Search results for "Myeloid"

TLRs control hematopoiesis during infection

2013

Recent research has shown that (i) Toll-like receptor (TLR) agonists drive hematopoietic stem and progenitor cells (HSPCs) to proliferate and differentiate along the myeloid lineage in vitro, and (ii) direct TLR-mediated stimulation of HSPCs also promotes macrophage differentiation in vivo following infection. These new insights demonstrate that TLR signaling in HSPCs, in addition to other TLR-dependent mechanisms, can contribute to HSPC expansion and myeloid differentiation after infection. Evidence is, therefore, mounting that direct TLR-induced programming of hematopoiesis plays a key role in host defense by rapidly replenishing the innate immune system with the cells needed to deal with…

Natural Inhibitors of P-glycoprotein in AcuteMyeloid Leukemia

2023

Acute myeloid leukemia (AML) remains an insidious neoplasm due to the percentage of patients who develop resistance to both classic chemotherapy and emerging drugs. Multidrug resistance (MDR) is a complex process determined by multiple mechanisms, and it is often caused by the overexpression of efflux pumps, the most important of which is P-glycoprotein (P-gp). This mini-review aims to examine the advantages of using natural substances as P-gp inhibitors, focusing on four molecules: phytol, curcumin, lupeol, and heptacosane, and their mechanism of action in AML.

Chemotherapy with Idarubicin, Ara-C,VP-16, Amsacrine, Followed by G-CSF and Maintenance Immunotherapy with Interleukin-2 for Patients with High-Risk …

1998

To improve the complete remission (CR) rate and to prolong CR duration in patients with advanced MDS, AML evolving from MDS, and secondary AML, a phase-III trial of aggressive chemotherapy followed by G-CSF was initiated in January 1992. Pts. achieving a CR were randomized to receive either high-dose or low-dose IL-2 to evaluate the potential of this cytokine to eliminate residual leukemic cells and to prolong the CR duration.

Langerinneg conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice.

2013

Psoriasis is an autoinflammatory skin disease of unknown etiology. Topical application of Aldara cream containing the Toll-like receptor (TLR)7 agonist Imiquimod (IMQ) onto patients induces flares of psoriasis. Likewise, in mice IMQ triggers pathological changes closely resembling psoriatic plaque formation. Key cytokines like IL-23 and type-I IFN (IFN-I), both being produced mainly by dendritic cells (DCs), have been implicated in psoriasis. Although plasmacytoid DCs (pDCs) are the main source of IFNα and thought to initiate disease, conventional DCs (cDCs) appear to maintain the psoriatic lesions. Any role of cDCs during lesion formation remains elusive. Here, we report that selective ac…

Exclusive Expression of MyD88 on Dendritic Cells Is Sufficient to Induce Protection against Experimental Leishmaniasis

2022

Novel insights on [1,2]oxazolo[5,4‐e]isoindoles on multidrug resistant acute myeloid leukemia cell line

2022

A series of [1,2]oxazolo[5,4‐e]isoindole derivatives was evaluated against HL‐60 cell line and its multidrug resistance (MDR) variant, HL‐60R, resistant to doxorubicin and to other P‐gp substrates by overexpressing the efflux pump. They displayed antiproliferative activities, with IC50 values ranging from 0.02 to 5.5μM. In particular, the newly synthesized compound 4k produced synergistic effects in terms of cell growth inhibition and cell death induction either in combination with a Vinca alkaloid, Vinblastine, and a Taxane, Paclitaxel in HL‐60R cells. The study of the mechanism of action indicated that all compounds showed antimitotic activity through inhibition of tubulin polymerization.…

Leukemia Cutis: A Report of 17 Cases and a Review of the Literature

2016

Dermatologic manifestations of leukemia can be both specific and nonspecific (e.g., opportunistic infections, purpura and ecchymosis, Sweet syndrome). Leukemia cutis refers to the infiltration of the skin with neoplastic leukocytes and its early diagnosis has important prognostic implications. We report on 17 cases of leukemia cutis seen in our department between 1994 and 2014 and describe the characteristics of the patients (age, sex, medical history), the morphology of the lesions, and associations with systemic disease. Most of the patients were male and the most common associated malignancy was acute myeloid leukemia. The most frequent dermatologic manifestations were nodules or erythem…

Role of the protein phosphatase CD45 and lipid rafts in the maintenance of acute myeloblastic leukemiaand development of a new therapeutic treatment

2017

CD45 is a pan-leukocyte protein with tyrosine phosphatase activity involved in the regulation of cytokinereceptors in hematopoiesis, such as the GM-CSF. We report here on new chemical compound,Pyrido[4,3-b]quinoxaline (PyQ), which is a plasma membrane disrupting agent, as a potential drug fortreatment of acute myeloid leukemia (AML). Indeed, we show that the hematopoietic cell lines aremore sensitive to PyQ, compared with non- hematopoietic cell lines. Using HOXA9-MEIS1-transformed blasts from a mouse model to study AML and human primary AML samples, wediscovered that CD45, which is mainly found within plasma-membrane lipid rafts, is rapidly delocalizedafter treatment with PyQ compound. The…

Mitophagy in myeloid cells : role in infection with gram-negative bacteria

2017

Sepsis and related organ dysfunctions remain a leading cause of mortality in intensive care units. Increasing evidences have shed light on an unexpected link between mitochondria and immune cell functions. Alterations in mitochondrial functions have been reported in peripheral blood cells in sepsis. We hypothesize here that mitophagy might impact on phagocyte functions in the context of bacterial infection. Mitophagy is a mitochondria-dedicated autophagy that governs the elimination of dysfunctional mitochondria. We demonstrated here in vivo and in vitro that macrophages exposed to Gram-negative bacteria or their cell wall component LPS display a marked inhibition of mitophagy that constitu…

Release of IL-12 by dendritic cells activated by TLR ligation is dependent on MyD88 signaling, whereas TRIF signaling is indispensable for TLR synerg…

2010

Abstract Synergistic activation of dendritic cells by combinations of TLR ligands requires both MyD88- and TRIF-dependent signaling. Recently, it has been shown that certain combinations of TLR ligands act in synergy to induce the release of IL-12 by DCs. In this study, we sought to define the critical parameters underlying TLR synergy. Our data show that TLR ligands act synergistically if MyD88- and TRIF-dependent ligands are combined. TLR4 uses both of these adaptor molecules, thus activation via TLR4 proved to be a synergistic event on its own. TLR synergy did not affect all aspects of DC activation but enhanced primarily the release of certain cytokines, particularly IL-12, whereas the …