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https://www.readbyqxmd.com/read/29773600/the-interleukin-3-receptor-cd123-targeted-sl-401-mediates-potent-cytotoxic-activity-against-cd34-cd123-cells-from-acute-myeloid-leukemia-myelodysplastic-syndrome-patients-and-healthy-donors
#1
Rajeswaran Mani, Swagata Goswami, Bhavani Gopalakrishnan, Rahul Ramaswamy, Ronni Wasmuth, Minh Tranh, Xiaokui Mo, Amber Gordon, Donna Bucci, David M Lucas, Alice Mims, Christopher Brooks, Adrienne Dorrance, Alison Walker, William Blum, John C Byrd, Gerard Lozanski, Sumithira Vasu, Natarajan Muthusamy
Diseases with clonal hematopoiesis such as myelodysplastic syndrome and acute myeloid leukemia have high rates of relapse. Only a small subset of acute myeloid leukemia patients are cured with chemotherapy alone. Relapse in these diseases occurs at least in part due to the failure to eradicate leukemic stem cells or hematopoietic stem cells in myelodysplastic syndrome. CD123, the alpha chain of the interleukin-3 receptor heterodimer, is expressed on the majority of leukemic stem cells and myelodysplastic syndrome hematopoietic stem cells and in 80% of acute myeloid leukemia...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29772458/phenotyping-and-target-expression-profiling-of-cd34-cd38-and-cd34-cd38-stem-and-progenitor-cells-in-acute-lymphoblastic-leukemia
#2
Katharina Blatt, Ingeborg Menzl, Gregor Eisenwort, Sabine Cerny-Reiterer, Harald Herrmann, Susanne Herndlhofer, Gabriele Stefanzl, Irina Sadovnik, Daniela Berger, Alexandra Keller, Alexander Hauswirth, Gregor Hoermann, Michael Willmann, Thomas Rülicke, Heinz Sill, Wolfgang R Sperr, Christine Mannhalter, Junia V Melo, Ulrich Jäger, Veronika Sexl, Peter Valent
Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34+ /CD38- LSCs in patients with Ph+ ALL (n = 22) and Ph- ALL (n = 27) by multi-color flow cytometry and qPCR. ALL LSCs expressed CD19 (B4), CD44 (Pgp-1), CD123 (IL-3RA), and CD184 (CXCR4) in all patients tested...
May 14, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29742552/subcutaneous-panniculitis-like-t-cell-lymphoma-versus-lupus-erythematosus-panniculitis-distinction-by-means-of-the-periadipocytic-cell-proliferation-index
#3
Panitta Sitthinamsuwan, Penvadee Pattanaprichakul, Jitsupa Treetipsatit, Tawatchai Pongpruttipan, Sanya Sukpanichnant, Laura B Pincus, Timothy H McCalmont
The distinction between subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and lupus erythematosus (LE) panniculitis is remarkably challenging. Rimming by lymphocytes with an elevated Ki-67 cell proliferation index has been forwarded as a potential diagnostic finding in biopsies of SPTCL but has not been rigorously compared with biopsies from patients with LE panniculitis. Nineteen and 17 examples of SPTCL and LE panniculitis, respectively, were evaluated for periadipocytic rimming by lymphocytes expressing Ki-67, CD8, and βF1 and for attributes associated with LE, including clusters of CD123-positive cells...
May 2, 2018: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/29720577/universal-monitoring-of-minimal-residual-disease-in-acute-myeloid-leukemia
#4
Elaine Coustan-Smith, Guangchun Song, Sheila Shurtleff, Allen Eng-Juh Yeoh, Wee Joo Chng, Siew Peng Chen, Jeffrey E Rubnitz, Ching-Hon Pui, James R Downing, Dario Campana
BACKGROUND: Optimal management of acute myeloid leukemia (AML) requires monitoring of treatment response, but minimal residual disease (MRD) may escape detection. We sought to identify distinctive features of AML cells for universal MRD monitoring. METHODS: We compared genome-wide gene expression of AML cells from 157 patients with that of normal myeloblasts. Markers encoded by aberrantly expressed genes, including some previously associated with leukemia stem cells, were studied by flow cytometry in 240 patients with AML and in nonleukemic myeloblasts from 63 bone marrow samples...
May 3, 2018: JCI Insight
https://www.readbyqxmd.com/read/29720227/first-pediatric-experience-of-sl-401-a-cd123-targeted-therapy-in-patients-with-blastic-plasmacytoid-dendritic-cell-neoplasm-report-of-three-cases
#5
Weili Sun, Huaying Liu, Young Kim, Nicole Karras, Anna Pawlowska, Debbie Toomey, Wade Kyono, Paul Gaynon, Joseph Rosenthal, Anthony Stein
BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a highly aggressive hematological malignancy with extremely poor outcome. The median overall survival for adult patients is 9-13 months. Pediatric patients are exceedingly rare with an unclear clinical course. Currently, no standardized therapy has been established, although an acute lymphoblastic leukemia type of treatment appears to be more effective in those patients who are able to tolerate aggressive chemotherapy...
May 2, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29684687/arsenic-trioxide-inhibits-proliferation-and-induced-apoptosis-of-leukemia-stem-cells-with-drug-resistance
#6
Chunxia Liu, Hulai Wei, Xiaojian Yao, Bei Liu, Yaming Xi, Li Zhao
Acute myeloid leukemia (AML) patients show high relapse rates and some develop conventional chemotherapy resistance. Leukemia Stem Cells (LSCs) are the main player for AML relapses and drug resistance. K562/ADM cell, a leukemia resistant cell subtype, was used as leukemia multidrug resistant model to explore drug resistance of leukemia cells. We found that CD34+ CD38- , CD34+ CD38- CD123+ , cell surface markers of LSCs were significantly high expressed in K562/ADM cell, not in K562 cell with less drug resistance; compared with LSCs from K562, multidrug resistance protein P-gp and BCRP expression were significantly higher in K562/ADM cell...
