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Bone marrow necrosis AML

Inna M Yasinska, Isabel Gonçalves Silva, Svetlana S Sakhnevych, Laura Ruegg, Rohanah Hussain, Giuliano Siligardi, Walter Fiedler, Jasmin Wellbrock, Marco Bardelli, Luca Varani, Ulrike Raap, Steffen Berger, Bernhard F Gibbs, Elizaveta Fasler-Kan, Vadim V Sumbayev
High mobility group box 1 (HMGB1) is a non-histone protein localised in the cell nucleus, where it interacts with DNA and promotes nuclear transcription events. HMGB1 levels are elevated during acute myeloid leukaemia (AML) progression followed by participation of this protein in triggering signalling events in target cells as a pro-inflammatory stimulus. This mechanism was hypothesised to be employed as a survival pathway by malignant blood cells and our aims were therefore to test this hypothesis experimentally...
2018: Oncoimmunology
Adrien Quintela, Pierre Sujobert, Isabelle Tigaud, Sandrine Hayette, Martine Ffrench, Gilles Salles, Xavier Thomas, Adriana Plesa
Bone marrow necrosis (BMN) in acute leukemia is a rare histopathological entity at the time of initial diagnosis. However, it represents an important diagnostic and prognostic challenge. Two cases of BMN are reported: a 44-year-old patient with B cell precursor (BCP) acute lymphoblastic leukemia (ALL) and a 27-year-old man with FAB-M5 acute myeloid leukemia (AML) who both presented with bone marrow failure and extensive necrosis. From these clinical cases, we conducted a brief review of the literature.
2017: Oncology and Therapy
Isaac Chambers, Phu Truong, K James Kallail, William Palko
Acute myeloid leukemia (AML) is the most common leukemia in adults. In rare cases, bone marrow necrosis (BMN) and osteolytic lesions are presenting features of AML. The following case describes a patient with known polycythemia vera (PV) that presented with signs of multiple myeloma, including hypercalcemia, anemia, and lytic lesions of the thoracic spine and skull. Laboratory workup was not indicative of myeloma. A bone marrow biopsy was performed, which revealed extensive BMN and initial pathology was consistent with metastatic carcinoma...
2016: Curēus
Kui Song, Min Li, Xiaojun Xu, L I Xuan, Guinian Huang, Qifa Liu
Altered glucose metabolism has been described as a cause of chemoresistance in multiple tumor types. The present study aimed to identify the expression profile of glucose metabolism in drug-resistant acute myeloid leukemia (AML) cells and provide potential strategies for the treatment of drug-resistant AML. Bone marrow and serum samples were obtained from patients with AML that were newly diagnosed or had relapsed. The messenger RNA expression of hypoxia inducible factor (HIF)-1α, glucose transporter (GLUT)1, and hexokinase-II was measured by quantitative polymerase chain reaction...
July 2016: Oncology Letters
Gaetano Paone, Georg Stüssi, Marco Pons, Luca Giovanella, Luca Ceriani
A 83-year-old patient with inflammatory syndrome, unknown fever, and intense lumbar pain underwent diagnostic imaging for suspicion of spondylodiscitis. Fused F-FDG PET/MRI images showed heterogeneous hypermetabolism in the lumbar spine characterized by infiltrative lesions and adjacent necrotic tissue. Peripheral blood analysis revealed leukoerythroblastic changes, whereas bone marrow biopsy was highly hypercellular and revealed an acute myeloid leukemia with 70% infiltration of blasts of erythroid lineage...
October 2015: Clinical Nuclear Medicine
Talha Badar, Aditya Shetty, Carlos Bueso-Ramos, Jorge Cortes, Marina Konopleva, Gautam Borthakur, Sherry Pierce, Xuelin Huang, Hsiang-Chun Chen, Tapan Kadia, Naval Daver, Courtney Dinardo, Susan O'Brien, Guillermo Garcia-Manero, Hagop Kantarjian, Farhad Ravandi
Bone marrow necrosis (BMN) is characterized by infarction of the medullary stroma, leading to marrow necrosis with preserved cortical bone. In reported small series, BMN in hematological malignancies is associated with poor prognosis. We sought to find the impact of BMN on clinical outcome in a relatively larger cohort of patients with acute leukemias. Overall we evaluated 1,691 patients; 1,051 with acute myeloid leukemia (AML) and 640 with acute lymphocytic leukemia referred to our institution between 2002 and 2013...
