Angiogenesis in Acute Myeloid Leukemia and Opportunities for Novel Therapies

Trujillo, Angelica; McGee, Christie; Cogle, Christopher R.

doi:10.1155/2012/128608

Cited by 52 publications

(42 citation statements)

References 53 publications

(54 reference statements)

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“…6,7 Recent studies on the pathogenesis of AML showed that genetic disorder had the most important role in determining the response to chemotherapy and outcomes, which lead to the incorporation of targeted therapy into the standard treatment and open a new exciting era in AML therapy. Emerging agents include Gemtuzumab ozagamicin-targeting CD33, 8 histone deacetylase 9,10 and proteosome inhibitors, 11 antiangiogenesis agents, 12 Fms-like tyrosine kinase 3 inhibitors 9,13,14 and so on. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression in the posttranscriptional level, [15][16][17] which have been identified as crucial regulators in normal and malignant biological processes.…”

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confidence: 99%

The role, mechanism and potentially therapeutic application of microRNA-29 family in acute myeloid leukemia

et al. 2013

Cell Death Differ

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Abnormal proliferation, apoptosis repression and differentiation blockage of hematopoietic stem/progenitor cells have been characterized to be the main reasons leading to acute myeloid leukemia (AML). Previous studies showed that miR-29a and miR-29b could function as tumor suppressors in leukemogenesis. However, a comprehensive investigation of the function and mechanism of miR-29 family in AML development and their potentiality in AML therapy still need to be elucidated. Herein, we reported that the family members, miR-29a, -29b and -29c, were commonly downregulated in peripheral blood mononuclear cells and bone marrow (BM) CD34 þ cells derived from AML patients as compared with the healthy donors. Overexpression of each miR-29 member in THP1 and NB4 cells markedly inhibited cell proliferation and promoted cell apoptosis. AKT2 and CCND2 mRNAs were demonstrated to be targets of the miR-29 members, and the role of miR-29 family was attributed to the decrease of Akt2 and CCND2, two key signaling molecules. Significantly increased Akt2, CCND2 and c-Myc levels in the AML cases were detected, which were correlated with the decreased miR-29 expression in AML blasts. Furthermore, a feed-back loop comprising of c-Myc, miR-29 family and Akt2 were found in myeloid leukemogenesis. Reintroduction of each miR-29 member partially corrected abnormal cell proliferation and apoptosis repression and myeloid differentiation arrest in AML BM blasts. An intravenous injection of miR-29a, -29b and -29c in the AML model mice relieved leukemic symptoms significantly. Taken together, our finding revealed a pivotal role of miR-29 family in AML development and rescue of miR-29 family expression in AML patients could provide a new therapeutic strategy.

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confidence: 99%

The role, mechanism and potentially therapeutic application of microRNA-29 family in acute myeloid leukemia

et al. 2013

Cell Death Differ

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“…AML is a hematological malignancy of the bone marrow characterized by a mutation in hematopoietic stem or progenitor cells, which develops into a highly proliferative accumulation of dysfunctional and immature myeloid cells (2). When interpreting studies on CECs and EPCs, attention must be paid to the different definitions and phenotypic characterization of CECs in each study, due to the lacking of a universal definition of these cell population (16), and to the different methods of CECs and EPCs detection, such as flow cytometry and the CELLSEARCH ® system (16).…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, there has been an increased understanding of the role of angiogenesis in the progression of AML (2). Although circulating endothelial cells (CECs) and their progenitors, endothelial progenitor cells (EPCs), were first described >30 years ago through light microscopy, the development of specific monoclonal antibodies against these cells has only recently provided the opportunity to investigate the pathophysiology of these cells (3).…”

Section: Introductionmentioning

confidence: 99%

Circulating endothelial cells and their progenitors in acute myeloid leukemia

et al. 2016

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Abstract. Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by the accumulation of immature myeloid progenitor cells in the bone marrow. Studies are required to investigate the prognostic and predictive value of surrogate biomarkers. Given the importance of angiogenesis in oncology in terms of pathogenesis as well as being a target for treatment, circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) are promising candidates to serve as such markers. The aim of the present study was to quantify CECs and EPCs in patients with AML at initial diagnosis and following induction chemotherapy, and to correlate these findings with the response to treatment in AML patients. The present study included 40 patients with de novo AML and 20 age-and gender-matched healthy controls. CECs and EPCs were evaluated by flow cytometry at initial diagnosis and after induction chemotherapy (3+7 protocol for AML other than M3 and all-trans-retinoic acid plus anthracycline for M3 disease). CECs and EPCs were significantly higher in AML patients at diagnosis and after induction chemotherapy than in controls. After induction chemotherapy, CECs and EPCs were significantly decreased compared with the levels at initial diagnosis. Patients who achieved complete response (n=28) had lower initial CEC and EPC levels compared with patients who did not respond to treatment. These results suggest that CEC levels are higher in AML patients and may correlate with disease status and treatment response. Further investigations are required to better determine the predictive value and implication of these cells in AML management.

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“…Angiogenesis seems to be important for both leukemogenesis and susceptibility to intensive chemotherapy, and antiangiogenic strategies are therefore now being considered for the treatment of AML. [33][34][35] Though recently other mechanisms of action have also been reported, metronomic therapies are believed to work primarily through antiangiogenic mechanisms. [6,7] For the large group of elderly patients affected, intensive strategies are not possible because of high treatment-related mortality.…”

Section: Discussionmentioning

confidence: 99%

Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia? A literature review

et al. 2013

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Acute myeloid leukemia (AML) in older adults differs biologically and clinically from that in younger patients and is characterized by adverse chromosomal abnormalities, stronger intrinsic resistance, and lower tolerance to chemotherapy. In patients over age 60 with AML, cure rates are under 10% despite intensive chemotherapy, and most of them die within a year of diagnosis. Over the last decade, metronomic chemotherapy has emerged as a potential strategy to control advanced/refractory cancer. Here, we report a case of a 68-year-old gentleman having AML with high-risk cytogenetic features, who achieved complete remission on our oral metronomic PrET (PrET: Prednisolone, etoposide, thioguanine) protocol on an outpatient basis. He was later treated with standard high-dose (HD) cytosine arabinoside (Ara-C) consolidation followed by maintenance with etoposide, thioguanine, and sodium valproate. Presently, the patient is nearly 35 months since diagnosis and 21 months off treatment. This case report and review highlights that the combination of oral low-intensity metronomic therapy, followed by standard HD consolidation therapy and metronomic maintenance therapy may be well tolerated by elderly patients especially with less proliferative, high (cytogenetic)-risk AML who are otherwise deemed to be unfit for intensive intravenous induction chemotherapy regimens. References for this review were identified through searches of Pubmed for recent publications on the subject as well as searches of the files of the authors themselves. The final list was generated on the basis of originality and relevance to this review.

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Angiogenesis in Acute Myeloid Leukemia and Opportunities for Novel Therapies

Cited by 52 publications

References 53 publications

The role, mechanism and potentially therapeutic application of microRNA-29 family in acute myeloid leukemia

The role, mechanism and potentially therapeutic application of microRNA-29 family in acute myeloid leukemia

Circulating endothelial cells and their progenitors in acute myeloid leukemia

Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia? A literature review

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