Progress in the treatment of acute promyelocytic leukemia: optimization and obstruction

Jm, Li; Zhu, Hongming; Hu, Jiong; Mi, Jian-Qing; Chen, Sai‐Juan; Zhu, Cairong; Wang, Zhenyi

doi:10.1007/s12185-014-1603-1

Cited by 20 publications

(15 citation statements)

References 72 publications

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“…Acute promyelocytic leukemia (APL) is a subtype of AML characterized by a promyelocytic leukemia‐retinoic acid receptor α(PML‐RARa)‐mediated differentiation block at the promyelocyte stage, which occurs (at least in part) through an impairment in C/EBPα function . This block is reversed by all‐trans retinoic acid (ATRA), which is used as frontline therapy for APL . After the start of ATRA treatment, mature neutrophil‐like cells originate from leukemic promyelocytes and their numbers increase in the bone marrow and peripheral blood of responder APL cases.…”

Section: Role Of Cebpβ In Other Hematological Malignanciesmentioning

confidence: 99%

Non‐steady‐state hematopoiesis regulated by the C/EBPβ transcription factor

et al. 2015

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Steady-state hematopoiesis responds to extracellular stimuli to meet changing demands and also to pathologically altered intracellular signaling. Granulocyte production increases following infection or in response to cytokine stimulation, and activation of the CCAAT/enhancer-binding protein β (C/EBPβ) transcription factor is required for such stress-induced granulopoiesis, whereas C/EBPα plays a critical role in maintaining steady-state granulopoiesis. Different roles of these C/EBP transcription factors in different modes of hematopoiesis are evolutionally conserved from zebrafish to humans. In addition to reactions against infections, C/EBPβ is responsible for cancer-driven myelopoiesis, which promotes cancer progression, at least in part, by abrogating the immune response in the cancer microenvironment. The BCR–ABL fusion protein activates emergency-specific pathway of granulopoiesis by upregulating C/EBPβ. This in turn causes chronic phase chronic myeloid leukemia, which is characterized by myeloid expansion. The C/EBPβ transcription factor also plays a role in other hematological malignancies of both myeloid and lymphoid lineage origin. Thus, elucidation of the upstream and downstream networks surrounding C/EBPβ will lead to the development of novel therapeutic strategies for diseases mediated by non-steady-state hematopoiesis.

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Section: Role Of Cebpβ In Other Hematological Malignanciesmentioning

confidence: 99%

Non‐steady‐state hematopoiesis regulated by the C/EBPβ transcription factor

et al. 2015

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“…Conventional chemotherapy, using cytotoxic drugs to inhibit the proliferation of malignant cells or destroy malignant cells, has become the most common and primary clinical strategy in the treatment of blood malignancies. The targeted chemotherapeutic drugs, such as the first FDA-approved tyrosine kinase inhibitor (TKI) imatinib has been used for treating chronic myeloid leukemia (CML) patients with oncoprotein BCR-ABL expression, which has resulted in well-pleasing and remarkable treatment outcomes for the majority of CML patients [1-3]. Unfortunately, multidrug resistance (MDR) is still the main reason for the failure and relapse of leukemia chemotherapy using conventional or targeted chemotherapeutic drugs.…”

Section: Introductionmentioning

confidence: 99%

Ceritinib Enhances the Efficacy of Substrate Chemotherapeutic Agent in Human ABCB1-Overexpressing Leukemia Cells In Vitro, In Vivo and Ex-Vivo

