Acute Myeloid Leukaemia

Villela, Luís; Bolaños-Meade, Javier

doi:10.2165/11593060-000000000-00000

Cited by 21 publications

(12 citation statements)

References 109 publications

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“…To assess the clearance of dead cells, we studied patients undergoing myeloablative therapy for AML and B-ALL, which causes massive death of BM cells (27). BM from a child with B-ALL exhibited 100% cellularity prior to myeloablative therapy, but 8-days later was hypocellular (<5% cellularity) with erythroid regeneration (Fig.…”

Section: Resultsmentioning

confidence: 99%

A Novel Subset of Anti-Inflammatory CD138+ Macrophages Is Deficient in Mice with Experimental Lupus

Han

Zhuang

Shumyak

et al. 2017

The Journal of Immunology

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Dead cells accumulating in the tissues may contribute to chronic inflammation. We examined the cause of impaired apoptotic cell clearance human and murine lupus. Dead cells accumulated in bone marrow from lupus patients but not from non-autoimmune patients undergoing myeloablation, where they were efficiently removed by macrophages. Impaired apoptotic cell uptake by macrophages also was seen in mice treated i.p. with pristane (develop lupus) but not mineral oil (MO, do not develop lupus). The inflammatory response to both pristane and MO rapidly depleted resident (Tim4+) large peritoneal macrophages (LPM). The peritoneal exudate of pristane-treated mice contained mainly Ly6Chi inflammatory monocytes, whereas in MO-treated mice, it consisted predominantly of a novel subset of highly phagocytic macrophages resembling small peritoneal macrophages (SPM) that expressed CD138+ and the scavenger receptor Marco. Treatment with anti-Marco neutralizing antibodies and the class A scavenger receptor antagonist polyinosinic acid inhibited phagocytosis of apoptotic cells by CD138+ macrophages. CD138+ macrophages expressed IL-10 receptor, CD206, and CCR2 but little TNFα or CX3CR1. They also expressed high levels of activated CREB, a transcription factor implicated in generating alternatively activated macrophages. Similar cells were identified in the spleen and lung of MO-treated mice and also were induced by lipopolysaccharide. We conclude that highly phagocytic, CD138+ SPM-like cells with an anti-inflammatory phenotype may promote the resolution of inflammation in lupus and infectious diseases. These SPM-like cells are not restricted to the peritoneum, and may help clear apoptotic cells from tissues such as the lung, helping to prevent chronic inflammation.

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Section: Resultsmentioning

confidence: 99%

A Novel Subset of Anti-Inflammatory CD138+ Macrophages Is Deficient in Mice with Experimental Lupus

Han

Zhuang

Shumyak

et al. 2017

The Journal of Immunology

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“…Flavopiridol has been used in a group of relapsed/refractory or de novo acute myeloid leukemia patients with a combination regimen known as FLAM (flavopiridol, cytarabine and mitoxantrone) with favorable outcomes and low toxicity. Flavopiridol is one of the novel agents and is also currently under clinical investigation with expectations at the treatment outcomes for chronic lymphocytic leukemia ( 23 , 24 ). The present study is the first, to the best of our knowledge, to evaluate the effects of flavopiridol in CSCs.…”

Section: Discussionmentioning

confidence: 99%

Induced growth inhibition, cell cycle arrest and apoptosis in CD133+/CD44+ prostate cancer stem cells by flavopiridol

