Molecular analysis of the t(15;17) translocation in acute promyelocytic leukaemia

Borrow, Julian; Solomon, Ellen

doi:10.1016/s0950-3536(11)80048-x

Cited by 14 publications

(3 citation statements)

References 226 publications

(275 reference statements)

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“…Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML) 1 . Cytogenetically, APL is characterized by a chromosomal t(15;17) translocation, which results in production of the oncogenic PML/RARα fusion protein 2 , 3 . Intensive studies of APL pathogenesis have resulted in several breakthroughs in the treatment of this disease.…”

Section: Introductionmentioning

confidence: 99%

Verteporfin Inhibits Cell Proliferation and Induces Apoptosis in Human Leukemia NB4 Cells without Light Activation

et al. 2017

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Background and Aims: Verteporfin (VP), clinically used in photodynamic therapy for neovascular macular degeneration, has recently been proven a suppressor of yes-associated protein (YAP) and has shown potential in anticancer treatment. However, its anti-human leukemia effects in NB4 cells remain unclear. In this study, we investigated the effects of VP on proliferation and apoptosis in human leukemia NB4 cells.Methods: NB4 cells were treated with VP for 24 h. The effects of VP on cell proliferation were determined using a Cell-Counting Kit-8 assay (CCK-8) assay and colony forming assay. Apoptosis and cell cycle were evaluated by flow cytometry (FCM). The protein levels were detected by western blot.Results: We found that VP inhibited the proliferation of NB4 cells in a concentration and time-dependent manner. FCM analysis showed that VP induced apoptosis in a concentration dependent manner and that VP treatment led to cell cycle arrest at G0/G1 phase. Moreover, VP significantly decreased the protein expression of YAP, p-YAP, Survivin, c-Myc, cyclinD1, p-ERK, and p-AKT. In addition, VP increased the protein expression of cleaved caspase3, cleaved PARP, Bax, and p-p38 MAPK.Conclusions: VP inhibited the proliferation and induced apoptosis in NB4 cells.

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Section: Introductionmentioning

confidence: 99%

Verteporfin Inhibits Cell Proliferation and Induces Apoptosis in Human Leukemia NB4 Cells without Light Activation

et al. 2017

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“…The fusion of the N-terminus of the PML, on chromosome 15, to the C-terminus of the RARA, on chromosome 17, explains APL pathogenesis in 95-98% of cases, resulting in the production of the biological hallmark of the disease: the PML/RARA rearrangement and the consequent oncogenic chimeric protein [5][6][7]. The prominent role of the rearrangement has been recently stressed by the updated 2016 WHO classification, which renamed this leukemia as "APL with PML-RARA" [8].…”

Section: Introductionmentioning

confidence: 99%

When Poisons Cure: The Case of Arsenic in Acute Promyelocytic Leukemia

Gurnari¹,

Bellis²,

Divona³

et al. 2019

Chemotherapy

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Arsenic has been known for centuries for its double-edged potential: a poison and at the same time a therapeutic agent. The name "arsenikon," meaning "potent," speaks itself for the pharmaceutical properties of this compound, questioned and analyzed for at least 2000 years. In the last decades, acute promyelocytic leukemia (APL) has evolved from a highly fatal to a curable disease, due to the use of all-transretinoic acid and, more recently, arsenic trioxide combinations. The success of these entirely chemo-free regimens increased the awareness of APL and reduced the prevalence of early deaths, which was an impending issue in this disease. Further improvements are expected with the next use of oral arsenic formulations, which will allow a complete outpatient approach, at least in the post-induction settings, further improving patients' quality of life. The wide use of standardized approaches in APL will also help unravel long-standing open questions, including the pathogenesis, prevention, and treatment of the differentiation syndrome and of short-term organ toxicities. In the long term, the study of survivorship issues, such as fertility and organ-related and psychological damages, in the increasing number of survivors will help further improve their life after APL.

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“…12 It has been proposed that PR␣ acts in a dominant-negative fashion to suppress the normal function of both PML and RAR␣. 13,14 Mouse models and cell culture experiments have demonstrated that PR␣ contributes to the leukemic phenotype mainly by inhibiting differentiation of hematopoietic progenitor cells.…”

Section: Introductionmentioning

confidence: 99%

Pim2 cooperates with PML-RARα to induce acute myeloid leukemia in a bone marrow transplantation model

Agrawal-Singh

Koschmieder

Gelsing

et al. 2010

Blood

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Although the potential role of Pim2 as a cooperative oncogene has been well described in lymphoma, its role in leukemia has remained largely unexplored. Here we show that high expression of Pim2 is observed in patients with acute promyelocytic leukemia (APL). To further characterize the cooperative role of Pim2 with promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha), we used a well-established PML-RARalpha (PRalpha) mouse model. Pim2 coexpression in PRalpha-positive hematopoietic progenitor cells (HPCs) induces leukemia in recipient mice after a short latency. Pim2-PRalpha cells were able to repopulate mice in serial transplantations and to induce disease in all recipients. Neither Pim2 nor PRalpha alone was sufficient to induce leukemia upon transplantation in this model. The disease induced by Pim2 overexpression in PRalpha cells contained a slightly higher fraction of immature myeloid cells, compared with the previously described APL disease induced by PRalpha. However, it also clearly resembled an APL-like phenotype and showed signs of differentiation upon all-trans retinoic acid (ATRA) treatment in vitro. These results support the hypothesis that Pim2, which is also a known target of Flt3-ITD (another gene that cooperates with PML-RARalpha), cooperates with PRalpha to induce APL-like disease.

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Molecular analysis of the t(15;17) translocation in acute promyelocytic leukaemia

Cited by 14 publications

References 226 publications

Verteporfin Inhibits Cell Proliferation and Induces Apoptosis in Human Leukemia NB4 Cells without Light Activation

Verteporfin Inhibits Cell Proliferation and Induces Apoptosis in Human Leukemia NB4 Cells without Light Activation

When Poisons Cure: The Case of Arsenic in Acute Promyelocytic Leukemia

Pim2 cooperates with PML-RARα to induce acute myeloid leukemia in a bone marrow transplantation model

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