Partial myeloperoxidase deficiency in preleukemia

Čech, Petr; Markert, Michèle; Perrin, Luc

doi:10.1007/bf00321047

Cited by 15 publications

(4 citation statements)

References 26 publications

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“…Case reports have linked MPO deficiency with a variety of clinical disorders, including dermatologic syndromes with or without associated defects in neutrophil chemotaxis [111, 120 -122] and disseminated candidiasis in the setting of preeclampsia [123] or pre-maturity [124], although the causal link with MPO deficiency is lacking. MPO deficiency has also been associated with clinical settings unrelated to host defense against infection, with reports of increased susceptibility to malignant diseases [125][126][127][128][129][130][131][132][133] and decreased susceptibility to neutrophil-mediated vascular dysfunction [118].…”

Section: Mpo-deficient Neutrophilsmentioning

confidence: 99%

Myeloperoxidase: a front-line defender against phagocytosed microorganisms

Klebanoff

Kettle

Rosen

et al. 2013

Journal of Leukocyte Biology

582

465

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Successful immune defense requires integration of multiple effector systems to match the diverse virulence properties that members of the microbial world might express as they initiate and promote infection. Human neutrophils--the first cellular responders to invading microbes--exert most of their antimicrobial activity in phagosomes, specialized membrane-bound intracellular compartments formed by ingestion of microorganisms. The toxins generated de novo by the phagocyte NADPH oxidase and delivered by fusion of neutrophil granules with nascent phagosomes create conditions that kill and degrade ingested microbes. Antimicrobial activity reflects multiple and complex synergies among the phagosomal contents, and optimal action relies on oxidants generated in the presence of MPO. The absence of life-threatening infectious complications in individuals with MPO deficiency is frequently offered as evidence that the MPO oxidant system is ancillary rather than essential for neutrophil-mediated antimicrobial activity. However, that argument fails to consider observations from humans and KO mice that demonstrate that microbial killing by MPO-deficient cells is less efficient than that of normal neutrophils. We present evidence in support of MPO as a major arm of oxidative killing by neutrophils and propose that the essential contribution of MPO to normal innate host defense is manifest only when exposure to pathogens overwhelms the capacity of other host defense mechanisms.

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Section: Mpo-deficient Neutrophilsmentioning

confidence: 99%

Myeloperoxidase: a front-line defender against phagocytosed microorganisms

Klebanoff

Kettle

Rosen

et al. 2013

Journal of Leukocyte Biology

582

465

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“…Studies are also currently underway to characterize genomic DNA and MPO gene expression in cells from patients with the acquired MPO deficiency seen in some patients with acute promyelocytic leukemia. Estimates of the size of this population vary, although some studies indicate prevalences as high as 48% for AML (92), 20% CML (26), and 57% for M2-4 leukemias (93). In addition, some patients with preleukemia (93) and myelodysplasia (94,95) have been reported to have acquired MPO deficiency.…”

Section: The Gene For Mpomentioning

confidence: 99%

“…Estimates of the size of this population vary, although some studies indicate prevalences as high as 48% for AML (92), 20% CML (26), and 57% for M2-4 leukemias (93). In addition, some patients with preleukemia (93) and myelodysplasia (94,95) have been reported to have acquired MPO deficiency. Certainly these patients represent obvious examples of clinically relevant situations in which to examine the relationship between MPO gene expression and myeloid differentiation.…”

Section: The Gene For Mpomentioning

confidence: 99%

Biosynthesis and processing of myeloperoxidase — A marker for myeloid cell differentiation

Nauseef

Olsson

Arnljots

1988

European J of Haematology

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Myeloperoxidase (MPO), a heme protein, is a major component of azurophilic granules of neutrophils. Optimal oxygen-dependent microbicidal activity depends on MPO as the critical enzyme for the generation of hypochlorous acid and other toxic oxygen products. MPO is synthesized during the promyelocytic stage of myeloid differentiation, the stage at which azurophilic granules are formed. Like other lysoso-ma1 enzymes, MPO is synthesized as a larger precursor which is subsequently processed and transported intracellularly to the lysosomes. The primary translation product is a single SO-kDa protein which undergoes cotranslational N-linked glycosylation to produce a 92-kDa glycoprotein. Glucosidases in the endoplasmic reticulum or early cis Golgi convert the proMPO to a 90-kDa form which is sorted into a prelysosomal compartment that undergoes final proteolytic maturation to native MPO, a pair of heavy-light protomers with subunits of 60 kDa and a 12 kDa. These events contrast with similar processes seen with other lysosomal enzymes in two ways. First, alkalinization of lysosomes with NH,+ does not alter processing or transport, in contrast to the pH dependence of these processes for other lysosomal enzymes. However, some studies indicate retardation of processing in the presence of the proton ionophore monensin. Second, intracellular transport of MPO is not apparently mediated by the mannose-6-phosphate receptor system. The gene for MPO is on the long arm of chromosome 17 (17q22, 23) near the breakpoint of the 15, 17 translocation of acute promyelocytic leukemia. The gene spans approximately 14 kb and contains 11 introns and 12 exons. The cloned full-length cDNA is approximately 2.2 kb and both normal bone marrow and cultured promyelocytic leukemia cells express two species of mRNA. Inherited MPO deficiency, a relatively common disorder, is associated with the absence of mature MPO but the presence of proMPO, consistent with a posttranslational defect. Studies at the molecular level aimed at identifying the underlying genetic defect are thus far consistent with that hypothesis. In addition, the basis for the observed association between acquired MPO deficiency and some myeloid leukemias can now be studied at the molecular level using these probes.