September 2015: American Journal of Hematology
J C Huang, S K Basu, X Zhao, S Chien, M Fang, V G Oehler, F R Appelbaum, P S Becker
Bone marrow-derived mesenchymal stromal cells (BM-MSCs) play a fundamental role in the BM microenvironment (BME) and abnormalities of these cells may contribute to acute myeloid leukemia (AML) pathogenesis. The aim of the study was to characterize the cytokine and gene expression profile, immunophenotype and cytogenetics of BM-MSCs from AML patients compared to normal BM-MSCs from healthy donors. AML BM-MSCs showed decreased monocyte chemoattractant protein-1 levels compared to normal BM-MSCs. AML BM-MSCs expressed similar β1 integrin, CD44, CD73, CD90 and E-cadherin compared to normal BM-MSCs...
2015: Blood Cancer Journal
John F DiPersio, Harry P Erba, Richard A Larson, Selina M Luger, Martin S Tallman, Jeffrey M Brill, Gregoire Vuagniaux, Elisabeth Rouits, J Mel Sorensen, Claudio Zanna
BACKGROUND: Treatment of acute myeloid leukemia (AML) remains difficult owing to the development of treatment resistance, which might be overcome through antagonists of inhibitors of apoptosis proteins (IAPs). PATIENTS AND METHODS: The present multicenter, open-label, dose-escalation study aimed to evaluate the tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of Debio1143 (formerly AT-406), a new IAP antagonist, when given along with a standard "7 plus 3 regimen" of daunorubicin and cytarabine to poor-risk patients with AML during the induction cycle...
July 2015: Clinical Lymphoma, Myeloma & Leukemia
Håkon Reikvam, Anita Ryningen, Lars Rune Sæterdal, Ina Nepstad, Brynjar Foss, Øystein Bruserud
Bone marrow stromal cells support both normal and malignant hematopoiesis. Τhis support is mediated through the local cytokine network and by direct cell‑cell interactions mediated via adhesion molecules and the formation of gap junctions by connexins. Previous studies on connexins in human acute myeloid leukemia (AML) have mainly focused on the investigation of leukemia cell lines. In the present study, we therefore investigated the expression of various connexins at the protein (i.e., cell surface expression) and mRNA level in primary human AML cells...
March 2015: International Journal of Molecular Medicine
Quan-shun Wang, Yao Wang, Hai-yan Lv, Qing-wang Han, Hui Fan, Bo Guo, Li-li Wang, Wei-dong Han
We conducted a clinical trial to assess the feasibility and efficacy of CD33-directed chimeric antigen receptor-modified T cells (CART-33) for the treatment of refractory acute myeloid leukemia (AML). A 41-year-old male patient with AML was enrolled and received a total of 1.12 × 10(9) autologous CART-33 cells, of which ~38% were transduced with CAR. The CART-33 infusion alone induced rigorous chills and fevers; drastic fluctuations of his preexisting pancytopenia; elevated serum cytokine levels, including interleukin (IL)-6, IL-8, tumor necrosis factor-α, and interferon-γ; slight transient hyperbilirubinemia within 2 weeks; a subsequent intermittent moderate fever; and reversed fluctuation of the pancytopenia...
January 2015: Molecular Therapy: the Journal of the American Society of Gene Therapy
Po Y Mak, Duncan H Mak, Vivian Ruvolo, Rodrigo Jacamo, Steven M Kornblau, Hagop Kantarjian, Michael Andreeff, Bing Z Carter
Overexpression of the apoptosis repressor with caspase recruitment domain (ARC, also termed NOL3) protein predicts adverse outcome in patients with acute myeloid leukaemia (AML) and confers drug resistance to AML cells. The second mitochondrial-derived activator of caspases (SMAC, also termed DIABLO) mimetic, birinapant, promotes extrinsic apoptosis in AML cells. SMAC mimetics induce cleavage of cellular inhibitor of apoptosis (cIAP) proteins, leading to stabilization of the nuclear factor-κB (NF-κB)-inducing kinase (MAP3K14, also termed NIK) and activation of non-canonical NF-κB signalling...
November 2014: British Journal of Haematology
Chutika Srisuttiyakorn, Jennifer Reeve, Swapna Reddy, Suguru Imaeda, Rossitza Lazova
Subcutaneous histiocytoid Sweet’s syndrome is a rare variant of histiocytoid Sweet’s syndrome (SS). We present a 68-year-old woman with subcutaneous histiocytoid SS in association with refractory myelodysplastic syndrome transformed to acute myeloblastic leukemia (AML), status post induction chemotherapy and with persistent blasts (50%) in the bone marrow and blood, accompanied with neutropenia. The patient presented to the emergency room with fever and altered mental status. Clinical examination revealed approximately 20 scattered 0...
May 2014: Journal of Cutaneous Pathology
Michael Daskalakis, Marcelo Caballero
No abstract text is available yet for this article.
