Cyclooxygenase‐1, but not ‐2, in blast cells of patients with acute leukemia

Truffinet, Véronique; Donnard, Magali; Vincent, Christelle; Faucher, Jean‐Luc; Bron, Dominique; Turlure, Pascal; Trimoreau, Franck; Denizot, Yves

doi:10.1002/ijc.22786

Cited by 15 publications

(13 citation statements)

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“…The growth-promoting properties of COX-2 in physiological responses are diverted in malignancies [10]. COX-1 and COX-2 transcripts are documented in AML and ALL blasts [11], but only the COX-1 protein is found. Similarly COX-1, but not the COX-2 protein, is detected in human primary promyelocytic blasts during differentiation [12].…”

Section: Cox and Human Leukemic Blastsmentioning

confidence: 99%

“…Data reporting the ability of PGE 2 to modulate several functions in mature blood cells such as monocyte-macrophages, dendritic cells, and T and B lymphocytes can be readily found. Human AML and ALL blasts spontaneously release PGE 2 [11], with PGE 2 synthesis being inhibited by indomethacin. Transcripts for mPGES-1 are detected in AML and ALL blasts suggesting its role in PGE 2 synthesis (Denizot and coll., unpublished results).…”

Section: Pge2 Ep Receptors and Human Leukemic Blastsmentioning

confidence: 99%

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Lipid Mediators and Human Leukemic Blasts

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Vincent-Fabert

Guérin

et al. 2011

Journal of Oncology

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Some of the most potent inflammatory mediators share a lipid origin. They regulate a wide spectrum of cellular processes including cell proliferation and apoptosis. However, the precise roles and ways (if any) in which these compounds impact the growth and apoptosis of leukemic blasts remain incompletely resolved. In spite of this, significant advances have been recently made. Here we briefly review the current knowledge about the production of lipid mediators (prostaglandins, leukotrienes, platelet-activating factor) by leukemic blasts, the enzymatic activities (phospholipase A2, cyclooxygenases, lipoxygenases) involved in their productions and their effects (through specific membrane bound receptors) on the growth, and apoptosis of leukemic blasts.

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Section: Cox and Human Leukemic Blastsmentioning

confidence: 99%

Section: Pge2 Ep Receptors and Human Leukemic Blastsmentioning

confidence: 99%

Lipid Mediators and Human Leukemic Blasts

Fiancette

Vincent-Fabert

Guérin

et al. 2011

Journal of Oncology

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“…1,2 The COX and lipoxygenase pathways of AA have been recently documented on immature leukemic blasts of patients with acute myeloid (AML) and acute lymphoid (ALL) leukemia. 4,5 Thus, freshly isolated AML and ALL blasts express COX-1, produce the AA metabolite prostaglandin E 2 , express functional EP 2 receptors and increase their growth in response to exogenously added prostaglandin E 2 . The World Health Organization has proposed a classification system that divides AML into several broad groups: AML with genetic abnormalities, AML with multilineage dysplasia, AML related to earlier chemotherapy or radiation and AML not otherwise specified.…”

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confidence: 99%

“…It is interesting that prostaglandin E 2 , a COX metabolite of AA, was recently reported to stimulate the growth of leukemic blasts through an EP 2 receptor-dependent pathway. 4 These results show that mRNA from four out of five cytosolic PLA 2 (PLA 2 -IVA, PLA 2 -IVB, PLA 2 -IVC and PLA 2 -VI) and six out of nine sPLA 2 (PLA 2 -IB, PLA 2 -IIA, PLA 2 -IID, PLA 2 -V, PLA 2 -X and PLA 2 -XII) are present in leukemic blasts, and that their mRNA transcript levels exhibited important variations as compared with blood mononuclear cells (summarized in Table 1). One of the more notable finding is that leukemic blasts expressed high amounts of PLA 2 -VI and PLA 2 -X.…”

mentioning

confidence: 99%

“…RQ-PCR was performed according to a standard protocol at the Adult Leukaemia Unit, Hammersmith Hospital. 4 At trial entry, patients received IM according to their established dose level (400 mg for all patients). After informed consent was obtained, patients were randomized to receive either Lenograstim (rHu-G-CSF, 263 mg, provided by Chugai Pharma UK and France) on days 24, 26 and 28 of each cycle in combination with pIM (pIM-G) therapy, pIM therapy alone or continuous IM (cIM) therapy alone (IM given at earlier dose level).…”

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Genes encoding multiple forms of phospholipase A2 are expressed in immature forms of human leukemic blasts

et al. 2009

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In conclusion, IM dose escalation represents a valuable option leading, in a vast majority of patients, to optimal cytogenetic and molecular responses in patients with suboptimal cytogenetic responses to frontline IM 400. In patients with primary suboptimal molecular responses, this strategy seems to be less effective and the potential of second-generation tyrosine kinase inhibitors or combination strategies should be investigated to prevent overt resistance.

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mPGES-1 in leukemic cells of AML patients

et al. 2012

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We read with a great interest the article by Li et al. [1] demonstrating the mechanism leading to MK886-induced apoptosis in HL-60 cells [a human acute myelogenous leukemia (AML) cell line] by downregulation of microsomal prostaglandin E synthase-1 (mPGES-1) and, thus, reduced prostaglandin E 2 (PGE 2 ) synthesis. Authors indicate that their study reveals, for the first time, that mPGES-1 is overexpressed in HL-60 cells as compared with control blood mononuclear cells and that mPGES-1 inhibitors should be considered as promising candidate for leukemia treatment. We think that the results obtained with leukemic cell lines may be different from those obtained from freshly isolated leukemic cells. Phospholipase A 2 (PLA 2 ), cyclooxygenases (COX-1 and COX-2) and mPGES-1 are the key enzymes that control PGE 2 synthesis [2, 3]. We have previously reported PLA 2 enzymatic activities [4, 5] [6]. We have investigated mPGES-1 transcripts in leukemic cells from AML patients to confirm whether mPGES-1 is expressed more highly than in control blood mononuclear cells. Real time PCR analysis reveals that mPGES-1 mRNAs are detected in 100% (24/24) of leukemic cells from AML patients and 100% (7/7) of control blood mononuclear cells (Fig. 1). However, no significant differences (P = 0.5, Mann-Whitney U test) were found between mPGES-1 transcript levels in AML patients (relative expression of 36.7 ± 7.9; mean ± SEM in 24 patients) and control blood mononuclear cells (relative expression 37.4 ± 10.5; mean ± SEM in seven donors). In conclusion, data obtained using HL-60 cells are different from those obtained using freshly isolated blood mononuclear cells. The current results do not support the hypothesis that mPGES-1 inhibitor should be considered as a promising candidate for leukemia treatment.Acknowledgments This work was supported in part by a grant from «La ligue Contre le Cancer, Comité de la Corrèze et de la HauteVienne».

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Cyclooxygenase‐1, but not ‐2, in blast cells of patients with acute leukemia

Cited by 15 publications

References 12 publications

Lipid Mediators and Human Leukemic Blasts

Lipid Mediators and Human Leukemic Blasts

Genes encoding multiple forms of phospholipase A2 are expressed in immature forms of human leukemic blasts

mPGES-1 in leukemic cells of AML patients

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