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Identification of target genes using gene expression profile of granulocytes from patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors.

Differential gene expression analysis by suppression subtractive hybridization with correlation to the metabolic pathways involved in chronic myeloid leukemia (CML) may provide a new insight into the pathogenesis of CML. Among the overexpressed genes found in CML at diagnosis are SEPT5, RUNX1, MIER1, KPNA6 and FLT3, while PAN3, TOB1 and ITCH were decreased when compared to healthy volunteers. Some genes were identified and involved in CML for the first time, including TOB1, which showed a low expression in patients with CML during tyrosine kinase inhibitor treatment with no complete cytogeneti

BCR-ABL1 transcript levels increase in peripheral blood but not in granulocytes after physical exercise in patients with chronic myeloid leukemia.

In chronic myeloid leukemia (CML) treatment response is determined by measurements of BCR-AB1L transcripts in peripheral blood by quantitati … after exercise. A biphasic increase in leukocyte count was observed and the relative proportion of granulocytes in peripheral blood changed significantly after exercise compared with baseline (p < 0.001). The BCR-ABL1 transcript level increased significantly following exercise, in nucleated cell fraction of peripheral blood (p < 0.05) but not in isolated gran …

Expression of CD4 on peripheral blood granulocytes. a novel finding in a case of myelodysplastic syndrome in association with t(5;12).

Myelodysplastic syndromes (MDS) are associated with cell maturation defects that can manifest as abnormal surface antigen expression. We describe a patient with refractory anemia with excess blasts, who presented with infection and extensive dysplastic features in peripheral blood granulocytes. The granulocytes expressed CD11b, CD13, CD15, CD33, and CD43. The granulocytes also expressed CD4 antigen. Cytogenetic analysis showed a clonal t(5;12)(q33;p13). The patient improved on antibiotics with partial improvement in the dysplastic features. However, shortly after, the patient experienced parav…

Sequential study of myeloid differentiation antigens of neutrophil granulocytes in different phases of chronic myeloid leukaemia: natural history and prognostic significance.

In an attempt to contribute to the knowledge of the natural history of Philadelphia-chromosome-positive chronic myeloid leukaemia (CML) and its prognosis, we analyzed sequentially the myeloid differentiation antigens of peripheral blood neutrophil granulocytes (NG) in different evolutive stages of the disease. Four monoclonal antibodies (CD15, CD24, 31D8, and 13F6) were used, and a total number of 116 sequential studies were performed in 43 patients. At diagnosis, there is a significant decrease of NG expressing myeloid differentiation antigens, which recover to nearly normal levels after init…

Evolution of mixed chimerism after allogeneic bone marrow transplantation as determined on granulocytes and mononuclear cells by the polymerase chain reaction.

To evaluate the clinical relevance of mixed chimerism (MC) after allogeneic bone marrow transplantation (BMT), we developed a method based on amplification of DNA minisatellites by the polymerase chain reaction (PCR). This sensitive method by which MC lower than 1% can be detected is applicable to any patient-donor pair. Furthermore, because the analysis requires only small amounts of DNA, it allowed us to analyze samples early after BMT and during graft rejection. Results were obtained within 48 hours after blood sampling. Determination of MC in granulocytes (GR) and in mononuclear cells (Mnc…

[The functional characteristics of the interaction of lymphokine-producing lymphocytes with granulocytes of the peripheral blood and skin in dermatosis patients].

PHA-induced mononuclear production of lymphokines altering leukocyte migration was studied in patients with psoriasis, mycosis, and scabies. The findings evidence that T-cells synthesize leukocyte migration inhibition factor (LMIF) in mycosis and scabies, whereas in psoriasis they produce both LMIF and leukocyte migration stimulation factor (LMSF). Blood leukocytes of mycosis and scabies patients were more sensitive to LMIF than the cells of psoriasis patients. The 'skin fenestra' cells (granulocytes) of these patients were functionally active only in respect of LMIF, even when mononuclears sy…

Serum-dependent interaction of granulocytes with Onchocerca volvulus microfilariae in generalized and chronic hyper-reactive onchocerciasis and its modulation by diethylcarbamazine.