April 3, 2014: Blood
Chindu Govindaraj, Peter Tan, Patricia Walker, Andrew Wei, Andrew Spencer, Magdalena Plebanski
PURPOSE: Acute myeloid leukemia (AML) provides an environment that enables immune suppression, resulting in functionally defective effector T cells; regulatory T cells (Treg) are significant contributors to the impaired antitumor immune response. As TNF is present at high levels in AML and TNF receptor-2 (TNFR2)-expressing Tregs identify highly functional Tregs, we examine the hypothesis that TNFR2(+) Tregs are a relevant Treg subset in this cancer. We also determine the effect of the novel combinatorial therapy of the demethylating agent, azacitidine with the histone deacetylase inhibitor, panobinostat on Tregs, particularly TNFR2(+) Tregs...
February 1, 2014: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Leah A Marquez-Curtis, Neeta Shirvaikar, A Robert Turner, Imran Mirza, Amir Surmawala, Loree M Larratt, Anna Janowska-Wieczorek
Membrane type-1 matrix metalloproteinase (MT1-MMP) has been implicated in tumor invasion, as well as trafficking of normal hematopoietic cells, and acts as a physiologic activator of proMMP-2. In this study we examined MT1-MMP expression in primary acute myeloid leukemia (AML) cells. Because tumor necrosis factor (TNF)-α is known to be elevated in AML, we also investigated the effect of TNF-α on MT1-MMP expression. We found (i) MT1-MMP mRNA expression in 41 out of 43 primary AML samples tested; (ii) activation of proMMP-2 in co-cultures of AML cells with normal bone marrow stromal cells; and (iii) inhibition of proMMP-2 activation and trans-Matrigel migration of AML cells by gene silencing using MT1-MMP siRNA...
2012: Cancers
Wenhui Zhang, Kaikai Chi, Yin Zhang, Baogen Ma, Jie Shi, Yuqing Chen, Pingchong Lei, Yulong Li, Kai Sun
Introduction: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) down-regulation by preferentially expressed antigen of melanoma (PRAME) is a general phenomenon in different types of solid tumours, but research on the correlation between PRAME and TRAIL gene expression in leukaemia patients is rare. Method: PRAME and TRAIL expression was detected in bone marrow samples from 80 newly diagnosed acute leukaemia (AL) patients and 40 chronic myeloid leukaemia (CML) patients using TaqMan-based real-time quantitative PCR methods, and a linear correlation analysis was performed on their levels of expression...
2013: Acta Haematologica
Gianni Capalbo, Thea Mueller-Kuller, Steffen Koschmieder, Hans-Ulrich Klein, Oliver G Ottmann, Dieter Hoelzer, Urban J Scheuring
The gene product of the zinc finger CCCH-type containing 15 (ZC3H15) gene, an immediate early erythropoietin response gene (synonymous: LEREPO4), was further characterized. ZC3H15 was expressed ubiquitously in all human tissues tested by northern blotting and showed mainly a diffuse cytoplasmic distribution by immune fluorescence microscopy and western blotting of subcellular protein fractions. The expression of ZC3H15 was downregulated effectively in HeLa cells to ≤13% of the control by transfection of specific small interfering RNA (siRNA)...
July 2013: International Journal of Oncology
U Bacher, C Haferlach, S Schnittger, W Kern, M M Ott, T Haferlach
Due to the heterogeneity of these disorders, the diagnosis of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) requires a broad spectrum of laboratory techniques: cytomorphology, immunophenotyping, chromosome banding analysis, fluorescence in situ hybridization, and molecular genetics. The cytomorphological leukemia subtypes can be indicative for distinct genetic alterations and contribute to the guidance of the further diagnostic process. Immunophenotyping allows to define the hematological lineage and to characterize the leukemia-associated immunophenotype as basis for follow up investigation...
November 2012: Der Pathologe
Ikenna Osuorji, Lyle Goldman
Bone marrow necrosis (BMN) is defined as necrosis of the myeloid tissues and stroma without involvement of the cortical bone. We report a case of 66-year-old male with AML-M4 (FAB classification) who was given induction chemotherapy with cytarabine and daunorubicin. Filgrastim at 480 micrograms was administered on days 15-19 to shorten the duration of neutropenia. Consequently patient developed severe pelvic bone pain, leukoerythroblastosis, and severe leukocytosis. Repeat bone marrow aspiration and biopsy on day 21 confirmed bone marrow necrosis...
2012: Case Reports in Hematology
L Van Crombrugge, G De Vos, C Vanclooster, M Lemmerling, T Kerre
INTRODUCTION AND AIM: Sinonasal malignant neoplasms are uncommon, with an annual incidence of less than 1/100,000. About 80% of these are squamous cell carcinoma. Adenocarcinoma and adenoid cystic carcinoma are next in frequency. Lymphoma of the nasal cavity, paranasal sinuses and nasopharynx are rare, constituting less than 5% of all extranodal lymphomas. CASE REPORT: A 47-year-old man was referred to our hospital because of severe headache and progressive facial pain...
2012: B-ENT
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