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Large granulocytic leukemia

W Liu, M Wu, Z Huang, J Lian, J Chen, T Wang, A Y H Leung, Y Liao, Z Zhang, Q Liu, K Yen, S Lin, L I Zon, Z Wen, Y Zhang, W Zhang
The c-MYB transcription factor is a key regulator of hematopoietic cell proliferation and differentiation, and dysregulation of c-MYB activity often associates with various hematological disorders. Yet, its pathogenic role remains largely unknown due to lack of suitable animal models. Here, we report a detail characterization of a c-myb-gfp transgenic zebrafish harboring c-Myb hyperactivity (named c-myb(hyper)). This line exhibits abnormal granulocyte expansion that resembles human myelodysplastic syndrome (MDS) from embryonic stage to adulthood...
July 26, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Imane Azzaoui, Fabrice Uhel, Delphine Rossille, Celine Pangault, Joelle Dulong, Jerome Le Priol, Thierry Lamy, Roch Houot, Steven Le Gouill, Guillaume Cartron, Pascal Godmer, Krimo Bouabdallah, Noel Milpied, Gandhi Damaj, Karin Tarte, Thierry Fest, Mikael Roussel
In diffuse large B-cell lymphoma (DLBCL), the number of circulating monocytes and neutrophils represents an independent prognostic factor. These cell subsets include monocytic and granulocytic myeloid-derived suppressor cells (M- and G-MDSCs) defined by their ability to suppress T-cell responses. MDSCs are a heterogeneous population described in inflammatory and infectious diseases and in numerous tumors including multiple myeloma, chronic lymphocytic leukemia, and DLBCL. However, their mechanisms of action remain unclear...
August 25, 2016: Blood
A C Herman, D A Monlish, M P Romine, S T Bhatt, S Zippel, L G Schuettpelz
Toll-like receptor 2 (TLR2) is a member of the TLR family of receptors that play a central role in innate immunity. In addition to regulating effector immune cells, where it recognizes a wide variety of pathogen-associated and nonpathogen-associated endogenous ligands, TLR2 is expressed in hematopoietic stem cells (HSCs). Its role in HSCs, however, is not well understood. Furthermore, augmented TLR2 signaling is associated with myelodysplastic syndrome, an HSC disorder characterized by ineffective hematopoiesis and a high risk of transformation to leukemia, suggesting that aberrant signaling through this receptor may have clinically significant effects on HSCs...
2016: Blood Cancer Journal
Nathan Gossai, Rachel Cafferty, Brenda Weigel
Granulocytic sarcoma (GS) is a rare manifestation of myeloid proliferation, characterized by formation of a mass comprised of immature cells of myeloid origin. Orbital granulocytic sarcoma is rarer still, with only a small fraction of GS patients having orbital involvement. Given the rarity of orbital GS, no unified therapy plan has been identified, as large prospective trials are not feasible, but it is widely accepted that patients with GS ought to be treated with systemic intensive chemotherapy consistent with standard of care regimens for acute myelogenous leukemia (AML) or chronic myelogenous leukemia (CML)...
July 2016: Current Treatment Options in Oncology
Maksim Klimiankou, Sabine Mellor-Heineke, Cornelia Zeidler, Karl Welte, Julia Skokowa
Acquired mutations in the intracellular part of CSF3R (colony stimulating factor 3 receptor, granulocyte) have been detected with a frequency of more than 30% in severe congenital neutropenia (CN) patients. CN is a preleukemic syndrome with a risk of approximately 20% to develop leukemia. More than 80% of CN patients who develop acute myeloid leukemia or myelodysplastic syndrome reveal CSF3R mutations, suggesting that they are involved in leukemogenesis. Using deep-sequencing technology, we were able to analyze large cohorts of CN patients for the entire CSF3R sequence as well as to identify cell clones carrying mutations in the intracellular part of CSF3R with very high sensitivity...
April 2016: Annals of the New York Academy of Sciences
Taghreed Hirz, Charles Dumontet
Neutrophils are the most abundant (40% to 75%) type of white blood cells and among the first inflammatory cells to migrate towards the site of inflammation. They are key players in the innate immune system and play major roles in cancer biology. Neutrophils have been proposed as key mediators of malignant transformation, tumor progression, angiogenesis and in the modulation of the antitumor immunity; through their release of soluble factors or their interaction with tumor cells. To characterize the specific functions of neutrophils, a fast and reliable method is coveted for in vitro isolation of neutrophils from human blood...
2016: Journal of Visualized Experiments: JoVE
Li-Fen Huang, Chia-Chun Tan, Ju-Fang Yeh, Hsin-Yi Liu, Yu-Kuo Liu, Shin-Lon Ho, Chung-An Lu
Plant-based expression systems have emerged as a competitive platform in the large-scale production of recombinant proteins. By adding a signal peptide, αAmy3sp, the desired recombinant proteins can be secreted outside transgenic rice cells, making them easy to harvest. In this work, to improve the secretion efficiency of recombinant proteins in rice expression systems, various signal peptides including αAmy3sp, CIN1sp, and 33KDsp have been fused to the N-terminus of green fluorescent protein (GFP) and introduced into rice cells to explore the efficiency of secretion of foreign proteins...