The adherence and cytotoxicity of granulocytes to microfilariae of Onchocerca volvulus were examined in vitro. Reactivity and modulation by diethylcarbamazine of isolated eosinophilic and neutrophilic granulocytes from patients with generalized and chronic hyper-reactive onchocerciasis (sowda or localized form) from endemic foci in Liberia were evaluated under varying serum conditions. In the presence of pooled sera from patients with generalized onchocerciasis granulocytes from both polar groups of patients exhibited similar adherence rates, whereas immobilization rates were higher for eosino…

Regulation of phospholipase D in HL-60 granulocytes. Activation by phorbol esters, diglyceride, and calcium ionophore via protein kinase- independent mechanisms.

It has recently been demonstrated that the chemotactic peptide N-formyl-Met-Leu-Phe activates phospholipase D (PLD) in dimethyl sulfoxide-differentiated HL-60 granulocytes to produce phosphatidic acid (PA) and, in the presence of ethanol, phosphatidylethanol (PEt) (Pai, J.-K., Siegel, M. I., Egan, R. W., and Billah, M. M. (1988) J. Biol. Chem. 263, 12472-12477). We now report that biologically active phorbol esters, a cell-permeable diacylglycerol, 1-oleoyl-2-acetylglycerol (OAG), and calcium ionophore A23187 are also potent inducers of PLD in these HL-60 granulocytes. HL-60 granulocytes have …

The DNA synthetic response of normal and abnormal human lymphocytes to mevalonic acid: the role of granulocytes as a helper population.

In order to investigate the role of neutrophils in the DNA synthetic response of human peripheral blood lymphocytes to mevalonic acid, we obtained preparations of both cells each free of cross-contamination by the other. Purified lymphocytes respond poorly to mevalonic acid, but their response can be significantly enhanced by one half their number of neutrophils. Preincubation of lymphocytes with neutrophils for 24 hr, even in the absence of mevalonic acid, further increases the lymphocyte response. We have been unable to demonstrate the production by granulocytes of either an intracellular or…

Functional and metabolic activity of granulocytes from patients with adult respiratory distress syndrome. Evidence for activated neutrophils in the pulmonary circulation.

Although it has been proposed that the circulating granulocyte (PMN) is an effector cell that causes pulmonary vascular injury in the adult … +/- 31 cpm X 10(3); mean peak CL of normal PMNs, 105 +/- 16 cpm X 10(3); p = 0.04), suggesting that granulocytes from patients with ARDS are likely to generate increased quantities of active oxygen metabolites when stimulated. The chemotactic and chemiluminescence responses of PMNs from patients with ARDS were much greater than those of critically ill patients …

[Human granulocytic anaplasmosis: an autochthonous tick-borne disease with a potentially severe course].

Human granulocytic anaplasmosis (HGA) is caused by Anaplasma phagocytophilum. In the Netherlands, the bacterium is present in a few percent of Ixodes ricinus ticks, but only a specific subvariant is associated with human disease. Although the infection is often asymptomatic, the clinical course can be severe and unpredictable. Here, we describe three recent Dutch cases: two autochthonous cases with a severe course and one case acquired in the United States. All patients recovered rapidly after initiation of doxycycline following the final diagnosis. Awareness of tick-borne diseases other than

MMP-9 affects dural cell composition and granulocyte accumulation during neuroinflammation.

INTRODUCTION: Matrix metalloproteinases MMP-2 and MMP-9 modulate inflammatory processes at the blood-brain barrier (BBB), but their presence and function in the dura mater remain unclear. We therefore investigated their contribution to immune regulation at this site during neuroinflammation. METHODS: We analyzed dura mater from naïve and experimental autoimmune encephalomyelitis (EAE) mice using immunofluorescence, gelatin zymography, flow cytometry, and single-nucleus RNA sequencing (snRNA-seq). Comparisons were performed between wild-type (WT) and Mmp9-/- mice to define gelatinase expressio

Comparative immunological study on granulocyte populations in the Leydig organ of two elasmobranch species.

Elasmobranchs are the most primitive jawed vertebrates, and their immune system is similar to those of amniotes. Therefore, sharks and rays represent excellent models for investigating the evolution of immune system components and functions. In addition to the typical lymphoid tissues, namely the thymus and spleen, elasmobranchs have Leydig (LO) and epigonal organs instead of bone marrow. The LO is located between the submucosa and muscular layers of the esophagus. Here, we report the cell composition of the LO in two elasmobranch species, the thornback ray (Raja clavata) and the small-spotted

Granulocyte abundance and maturation state at diagnosis predicts treatment-free remission in CML.