Soner

Aktuğ

Açıkgöz

et al. 2014

International Journal of Molecular Medicine

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Flavopiridol is a flavone that inhibits several cyclin-dependent kinases and exhibits potent growth-inhibitory activity, apoptosis and G1-phase arrest in a number of human tumor cell lines. Flavopiridol is currently undergoing investigation in human clinical trials. The present study focused on the effect of flavopiridol in cell proliferation, cell cycle progression and apoptosis in prostate cancer stem cells (CSCs). Therefore, cluster of differentiation 133 (CD133)+high/CD44+high prostate CSCs were isolated from the DU145 human prostate cancer cell line. The cells were treated with flavopiridol in a dose- and time-dependent manner to determine the inhibitory effect. Cell viability and proliferation were analyzed and the efficiency of flavopiridol was assessed using the sphere-forming assay. Flavopiridol was applied to monolayer cultures of CD133high/CD44high human prostate CSCs at the following final concentrations: 100, 300, 500 and 1000 nM. The cultures were incubated for 24, 48 and 72 h. The half maximal inhibitory concentration (IC50) value of the drug was determined as 500 nM for monolayer cells. Dead cells were analyzed prior and subsequent to exposure to increasing flavopiridol doses. Annexin-V and immunofluorescence analyses were performed for the evaluation of apoptotic pathways. According to the results, flavopiridol treatment caused significant growth inhibition at 500 and 1000 nM when compared to the control at 24 h. G0/G1 analysis showed a statistically significant difference between 100 and 500 nM (P<0.005), 100 and 1000 nM (P<0.001), 300 and 1000 nM (P<0.001), and 500 and 1000 nM (P<0.001). Flavopiridol also significantly influenced the cells in the G2/M phase, particularly at high-dose treatments. Flavopiridol induced growth inhibition and apoptosis at the IC50 dose (500 nM), resulting in a significant increase in immunofluorescence staining of caspase-3, caspase-8 and p53. In conclusion, the present results indicated that flavopiridol could be a useful therapeutic agent for prostate CSCs by inhibiting tumor growth and malignant progression, and inducing apoptosis.

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“…Acute myeloid leukemia (AML) is a complex clonal malignancy that is defined by immature myeloid cell proliferation and BM failure [35]. The incidence of AML in the United States is 3.5 cases per 100,000 and it is higher in patients over 65 years old [36]. In 2008, WHO classified seven AML subtypes: 1-AML with recurrent genetic abnormalities and with gene mutations; 2-AML with myelodysplasia-related changes; 3-therapy-related myeloid neoplasms; 4-AML not otherwise specified (NOS); 5-myeloid sarcoma; 6-myeloid proliferations related to the Down syndrome; and, 7-blastic plasmacytoid dendritic cell neoplasms [37].…”

Section: Mir-144 In Acute Myeloid Leukemiamentioning

confidence: 99%

MiR-144: A New Possible Therapeutic Target and Diagnostic/Prognostic Tool in Cancers

Kooshkaki

Rezaei

Rahmati

et al. 2020

IJMS

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MicroRNAs (miRNAs) are small and non-coding RNAs that display aberrant expression in the tissue and plasma of cancer patients when tested in comparison to healthy individuals. In past decades, research data proposed that miRNAs could be diagnostic and prognostic biomarkers in cancer patients. It has been confirmed that miRNAs can act either as oncogenes by silencing tumor inhibitors or as tumor suppressors by targeting oncoproteins. MiR-144s are located in the chromosomal region 17q11.2, which is subject to significant damage in many types of cancers. In this review, we assess the involvement of miR-144s in several cancer types by illustrating the possible target genes that are related to each cancer, and we also briefly describe the clinical applications of miR-144s as a diagnostic and prognostic tool in cancers.Int. J. Mol. Sci. 2020, 21, 2578 2 of 23 of a mRNA molecule [3]. MiRNAs indicate a new perspective in the study of cancers. More than 50% of miRNA genes were discovered to be located within the genomic regions that are involved in cancers, suggesting their role in human cancer pathogenesis. In pathological conditions, MiRNAs can negatively regulate gene expression and they are associated with tumor growth, apoptosis, invasion, and metastasis. In the past, several studies have indicated the ability of miRNAs in the inhibition of tumors as a critical option for the improvement of cancer therapy [4,5]. Tumor activator miRNAs, called oncomiRs, are overexpressed in various cancers. On the contrary, suppressive tumor miRNAs are underexpressed [6][7][8]. Among several miRNAs assessed, miR-144s seem to have a role in several cancers. These miRNAs are located in the chromosomal region 17q11.2, being significantly destroyed in many types of cancers. The predicted stem-loop structure of miR-144s recognized by the miRBase (http://mirbase.org/) is shown in Figure 1A. The miR-144 hairpin gives rise to the "guide strand" miR-144-5p and the sister "passenger" strand miR-144-3p ( Figure 1B).

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Acute Myeloid Leukaemia

Cited by 21 publications

References 109 publications

A Novel Subset of Anti-Inflammatory CD138+ Macrophages Is Deficient in Mice with Experimental Lupus

A Novel Subset of Anti-Inflammatory CD138+ Macrophages Is Deficient in Mice with Experimental Lupus

Induced growth inhibition, cell cycle arrest and apoptosis in CD133+/CD44+ prostate cancer stem cells by flavopiridol

MiR-144: A New Possible Therapeutic Target and Diagnostic/Prognostic Tool in Cancers

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