Study of prognostic significance of marrow angiogenesis assessment in patients with de novo acute leukemia

Abdelaal, Amaal; Afify, Reham Abdel Aleem Mohamed; Zaher, Amr; El-Gammal, Mosaad M; Atef, Asmaa M

doi:10.1179/1607845415y.0000000012

Cited by 7 publications

(4 citation statements)

References 22 publications

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“…In the last few decades, a large number of studies show the involvement of angiogenesis in leukemogenesis as well as leukemia progression [28]. An increase in angiogenesis in the bone marrow niche is related to both acute lymphoblastic leukemia and acute myeloid leukemia [5][6][7][8][9]. erefore, targeting angiogenesis with antiangiogenic agents or VEGFR inhibitors is likely to be a new method for AML treatment.…”

Section: Discussionmentioning

confidence: 99%

“…In the last few years, a large number of studies have shown that angiogenesis is involved not only in leukemogenesis but also in leukemia progression [4]. An increased angiogenesis in the bone marrow niche relates to acute myeloid leukemia progression and resistance to treatment [5][6][7][8][9]. In consideration of the important role of angiogenic activity in di erent kinds of tumor-like hematological malignancies, targeting vasculogenesis signaling has gained more and more attention as a new therapy to avoid cancer metastasis and resistance.…”

Section: Introductionmentioning

confidence: 99%

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Synergistic Lethality Effects of Apatinib and Homoharringtonine in Acute Myeloid Leukemia

Shi

et al. 2022

Journal of Oncology

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Purpose. The significance of vascular endothelial growth factor receptor (VEGFR)-2 in numerous solid tumors and acute myeloid leukemia (AML) has been demonstrated, but Apatinib remains largely unexplored. In this study, whether Apatinib combined with homoharringtonine (HHT) kills AML cell lines and its possible mechanisms have been explored. Methods. AML cell lines were treated with Apatinib and HHT in different concentrations with control, Apatinib alone, HHT alone, and Apatinib combined with HHT. The changes of IC50 were measured by CCK8 assay, and apoptosis rate, cell cycle, and the mitochondrial membrane potential in each group were measured by flow cytometry. Finally, the possible cytotoxicity mechanism was analyzed by Western blotting. Results. Our results noted that Apatinib combined with HHT remarkably inhibited cell proliferation, reduced the capacity of colony-forming, and induced apoptosis and cell cycle arrest in AML cells. Mechanistically, Apatinib and HHT play a role as a suppressor in the expression of VEGFR-2 and the downstream signaling cascades, such as the PI3K, MAPK, and STAT3 pathways. Conclusion. Our preclinical data demonstrate that Apatinib combined with HHT exerts a better antileukemia effect than Apatinib alone by inhibiting the VEGFR-2 signaling pathway, suggesting the potential role of Apatinib and HHT in the treatment of AML. This study provides clinicians with innovative combination therapies and new therapeutic targets for the treatment of AML.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synergistic Lethality Effects of Apatinib and Homoharringtonine in Acute Myeloid Leukemia

Shi

et al. 2022

Journal of Oncology

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“…The observation of pro-apoptotic effects in both AML and CML cells broadens the potential of AD0157 as an apoptosis-inducing compound in myeloid leukemia cells. Although pathological angiogenesis was initially recognized as a hallmark of solid tumors, recent studies indicate that angiogenesis is also important in the pathogenesis and progression of several forms of leukemia, including AML and CML ( Molica et al, 2004 ; Trujillo et al, 2012 ; AbdElAal et al, 2015 ; Shirzad et al, 2016 ). The previously reported antiangiogenic activity of AD0157 altogether with data presented here, indicating a direct antileukemic effect of this compound by induction of apoptosis pathways, suggest that this natural compound could be a potential new agent for the treatment of myeloid leukemia.…”

Section: Discussionmentioning

confidence: 99%

The Natural Antiangiogenic Compound AD0157 Induces Caspase-Dependent Apoptosis in Human Myeloid Leukemia Cells

et al. 2017

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Evasion of apoptosis is a hallmark of cancer especially relevant in the development and the appearance of leukemia drug resistance mechanisms. The development of new drugs that could trigger apoptosis in aggressive hematological malignancies, such as AML and CML, may be considered a promising antileukemic strategy. AD0157, a natural marine pyrrolidinedione, has already been described as a compound that inhibits angiogenesis by induction of apoptosis in endothelial cells. The crucial role played by defects in the apoptosis pathways in the pathogenesis, progression and response to conventional therapies of several forms of leukemia, moved us to analyze the effect of this compound on the growth and death of leukemia cells. In this work, human myeloid leukemia cells (HL60, U937 and KU812F) were treated with AD0157 ranging from 1 to 10 μM and an experimental battery was applied to evaluate its apoptogenic potential. We report here that AD0157 was highly effective to inhibit cell growth by promotion of apoptosis in human myeloid leukemia cells, and provide evidence of its mechanisms of action. The apoptogenic activity of AD0157 on leukemia cells was verified by an increased chromatin condensation and DNA fragmentation, and confirmed by an augmentation in the apoptotic subG1 population, translocation of the membrane phosphatidylserine from the inner face of the plasma membrane to the cell surface and by cleavage of the apoptosis substrates PARP and lamin-A. In addition, AD0157 in the low micromolar range significantly enhanced the activities of the initiator caspases-8 and -9, and the effector caspases-3/-7 in a dose-dependent manner. Results presented here throw light on the apoptogenic mechanism of action of AD0157, mediated through caspase-dependent cascades, with an especially relevant role played by mitochondria. Altogether, these results suggest the therapeutic potential of this compound for the treatment of human myeloid leukemia.

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“…The quantity of blood vessels in leukemia patients is usually referred to as microvessel density (MVD). 68 which is used as a prognostic factor associated with poor prognosis. The higher MVD, the higher disease relapse risk that is associated with lower survival rate of patients.…”

Section: The Vessel and Angiogenesis In Leukemiamentioning

confidence: 99%

Bone marrow blood vessels: normal and neoplastic niche

et al. 2016

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Blood vessels are among the most important factors in the transport of materials such as nutrients and oxygen. This study will review the role of blood vessels in normal bone marrow hematopoiesis as well as pathological conditions like leukemia and metastasis. Relevant literature was identified by a Pubmed search (1992-2016) of English-language papers using the terms bone marrow, leukemia, metastasis, and vessel. Given that blood vessels are conduits for the transfer of nutrients, they create a favorable situation for cancer cells and cause their growth and development. On the other hand, blood vessels protect leukemia cells against chemotherapy drugs. Finally, it may be concluded that the vessels are an important factor in the development of malignant diseases.

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Study of prognostic significance of marrow angiogenesis assessment in patients with de novo acute leukemia

Abstract: The study demonstrated an evidence of increased angiogenesis in acute leukemia detected by high bone marrow MVD which may play a significant role in leukemic process. Understanding its role may help in designing new therapeutic strategies for acute leukemia.

Cited by 7 publications

References 22 publications

Synergistic Lethality Effects of Apatinib and Homoharringtonine in Acute Myeloid Leukemia

Synergistic Lethality Effects of Apatinib and Homoharringtonine in Acute Myeloid Leukemia

The Natural Antiangiogenic Compound AD0157 Induces Caspase-Dependent Apoptosis in Human Myeloid Leukemia Cells

Bone marrow blood vessels: normal and neoplastic niche

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