The ADVIA 2120 Hematology System: Flow Cytometry-Based Analysis of Blood and Body Fluids in the Routine Hematology Laboratory

Harris, Neil; Kunicka, Jolanta E.; Kratz, Alexander

doi:10.1532/lh96.04075

Cited by 113 publications

(100 citation statements)

References 39 publications

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“…13 Neutrophil granulocytes are identified by the presence of dark precipitates within the cells that are generated by the conversion of H 2 O 2 and 4-chloro-1-naphthol by intracellular MPO. Neutrophil granulocytes devoid of MPO activity lack precipitates and appear as large unstained cells (LUC) ( Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

Homozygous calreticulin mutations in patients with myelofibrosis lead to acquired myeloperoxidase deficiency

Theocharides

Lundberg

Lakkaraju

et al. 2016

Blood

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Key Points• Acquired MPO deficiency in patients with MPN is uniquely associated with homozygous CALR mutations.• In line with a posttranscriptional defect, MPO deficiency results from reduced MPO protein levels, but not from decreased MPO mRNA.The pathogenesis of acquired myeloperoxidase (MPO) deficiency, a rare phenomenon observed in patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), is unknown. MPO is a glycoprotein (GP) chaperoned by calreticulin (CALR) in the endoplasmic reticulum. Mutations in CALR are frequently found in patients with myelofibrosis (MF) and essential thrombocythemia (ET) with nonmutated Janus kinase 2 (JAK2). We hypothesized that acquired MPO deficiency in MPN could be associated with the presence of CALR mutations. A cohort of 317 patients with MPN (142 polycythemia vera [PV], 94 ET, and 81 MF) was screened for MPO deficiency. MPO deficiency was observed in 6/81 MF patients (7.4%), but not in PV or ET patients. Susceptibility to infections had been documented in 2/6 (33%) MPO-deficient patients. Five out of 6 patients with MPO deficiency carried a homozygous CALR mutation and were also deficient in eosinophilic peroxidase (EPX). In contrast, 1 patient with MF, a JAK2-V617F mutation, and MPO deficiency, carried 2 previously reported MPO mutations and showed normal EPX activity. Patients with homozygous CALR mutations had reduced MPO protein, but normal MPO messenger RNA (mRNA) levels supporting a posttranscriptional defect in MPO production. Finally, we demonstrate in vitro that in the absence of CALR, immature MPO protein precursors are degraded in the proteasome. Therefore, 4 decades after the first description of acquired MPO deficiency in MPN, we provide the molecular correlate associated with this phenomenon and evidence that CALR mutations can affect the biosynthesis of GPs. (Blood. 2016;127(25):3253-3259)

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Section: Resultsmentioning

confidence: 99%

Homozygous calreticulin mutations in patients with myelofibrosis lead to acquired myeloperoxidase deficiency

Theocharides

Lundberg

Lakkaraju

et al. 2016

Blood

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“…First, after lysis of red blood cells (RBCs), the tungsten-halogen based optical system of the MPO channel measures cell size by forward light scatter, and stain intensity by absorbance, thereby counting and differentiating granulocytes, lymphocytes, and monocytes based on their size and MPO content. Second, the laser diode-based optical system of the lobularity/nuclear density channel counts and classifies cells according to size, lobularity, and nuclear density [17,18]. The formula for calculating DNI is as follows: DNI = [the neutrophil subfraction and the eosinophil subfraction measured in the MPO channel by cytochemical MPO reaction] -[the PMN subfraction measured in the nuclear lobularity channel by the reflected light beam].…”

Section: Dni and Other Blood Sample Measurementsmentioning

confidence: 99%

“…Recent technological advances have led to specific modern automated cell analyzers that can provide information on leukocyte differentials based on cytochemical myeloperoxidase (MPO) reaction and nuclear lobularity of the white blood cells [15][16][17]. Delta neutrophil index (DNI), the difference between the leukocyte differentials measured in the MPO channel and those assayed in the nuclear lobularity channel, reflects the fraction of circulating immature granulocytes.…”

Section: Introductionmentioning

confidence: 99%

Delta Neutrophil Index as a Prognostic Marker in the Pediatric Intensive Care Unit