2015: PloS One
Wasithep Limvorapitak, Thana Khawcharoenporn
A 6-year retrospective cohort study was conducted among Thai hematologic malignancy (HM) patients receiving intensive chemotherapy. Of the 145 eligible patients receiving 893 chemotherapy sessions, 46.9% were female, median age was 52 years, and the most common HM diagnosis was diffuse large B-cell lymphoma (46.2%). Febrile neutropenia (FN) occurred in 14.9% of chemotherapy sessions with an incidence of 24.8 per 1,000 chemotherapy cycles per year. Independent factors associated with FN were receiving the first chemotherapy cycle [adjusted hazard ratio (aHR) 4...
2015: Asian Pacific Journal of Cancer Prevention: APJCP
Xiaobang Hu, Imran Shahab, Isador H Lieberman
Study Design Case report. Objective Myeloid sarcoma (also known as chloroma) is a rare, extramedullary tumor composed of immature granulocytic cells. It may occur early in the course of acute or chronic leukemia or myeloproliferative disorders. Spinal cord invasion by myeloid sarcoma is rare. The authors report a rare case of spinal myeloid sarcoma presenting as cervical radiculopathy. Methods A previously healthy 43-year-old man presented with progressive neck, right shoulder, and arm pain. Cervical magnetic resonance imaging (MRI) revealed a very large enhancing extradural soft tissue mass extending from C7 through T1, with severe narrowing of the thecal sac at the T1 level...
June 2015: Global Spine Journal
Xiao-Rong Ma, Jin Wang, Wang-Gang Zhang, Yin-Xia Chen, Xing-Mei Cao, Ai-Li He, Jie Liu, Jian-Li Wang, Liu-Fang Gu, Bo Lei, Peng-Yu Zhang, Wan-Hong Zhao, Yun Yang, Fang-Xia Wang, Yan Xu
OBJECTIVE: To explore the clinical efficacy and adverse effects of GHA(G-CSF+homoharringtonin+cytarabine C) and new combined priming chemotherapeutic regimens(GHAA/GHTA) with high efficacy and low toxicity for treatment of relapsed and refractory acute myeloid leukemia(AML) and myelodysplastic syndrome(MDS), and to analyze the relation of above-mentioned regimens with the expression of co-stimuolating molecule B7.1. METHODS: Standard GHA regimen consisting of G-CSF: 100 µg/(m2·d) subcutaneous injection, d 0-14; homoharringtonine: 1...
April 2015: Zhongguo Shi Yan Xue Ye Xue za Zhi
R F Olsson, B R Logan, S Chaudhury, X Zhu, G Akpek, B J Bolwell, C N Bredeson, C C Dvorak, V Gupta, V T Ho, H M Lazarus, D I Marks, O T H Ringdén, M C Pasquini, J R Schriber, K R Cooke
Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23,272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared with bone marrow grafts (2.5 vs 7.3%; P<0.001). A fourfold increase of PGF was observed in myeloproliferative disorders compared with acute leukemia (P<0...
August 2015: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Sunyoung Lee, Pouya Khankhanian, Carlos Salama, Maritza Brown, Joseph Lieber
Pseudo-Pelger-Huët anomaly (PHA) refers to mono- or bi-lobed granulocytes, reportedly observed in patients with severe infections and inflammation or hematological malignancies including myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Dysplastic changes in granulocytes are typical manifestations in MDS and granulocytic leukemias. Here, we report the unique case of a patient found to have human granulocytic anaplasmosis (HGA), a tick-borne disease caused by Anaplasma phagocytophilum, a Gram-negative coccobacillus...
July 2015: International Journal of Hematology
Ariz Akhter, Jay L Patel, Fahad Farooq, Abid Qureshi, Meer-Shahbani Taher-Rad, Ghaleb Elyamany, Ali M Al-Zahrani, Fariborz Rashid-Kolvear, Adnan Mansoor
MicroRNA (MIR) signatures are critical to pathobiology and prognosis of acute myeloid leukemia (AML). MIR223 is expressed at low levels in progenitor cells, whereas high expression is induced by granulocytic differentiation. Novel-targeted therapies through epigenetic manipulation of MIR223 regulators are being explored in AML but correlative data between established clinical prognostic markers and MIR223 expression in AML is lacking. MIR223 has inverse relationship with LMO2 protein expression and our group has recently reported a close association between LMO2 protein expression and chromosomal findings in AML patients...
November 2015: Applied Immunohistochemistry & Molecular Morphology: AIMM
Franco Locatelli, Charlotte M Niemeyer
Juvenile myelomonocytic leukemia (JMML) is a unique, aggressive hematopoietic disorder of infancy/early childhood caused by excessive proliferation of cells of monocytic and granulocytic lineages. Approximately 90% of patients carry either somatic or germline mutations of PTPN-11, K-RAS, N-RAS, CBL, or NF1 in their leukemic cells. These genetic aberrations are largely mutually exclusive and activate the Ras/mitogen-activated protein kinase pathway. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the therapy of choice for most patients with JMML, curing more than 50% of affected children...