Yang

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Multidrug resistance (MDR) triggered by ATP binding cassette (ABC) transporters, such as ABCB1, ABCC1, and ABCG2, is a key obstacle for successful cancer chemotherapy. There is currently no FDA-approved MDR modulator that can be used in clinic. Ceritinib, a selective ALK inhibitor, has been approved as the second-line treatment for ALK-positive non-small cell lung cancer. Here, we examined the role of ceritinib in leukemia associated MDR in therapy. Methods: The cell proliferation was detected by MTT assay. The flow cytometry was used to detect the expression of cell surface protein and to detect the accumulation and efflux of rhodamine 123 (Rh123) or doxorubicin (Dox) in cells. The RT-PCR and Western blot were performed to detect the gene expression and protein expression levels, respectively. Results: We found that ceritinib enhanced the efficacy of substrate chemotherapeutic agent in ABCB1-overexpressing K562/adr leukemia cells both in vitro and in vivo models, but neither in sensitive parental K562 leukemia cells nor in ABCC1-overexpressing HL-60/adr leukemia cells. Mechanistically, ceritinib significantly increased the intracellular accumulation of Rh123 or Dox but did neither alter ABCB1 expressions at both protein and mRNA levels nor block the phosphorylations of AKT and ERK1/2 at the concentration of MDR reversal. Importantly, ceritinib also increased the intracellular accumulation of Dox and enhanced the efficacy of Dox in primary leukemia cells in ex-vivo. Conclusion: Our results suggested that ceritinib enhanced the efficacy of substrate chemotherapeutic agent on inhibition of leukemia cell growth in vitro, in vivo and ex-vivo, which linked to block ABCB1 function, pumping out its substrate conventional chemotherapeutic agent, thereby increasing the intracellular accumulation. These suggest the combination of ceritinib and substrate chemotherapeutic drugs maybe an effective treatment of resistant leukemia patients with ABCB1-mediated MDR.

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“…A routine approach for AML treatment is chemotherapy 15 , however, this method is affected by the resistance that decreases the treatment efficiency in many cases, as it is frequently exemplified by resistance to ATRA 16,17 . In addition, the combination of cancer cells, and oncogenic lncRNA inhibitors, are more sensitive to chemotherapy agents, compared to each alone 18 .…”

Section: Discussionmentioning

confidence: 99%

The Effect of Inhibition of Lncrna Mir100hg on the Proliferation of Human Promyelocytic Leukemia Cells

Bagheri

Sharifi

Salehi

2019

Int J Life Sci Pharm Res

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lncRNAs are one of the main classes of non-coding RNAs, responsible for RNA regulation in a variety of cellular processes, and their effect on human cancer remains largely unexplored; Abnormal expression of lncRNAs has been shown to be associated with many human diseases and cancers, such as leukemia. Acute promyelocytic leukemia (APL) is the M3 subtype of acute myeloid leukemia (AML), with the aberrant accumulation of promyelocytes. One of the lncRNAs that showed upregulation in AML is lncRNA MIR100HG, involved in different cancers. The aim of our study is to investigate the functional role of MIR100HG antisense LNA GapmeRs, on APL cells. In this experimental study, we have used an Antisense LNA GapmeRs, in order to block MIR100HG in APL Cells. HL60 (APL cell line) cells were transfected with MIR100HG antisense LNA GapmeRs and at three different time points (24, 48 and 72 h) and were investigated apoptosis, necrosis, MIR100HG and TGFβ expression. MIR100HG inhibition could reduce the viability of HL-60 cells, through induction of apoptosis; because of the TGFβ upregulation. qRT-PCR was performed to determine the MIR100HG expression by antisense LNA GapmeRs. Our results suggest that degradation of MIR100HG could serve as a novel approach for controlling the proliferation of APL cells and therefore, can be used in translational medicine for targeted therapy in APL.

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Progress in the treatment of acute promyelocytic leukemia: optimization and obstruction

Cited by 20 publications

References 72 publications

Non‐steady‐state hematopoiesis regulated by the C/EBPβ transcription factor

Non‐steady‐state hematopoiesis regulated by the C/EBPβ transcription factor

Ceritinib Enhances the Efficacy of Substrate Chemotherapeutic Agent in Human ABCB1-Overexpressing Leukemia Cells In Vitro, In Vivo and Ex-Vivo

The Effect of Inhibition of Lncrna Mir100hg on the Proliferation of Human Promyelocytic Leukemia Cells

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