Treatment-free remission (TFR) has become a therapeutic objective for selected chronic-phase chronic myeloid leukemia (CP CML). However, no standardized biomarker is yet in clinical use. In this multi-center study, we explored the potential of bone marrow (BM) cytomorphology given its global accessibility and integral role in clinical diagnostics. We included diagnostic BM aspirate samples of 113 CP CML patients from seven clinical sites having attempted first TKI discontinuation. We digitized cytomorphological slides into 100x-magnified high-resolution images and analyzed these with deep lear

Granulocyte colony-stimulating factor promotes regeneration of severed facial nerve in rats.

BACKGROUND AND AIM: The administration of growth and neurotrophic factors has been attempted experimentally as a new therapeutic strategy for severe facial paralysis. Granulocyte colony-stimulating factor (G-CSF) has an effect on the treatment of central nervous system injuries, such as cerebral infarction and spinal cord injury. This study aimed at examining the effects of G-CSF on facial nerve regeneration in rats. METHODS: The left facial nerve of rats was either partially resected (resection group) or severed and sutured (suture group) at the main trunk outside the temporal bone. In each

[A Case of Granulocyte-Colony Stimulating Factor-Producing Undifferentiated Sarcoma of the Transverse Colon].

We report a case of granulocyte-colony stimulating factor(G-CSF)-producing undifferentiated sarcoma of the transverse colon. A 80-year-old woman was referred to our hematology department after visiting her primary physician with chief complaints of decreased appetite and fatigue. An elevated white blood cell count was observed during examination. Further laboratory tests at our hospital revealed an elevated white blood cell count of 95,800/μL and a plasma G-CSF level of 895 pg/mL. The patient was referred to our department after a tumor lesion was found in the transverse colon during computed

Clinical Characteristics and Diagnosis of Nonaccelerating MDS/MPN-U Patient with Granulocyte Dysplasia.

BACKGROUND: The goal was to improve the clinical cognition of nonaccelerating myelodysplastic/myeloproliferative neoplasms-unclassifiable (M … d platelet 113 x 109/L. Blood smears showed granulocytosis and cells at various stages, polylobular granulocytes also can be seen. Bone marrow images show granulocytosis and dysplastic neutrophils, such as binuclear granulocyte, cyclic nuclear granulocyte, nuclear punch, cytoplasm vacuoles, polylobular granulocytes and so on. Bone marrow biopsy: Bone marrow pr …

Role of granulocyte colony stimulating factor in the treatment of cirrhosis of liver: a systematic review.

OBJECTIVE: We performed a systematic review to analyze the benefits of and risk factors associated with granulocyte colony stimulating factor (GCSF) in patients with liver cirrhosis. METHODS: PubMed, Scopus, and Embase were searched for randomized controlled trials and case-control studies that compared the use of GCSF with another treatment or control group. The Jadad and Newcastle-Ottawa scales were used to assess the risk of bias in the included studies. The primary outcome studied was mortality; and the secondary outcomes were the disease severity score, liver transplantation criteria, co

Current state and future opportunities in granulocyte colony-stimulating factor (G-CSF).

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… G-CSF is clearly responsible for the formation of 75% of granulocytes under basal conditions [ 7 ]. GM-CSF, on the other hand, did not appear to affect the number of mature granulocytes, but instead was essential for the functional activity of macrophages, particularly those in the lung [ 8 ]. … G-CSF and clinical application In chemotherapy-induced neutropenia, the bone marrow reserve of granulocytes is decreased. …

A Survey of Oncologists' Perceptions and Opinions Regarding the Use of Granulocyte Colony-Stimulating Factors.

The purpose of the study is to describe oncologists' perceptions and opinions about patient eligibility, guidelines, and barriers for use of granulocyte colony-stimulating factor (G-CSF), overall and stratified by their affiliation with the Oncology Care Model (OCM). In May 2018, we invited and recruited practicing US oncologists from a national database for an online survey. Level of agreement was identified using a seven-point scale, ranging from strongly disagree to strongly agree. Of 200 participating oncologists, 70 were OCM-affiliated. Overall, 65% of oncologists agreed or strongly agree