The role of PML in hematopoietic and leukemic stem cell maintenance

Nakahara, Fumio; Weiss, Cary N.; Ito, Keisuke

doi:10.1007/s12185-014-1518-x

Cited by 17 publications

(15 citation statements)

References 59 publications

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“…The PML-RARα fusion protein is found in approximately 98% of patients with APL [37], so many APL treatments are designed to disrupt or inhibit PML-RARα downstream signaling [1]. A major treatment modality is all-trans retinoic acid (ATRA) therapy, which is a natural ligand for RARs.…”

Section: Discussionmentioning

confidence: 99%

Sumoylation of the Tumor Suppressor Promyelocytic Leukemia Protein Regulates Arsenic Trioxide-Induced Collagen Synthesis in Osteoblasts

Liu

et al. 2015

Cell Physiol Biochem

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Background/Aims: Promyelocytic leukemia (PML) protein is a tumor suppressor that fuses with retinoic acid receptor-α (PML-RARα) to contribute to the initiation of acute promyelocytic leukemia (APL). Arsenic trioxide (ATO) upregulates expression of TGF-β1, promoting collagen synthesis in osteoblasts, and ATO binds directly to PML to induce oligomerization, sumoylation, and ubiquitination. However, how ATO upregulates TGF-β1 expression is uncertain. Thus, we suggested that PML sumoylation is responsible for regulation of TGF-β1 protein expression. Methods: Kunming mice were treated with ATO, and osteoblasts were counted under scanning electron microscopy. Masson's staining was used to quantify collagen content. hFOB1.19 cells were transfected with siRNA against UBC9 or RNF4, and then treated with ATO or FBS. TGF-β1, PML expression, and sumoylation were quantified with Western blot, and collagen quantified via immunocytochemistry. Results: ATO enhanced osteoblast accumulation, collagen synthesis, and PML-NB formation in vivo. Knocking down UBC9 in hFOB1.19 cells inhibited ATO- and FBS-induced PML sumoylation, TGF-β1 expression, and collagen synthesis. Conversely, knocking down RNF4 enhanced ATO- and FBS-induced PML sumoylation, TGF-β1 expression, and collagen synthesis. Conclusion: These data suggest that PML sumoylation is required for ATO-induced collagen synthesis in osteoblasts.

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Section: Discussionmentioning

confidence: 99%

Sumoylation of the Tumor Suppressor Promyelocytic Leukemia Protein Regulates Arsenic Trioxide-Induced Collagen Synthesis in Osteoblasts

Liu

et al. 2015

Cell Physiol Biochem

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“…PML is an essential regulator of somatic cell programming and stem cell pluripotency [348]. PML has diverse functions that regulate: response to DNA damage, apoptosis, senescence, and angiogenesis [349,350]. PML is a regulator of metabolic pathways in stem cell compartments including hematopoietic system and it has provided new strategies for controlling stem cell maintenance and differentiation [349].…”

Section: Promyelocytic Leukemia Proteinmentioning

confidence: 99%

“…PML has diverse functions that regulate: response to DNA damage, apoptosis, senescence, and angiogenesis [349,350]. PML is a regulator of metabolic pathways in stem cell compartments including hematopoietic system and it has provided new strategies for controlling stem cell maintenance and differentiation [349]. For its action, PML recruits other proteins such as: Sp100, Daxx, small ubiquitinlike modi ier (SUMO)-1, CBP, and P53 [350].…”

Section: Promyelocytic Leukemia Proteinmentioning

confidence: 99%

“…The various elements that are implicated in VZV infections are illustrated in igure 3. [101,[204][205][206][207]245,248,268,[272][273][274]276,292,[304][305][306][307][310][311][312][313][320][321][322][323][324]334,341,[343][344][345][346]349,350,361,[368][369][370][371]378,381,387,[397][398][399][400][401][402][403][404]…”

Section: Other Signaling Pathways In Vzv Infectionmentioning

confidence: 99%

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The beneficial effects of varicella zoster virus

Al-Anazi¹,

Wk²,

Al-Jasser³

2019

J Hematol Clin Res

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Varicella zoster virus behaves differently from other herpes viruses as it differs from them in many aspects. Recently, there has been growing evidence on the benefi cial effects of the virus in immune compromised hosts and these effects are translated into prolongation of survival. The reported benefi cial effects of the virus include: (1) stimulation of bone marrow activity in patients with hematologic malignancies and bone marrow failure syndromes, (2) antitumor effects in various hematologic malignancies and solid tumors, and (3) association with graft versus host disease which has anticancer effects. Additionally, there are several reports on the safety of the live-attenuated even in severely immune suppressed individuals and on the emerging role of the virus in cancer immunotherapy. In this review, the following aspects of the virus will be thoroughly discussed: (1) new data on the genetic background, pathogenesis, vaccination, and new therapeutic modalities; (2) bone marrow microenvironment and hematopoiesis; (3) cells involved in the pathogenesis of the virus such as: mesenchymal stem cells, dendritic cells, natural killer cells, T-cells and mononuclear cells; (4) cellular proteins such as open reading frames, glycoproteins, promyelocytic leukemia protein, chaperons, and SUMOs; (5) extracellular vesicles, exosomes, and micro-RNAs; and (6) signaling pathways, cytokines, and interferons.

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“…The tumor suppressor PML plays an essential role in the regulation of CML stem cell [ 63 ], and various reviews have been published on this topic [ 64 , 65 ]. Furthermore, PML plays an essential role in the regulation of the tumor suppressive function of PTEN, through HAUSP [ 66 ].…”

Section: Tumor Suppressors Involved In CML Pathogenesis Not Directlmentioning

confidence: 99%

The non-genomic loss of function of tumor suppressors: an essential role in the pathogenesis of chronic myeloid leukemia chronic phase

et al. 2016

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BackgroundChronic Myeloid Leukemia was always referred as a unique cancer due to the apparent independence from tumor suppressors’ deletions/mutations in the early stages of the disease. However, it is now well documented that even genetically wild-type tumor suppressors can be involved in tumorigenesis, when functionally inactivated. In particular, tumor suppressors’ functions can be impaired by subtle variations of protein levels, changes in cellular compartmentalization and post-transcriptional/post-translational modifications, such as phosphorylation, acetylation, ubiquitination and sumoylation. Notably, tumor suppressors inactivation offers challenging therapeutic opportunities. The reactivation of an inactive and genetically wild-type tumor suppressor could indeed promote selective apoptosis of cancer cells without affecting normal cells.Main bodyChronic Myeloid Leukemia (CML) could be considered as the paradigm for non-genomic loss of function of tumor suppressors due to the ability of BCR-ABL to directly promote functionally inactivation of several tumor suppressors.Short conclusionIn this review we will describe new insights on the role of FoxO, PP2A, p27, BLK, PTEN and other tumor suppressors in CML pathogenesis. Finally, we will describe strategies to promote tumor suppressors reactivation in CML.

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The role of PML in hematopoietic and leukemic stem cell maintenance

Cited by 17 publications

References 59 publications

Sumoylation of the Tumor Suppressor Promyelocytic Leukemia Protein Regulates Arsenic Trioxide-Induced Collagen Synthesis in Osteoblasts

Sumoylation of the Tumor Suppressor Promyelocytic Leukemia Protein Regulates Arsenic Trioxide-Induced Collagen Synthesis in Osteoblasts

The beneficial effects of varicella zoster virus

The non-genomic loss of function of tumor suppressors: an essential role in the pathogenesis of chronic myeloid leukemia chronic phase

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