Sol

Park

Kim

et al. 2016

Korean J Crit Care Med

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“…Mean platelet volumes were measured separately on 150 L of whole blood obtained by retro-orbital puncture and diluted with 150 L 1.25% bovine serum albumin (BSA) in phosphate-buffered saline (PBS) on the Advia 2120 (Bayer Diagnostics, Tarrytown, NY), which optimized measurement of platelet volume. [23][24][25] Platelet half-life studies Platelets were isolated from animals that were either wild-type (WT) for PF4 or overexpressed hPF4. Briefly, animals were anesthetized, blood was isolated from the portal vein, and 600 L of blood was placed in acid-citrate-dextrose (ACD) buffer and centrifuged at 200g for 10 minutes at room temperature to prepare platelet-rich plasma (PRP).…”

Section: Platelet Counting and Sizementioning

confidence: 99%

Platelet factor 4 is a negative autocrine in vivo regulator of megakaryopoiesis: clinical and therapeutic implications

Lambert

Rauova

Bailey

et al. 2007

Blood

109

115

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Platelet factor 4 (PF4) is a negative regulator of megakaryopoiesis in vitro. We have now examined whether PF4 regulates megakaryopoiesis in vivo by studying PF4 knockout mice and transgenic mice that overexpress human (h) PF4. Steady-state platelet count and thrombocrit in these animals was inversely related to platelet PF4 content. Growth of megakaryocyte colonies was also inversely related to platelet PF4 content. Function-blocking anti-PF4 antibody reversed this inhibition of megakaryocyte colony growth, indicating the importance of local PF4 released from developing megakaryocytes. The effect of megakaryocyte damage and release of PF4 on 5-fluorouracil-induced marrow failure was then examined. Severity of thrombocytopenia and time to recovery of platelet counts were inversely related to initial PF4 content. Recovery was faster and more extensive, especially in PF4-overexpressing mice, after treatment with anti-PF4 blocking antibodies, suggesting a means to limit the duration of such a chemotherapy-induced thrombocytopenia, especially in individuals with high endogenous levels of PF4. We found that approximately 8% of 250 healthy adults have elevated (> 2 times average) platelet PF4 content. These individuals with high levels of platelet PF4 may be especially sensitive to developing thrombocytopenia after bone marrow injury and may benefit from approaches that block the effects of released PF4. IntroductionMegakaryopoiesis is a complex process that is still not fully understood. Early studies identified thrombopoietin (TPO) as the predominant cytokine responsible for regulating platelet counts. However, many other cytokines have been postulated to participate in regulating megakaryopoiesis by increasing TPO expression in the liver (eg,), enhancing megakaryocyte chemotaxis (eg, stromal-derived factor-1 [SDF-1]), 1 or directly stimulating megakaryocyte development (eg, IL-11). 2 A pathway by which megakaryopoiesis is auto-down-regulated has been suggested based on in vitro studies of platelet factor 4 (PF4) and later by studies of other chemokines that are also stored in ␣-granules, including the related CXC chemokines, neutrophil activating peptide-2 (NAP-2), and 3,4 and the more distantly related CC chemokines, RANTES (regulated upon activation, normal T-cell-expressed and secreted), 5 and MIP-1␣ (macrophage inflammatory peptide-1␣). 4,5 PF4 is a 7.8-kDa protein that is produced primarily in megakaryocytes and expressed in platelets as a tetramer, where it comprises a significant portion of the content of ␣-granules (2.5% on a molar basis). 6 The biological role of PF4 is not fully understood. Unlike other chemokines that have clearly defined chemokine receptors, PF4 appears to function by binding with high affinity to glycosaminoglycans on cell surfaces. 7-9 PF4 has been proposed to participate in many important biological process based primarily on in vitro studies, including roles in angiogenesis, 10 inflammation, 11 atherosclerosis, 12,13 thrombosis, [14][15][16][17] and megakaryopoiesis. 4,5,18 Studies...

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The ADVIA 2120 Hematology System: Flow Cytometry-Based Analysis of Blood and Body Fluids in the Routine Hematology Laboratory

Cited by 113 publications

References 39 publications

Homozygous calreticulin mutations in patients with myelofibrosis lead to acquired myeloperoxidase deficiency

Homozygous calreticulin mutations in patients with myelofibrosis lead to acquired myeloperoxidase deficiency

Delta Neutrophil Index as a Prognostic Marker in the Pediatric Intensive Care Unit

Platelet factor 4 is a negative autocrine in vivo regulator of megakaryopoiesis: clinical and therapeutic implications

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