages, 46 , 47 and is associated with the occurrence of erythrocyte leukemia, pre‐B‐ALL, acute myeloid leukemia, and other diseases. 48 , 49 , 50 Here, we used cell lines and mouse models to demonstrate that PU.1 overexpression dramatically suppresses B‐ALL progression, which is consistent with the tumor suppressor function in B‐ALL revealed by PU .…”

Section: Discussionmentioning

confidence: 99%

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ANP32B suppresses B‐cell acute lymphoblastic leukemia through activation of PU.1 in mice

et al. 2023

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ANP32B, a member of the acidic leucine‐rich nuclear phosphoprotein 32 kDa (ANP32) family of proteins, is critical for normal development because its constitutive knockout mice are perinatal lethal. It is also shown that ANP32B acts as a tumor‐promoting gene in some kinds of cancer such as breast cancer and chronic myelogenous leukemia. Herein, we observe that ANP32B is lowly expressed in B‐cell acute lymphoblastic leukemia (B‐ALL) patients, which correlates with poor prognosis. Furthermore, we utilized the N‐myc or BCR‐ABLp190‐induced B‐ALL mouse model to investigate the role of ANP32B in B‐ALL development. Intriguingly, conditional deletion of Anp32b in hematopoietic cells significantly promotes leukemogenesis in two B‐ALL mouse models. Mechanistically, ANP32B interacts with purine rich box‐1 (PU.1) and enhances the transcriptional activity of PU.1 in B‐ALL cells. Overexpression of PU.1 dramatically suppresses B‐ALL progression, and highly expressed PU.1 significantly reverses the accelerated leukemogenesis in Anp32b‐deficient mice. Collectively, our findings identify ANP32B as a suppressor gene and provide novel insight into B‐ALL pathogenesis.

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supporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

ANP32B suppresses B‐cell acute lymphoblastic leukemia through activation of PU.1 in mice

et al. 2023

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“…Further studies can directly address the dynamics of PU.1, NF-κB and CEBPA in response to inflammatory cues in HSC and their downstream progenitors. Moreover, several other transcriptional regulators interact with PU.1, including AP-1 family transcription factors ( Steidl et al, 2006 ; Boasman et al, 2019 ; Zhao et al, 2022 ). Indeed, the AP-1 factors c-Jun and JunB are also critical interacting partners with PU.1 that also regulate myeloid differentiation (including PU.1 expression) ( Steidl et al, 2006 ; Raghav et al, 2018 ; Zhao et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

PU.1 is required to restrain myelopoiesis during chronic inflammatory stress

Rabe

Niño

Wells

et al. 2023

Front. Cell Dev. Biol.

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Chronic inflammation is a common feature of aging and numerous diseases such as diabetes, obesity, and autoimmune syndromes and has been linked to the development of hematological malignancy. Blood-forming hematopoietic stem cells (HSC) can contribute to these diseases via the production of tissue-damaging myeloid cells and/or the acquisition of mutations in epigenetic and transcriptional regulators that initiate evolution toward leukemogenesis. We previously showed that the myeloid “master regulator” transcription factor PU.1 is robustly induced in HSC by pro-inflammatory cytokines such as interleukin (IL)-1β and limits their proliferative activity. Here, we used a PU.1-deficient mouse model to investigate the broader role of PU.1 in regulating hematopoietic activity in response to chronic inflammatory challenges. We found that PU.1 is critical in restraining inflammatory myelopoiesis via suppression of cell cycle and self-renewal gene programs in myeloid-biased multipotent progenitor (MPP) cells. Our data show that while PU.1 functions as a key driver of myeloid differentiation, it plays an equally critical role in tailoring hematopoietic responses to inflammatory stimuli while limiting expansion and self-renewal gene expression in MPPs. These data identify PU.1 as a key regulator of “emergency” myelopoiesis relevant to inflammatory disease and leukemogenesis.

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“…Interest in CD47 is increasing and it is thought to be a promising target for cancer therapy. Research on CD47 in cancer has revealed that many malignancies express high quantities of CD47 on their surface, which shields the cancer cells from phagocytosis by macrophages and helps them avoid immunity surveillance (10).According to Elade et al (2020) cancer cells frequently exhibit and overexpress CD47 in an effort to fight against phagocytosis (11),. According to studies specifically on MDS, suppressing the CD47 signal causes MDS cells to be selectively phagocytosed because it reduces their "don't eat me" signal (12).…”

Section: Introductionmentioning

confidence: 99%

Investigating the role of CD47 gene regulation in Iraqi cancer patients: a promising prognostic factor

Jabbar,

Ismael

2023

Iraqi j. cancer med. genet.

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Background: Innate immune checkpoints have been one of the most studied and promising approaches in cancer immune therapy. Therefore, it is considered valuable when investigating these checkpoints at the gene expression and protein levels. However, this approach still has variations from study to study due to various types of cancer. Therefore, it is hypothesized that CD47 could be one of those checkpoints that affect the survival of cancer cells. CD47 is an integrin like marker that has been identified for its role as “do not eat me signal” which enhances the ability of cancer cells to escape from being phagocytized by macrophages. Aim of the study: This study aims to investigate CD47 expression in ten solid tumors and five blood cancers at the gene level and at the protein level.Methods: Clinical specimens were collected from patients with different cancers attending Kirkuk oncology center. The patients were categorized into two main groups: solid tumor group and blood-derived cancer group together with their control counterparts. CD47 gene expression was investigated using q RT-PCR techniques while its protein levels were investigated using ELISA techniques.Results: The results showed a significant up-regulation of CD47 gene expression in gastric cancer, cholangiocarcinoma; CCA (bile duct), chronic myeloid leukemia (CML), and breast cancer, respectively. These results were also confirmed at the protein level, suggesting that those types of malignancy are more susceptible to an increase in CD47 expression than other types of cancer that were involved in this study. Conclusion: CD47 tends to be over-expressed in solid tumors and blood cancers, and could be used as diagnostic and prognostic markers, especially for solid tumors.

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Using PU.1 and Jun dimerization protein 2 transcription factor expression in myelodysplastic syndromes to predict treatment response and leukaemia transformation

Cited by 5 publications

References 8 publications

ANP32B suppresses B‐cell acute lymphoblastic leukemia through activation of PU.1 in mice

ANP32B suppresses B‐cell acute lymphoblastic leukemia through activation of PU.1 in mice

PU.1 is required to restrain myelopoiesis during chronic inflammatory stress

Investigating the role of CD47 gene regulation in Iraqi cancer patients: a promising prognostic factor

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