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“…Infectious and inflammatory diseases have also been observed in approximately 50% of human patients evaluated (9). Hematologic neoplasms were a further differential diagnose in human patients with MPOD (2,4). In the current study, just one patient suffered from lymphoma.…”

Section: Discussionmentioning

confidence: 54%

Myeloperoxidase deficiency in dogs observed with the ADVIA®120

Klenner¹,

Richartz²,

Bauer³

et al. 2010

Tierarztl Prax Ausg K

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Objective:In contrast to humans, neutrophil myeloperoxidase deficiency (MPOD) has been rarely investigated in dogs. The hematology analyzer ADVIA ® 120 differentiates leukocytes based on the cellular volume and their myeloperoxidase concentration. The aim of this study was the characterization of myeloperoxidase deficiency in dogs and the evaluation of the diagnostic use of the ADVIA ® 120 Myeloperoxidase Index (MPXI). Material and methods: ADVIA ® peroxidase scatter plots indicative of MPOD were reviewed. Severity of MPOD was classified semiquantitatively in three groups (MPOD grade 1-3): MPOD grade 1 (MPOD-1): neutrophils showing an abnormal shift of the population, < 25% extending in the monocyte cluster and therefore misclassified, MPOD-2: ∼25-50% of neutrophils misclassified, MPOD-3: 50-100% of the neutrophils misclassified due to their location in the monocyte cluster. Sex, age, and breed of the dogs as well as diagnosis, and MPXI were recorded. Results: 29 dogs (nine females and 20 males belonging to 23 breeds) with 38 analyses consistent with MPOD were found. Diseases were characterized by severe leukocyte consumption and included mainly parvovirosis (8/29), DIC/sepsis (3/29), pyometra, pyothorax, pneumonia, pancreatic abscess, and cystitis. A significantly lower mean MPXI in MPOD-3 was present in comparison to the mean MPXI of MPOD-1 (p < 0.05), however, there was a great overlap between the groups. Conclusion: Diseases associated with neutrophil consumption may show an acquired MPOD in dogs. High standard deviation limits the diagnostic use of the MPXI for detection of MPOD. Clinical relevance: The ADVIA ® 120 cytograms are a good screening tool for detection of MPOD in dogs, but the use of the MPXI is impaired in this species. ZusammenfassungGegenstand und Ziel: Ein Myeloperoxidasemangel (myeloperoxidase deficiency, MPOD) neutrophiler Granulozyten wurde beim Hund im Gegensatz zum Menschen nur selten untersucht. Das Hämatologiegerät ADVIA ® 120 differenziert Leukozyten anhand ihrer Größe sowie des intrazellulären MPO-Gehalts. Ziel der Studie war die Beschreibung von Hunden mit MPOD sowie die Evaluierung des ADVIA ® -spezifischen Mye loperoxidaseindexes (MPXI) zur Diagnostik des MPOD bei Hunden. Material und Methoden: Retrospektiv wurden mit dem ADVIA ® 120 erstellte und für MPOD verdächtige Peroxidase-Scattergramme ausgewertet und der Schweregrad des MPOD semiquantitativ in drei Kategorien eingeteilt: MPOD-1: Die neutrophilen Granulozyten zeigten eine anormale Lage im Neutrophilencluster, < 25% wurden aufgrund ihrer Lage im Monozytencluster als Monozyten missklassifiziert; MPOD-2: Missklassifikation von ca. 25-50% der neutrophilen Granulozyten; MPOD-3: 50-100% der neutrophilen Granulozyten lagen fälschlicherweise im Monozytencluster. Geschlecht, Alter und Diagnose der Patienten sowie deren MPXI wurden erfasst. Ergebnisse: Bei 29 Hunden (9 Hündinnen, 20 Rüden 23 unterschiedlicher Rassen) mit 38 Analysen ergab sich eine MPOD. Die Erkrankungen waren durch hohen Leukozytenverbrauch charakterisiert, wobei vo...

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Partial myeloperoxidase deficiency in preleukemia

Cited by 15 publications

References 26 publications

Myeloperoxidase: a front-line defender against phagocytosed microorganisms

Myeloperoxidase: a front-line defender against phagocytosed microorganisms

Biosynthesis and processing of myeloperoxidase — A marker for myeloid cell differentiation

Myeloperoxidase deficiency in dogs observed with the ADVIA®120

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