February 12, 2015: Blood
Matthias Piesche, Vincent T Ho, Haesook Kim, Yukoh Nakazaki, Michael Nehil, Nasser K Yaghi, Dmitriy Kolodin, Jeremy Weiser, Peter Altevogt, Helena Kiefel, Edwin P Alyea, Joseph H Antin, Corey Cutler, John Koreth, Christine Canning, Jerome Ritz, Robert J Soiffer, Glenn Dranoff
PURPOSE: The graft-versus-leukemia (GVL) reaction is an important example of immune-mediated tumor destruction. A coordinated humoral and cellular response accomplishes leukemia cell killing, but the specific targets remain largely uncharacterized. To learn more about the antigens that elicit antibodies during GVL reactions, we analyzed patients with advanced myelodysplasia (MDS) and acute myelogenous leukemia (AML) who received an autologous, granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor cell vaccine early after allogeneic hematopoietic stem cell transplantation (HSCT)...
March 1, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Philip A Beer, David J H F Knapp, Nagarajan Kannan, Paul H Miller, Sonja Babovic, Elizabeth Bulaeva, Nima Aghaeepour, Gabrielle Rabu, Shabnam Rostamirad, Kingsley Shih, Lisa Wei, Connie J Eaves
Disrupted IKAROS activity is a recurrent feature of some human leukemias, but effects on normal human hematopoietic cells are largely unknown. Here, we used lentivirally mediated expression of a dominant-negative isoform of IKAROS (IK6) to block normal IKAROS activity in primitive human cord blood cells and their progeny. This produced a marked (10-fold) increase in serially transplantable multipotent IK6(+) cells as well as increased outputs of normally differentiating B cells and granulocytes in transplanted immunodeficient mice, without producing leukemia...
November 11, 2014: Stem Cell Reports
James M Hughes, Beatrice Salvatori, Federico M Giorgi, Irene Bozzoni, Alessandro Fatica
CCAAT/enhancer-binding protein-α (CEBPA) is a critical regulator of myeloid differentiation. Disruption of CEBPA function contributes to the development of acute myeloid leukemia (AML). CEBPA regulates a large number of protein coding genes of which several were shown to contribute to CEBPA function. In this study, we expand the analysis of CEBPA transcriptional targets to the newly identified class of long non-coding RNAs. We show that lncRNAs are a main component of the transcriptional program driven by C/EBPα and that many of these are also induced during granulocytic differentiation of AML cell lines supporting their relevance in proliferation arrest and differentiation...
2014: Journal of Hematology & Oncology
Jan Jacques Michiels, Zwi Berneman, Wilfried Schroyens, Hendrik De Raeve
The Polycythemia Vera Study Group (PVSG) and WHO classifications distinguished the Philadelphia (Ph(1)) chromosome-positive chronic myeloid leukemia from the Ph(1)-negative myeloproliferative neoplasms (MPN) essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (MF) or primary megakaryocytic granulocytic myeloproliferation (PMGM). Half of PVSG/WHO-defined ET patients show low serum erythropoietin levels and carry the JAK2(V617F) mutation, indicating prodromal PV. The positive predictive value of a JAK2(V617F) PCR test is 95% for the diagnosis of PV, and about 50% for ET and MF...
2015: Acta Haematologica
K Sakashita, I Kato, T Daifu, S Saida, H Hiramatsu, Y Nishinaka, Y Ebihara, F Ma, K Matsuda, S Saito, K Hirabayashi, T Kurata, L T N Uyen, Y Nakazawa, K Tsuji, T Heike, T Nakahata, K Koike
Using serum-containing culture, we examined whether AGM-S3 stromal cells, alone or in combination with hematopoietic growth factor(s), stimulated the proliferation of CD34(+) cells from patients with juvenile myelomonocytic leukemia (JMML). AGM-S3 cells in concert with stem cell factor plus thrombopoietin increased the numbers of peripheral blood CD34(+) cells to approximately 20-fold of the input value after 2 weeks in nine JMML patients with either PTPN11 mutations or RAS mutations, who received allogeneic hematopoietic transplantation...
March 2015: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
D Brigger, T Proikas-Cezanne, M P Tschan
Members of the WD-repeat protein interacting with phosphoinositides (WIPI) family are phosphatidylinositol 3-phosphate (PI3P) effectors that are essential for the formation of autophagosomes. Autophagosomes, unique double-membraned organelles, are characteristic for autophagy, a bulk degradation mechanism with cytoprotective and homeostatic function. Both, WIPI-1 and WIPI-2 are aberrantly expressed in several solid tumors, linking these genes to carcinogenesis. We now found that the expression of WIPI-1 was significantly reduced in a large cohort of 98 primary acute myeloid leukemia (AML) patient samples (complex karyotypes; t(8;21); t(15,17); inv(16))...
2014: Cell Death & Disease
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