March 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29665897/-effects-of-triptolide-combined-with-homoharringtonine-on-proliferation-and-apoptosis-of-kg-1%C3%AE-cells
#7
Xin Li, Jia-Yan Liu, Xiao-Hong Yuan, Zhen-Xing Lin, Yong Wu
OBJECTIVE: To investigate the effect and possible mechanism of low concentration of triptolide (TPL) combined with homoharringtonine (HHT) on the proliferation and apoptosis of KG-1α cells. METHODS: CCK-8 method was used to detect the antiproliferating effects of different concentrations of TPL and HHT single-use and combined use on KG-1α cells, and the combined index (CI) was calculated. The colony formation ability was also determined by methylcellulose colony formation assay, cell surface molecules, apoptosis rate and cell cycle changes were detected by flow cytometry...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29661755/a-cd123-targeting-antibody-drug-conjugate-imgn632-designed-to-eradicate-aml-while-sparing-normal-bone-marrow-cells
#8
Yelena Kovtun, Gregory E Jones, Sharlene Adams, Lauren Harvey, Charlene A Audette, Alan Wilhelm, Chen Bai, Lingyun Rui, Rassol Laleau, Fenghua Liu, Olga Ab, Yulius Setiady, Nicholas C Yoder, Victor S Goldmacher, Ravi V J Chari, Jan Pinkas, Thomas Chittenden
The outlook for patients with refractory/relapsed acute myeloid leukemia (AML) remains poor, with conventional chemotherapeutic treatments often associated with unacceptable toxicities, including severe infections due to profound myelosuppression. Thus there exists an urgent need for more effective agents to treat AML that confer high therapeutic indices and favorable tolerability profiles. Because of its high expression on leukemic blast and stem cells compared with normal hematopoietic stem cells and progenitors, CD123 has emerged as a rational candidate for molecularly targeted therapeutic approaches in this disease...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29515236/compound-car-t-cells-as-a-double-pronged-approach-for-treating-acute-myeloid-leukemia
#9
Jessica C Petrov, Masayuki Wada, Kevin G Pinz, Lulu E Yan, Kevin H Chen, Xiao Shuai, Hua Liu, Xi Chen, Lai-Han Leung, Huda Salman, Nabil Hagag, Fang Liu, Xun Jiang, Yupo Ma
Acute myeloid leukemia (AML) bears heterogeneous cells that can consequently offset killing by single-CAR-based therapy, which results in disease relapse. Leukemic stem cells (LSCs) associated with CD123 expression comprise a rare population that also plays an important role in disease progression and relapse. Here, we report on the robust anti-tumor activity of a compound CAR (cCAR) T-cell possessing discrete scFv domains targeting two different AML antigens, CD123, and CD33, simultaneously. We determined that the resulting cCAR T-cells possessed consistent, potent, and directed cytotoxicity against each target antigen population...
February 25, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29463552/integrated-pharmacokinetic-pharmacodynamic-model-of-a-bispecific-cd3xcd123-dart-molecule-in-nonhuman-primates-evaluation-of-activity-and-impact-of-immunogenicity
#10
Olivia Campagne, Audrey Delmas, Sylvain Fouliard, Marylore Chenel, Gurunadh R Chichili, Hua Li, Ralph Alderson, Jean-Michel Scherrmann, Donald E Mager
Purpose: Flotetuzumab (MGD006 or S80880) is a bispecific molecule that recognizes CD3 and CD123 membrane proteins, redirecting T cells to kill CD123-expressing cells for the treatment of acute myeloid leukemia. In this study, we developed a mathematical model to characterize MGD006 exposure-response relationships and to assess the impact of its immunogenicity in cynomolgus monkeys. Experimental Design: Thirty-two animals received multiple escalating doses (100-300-600-1,000 ng/kg/day) via intravenous infusion continuously 4 days a week...
February 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29444931/complete-remission-with-reduction-of-high-risk-clones-following-haploidentical-nk-cell-therapy-against-mds-and-aml
#11
Andreas T Björklund, Mattias Carlsten, Ebba Sohlberg, Lisa L Liu, Trevor Clancy, Mohsen Karimi, Sarah Cooley, Jeffrey S Miller, Monika Klimkowska, Marie Schaffer, Emma Watz, Kristina Wikström, Pontus Blomberg, Björn Engelbrekt Wahlin, Marzia Palma, Lotta Hansson, Per Ljungman, Eva Hellström-Lindberg, Hans-Gustaf Ljunggren, Karl-Johan Malmberg
Purpose: To evaluate the safety, efficacy, and immunobiological correlates of allogeneic NK-cell-based therapy in primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and de novo AML patients. Experimental Design: Sixteen patients received fludarabine/cyclophosphamide conditioning combined with total lymphoid irradiation followed by adoptive immunotherapy with IL2-activated haploidentical NK cells. Results: NK-cell infusions were well-tolerated, with only transient adverse events observed in the 16 patients...
April 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29439554/pilot-study-on-mass-spectrometry-based-analysis-of-the-proteome-of-cd34%C3%A2-%C2%BAcd123%C3%A2-%C2%BA-progenitor-cells-for-the-identification-of-potential-targets-for-immunotherapy-in-acute-myeloid-leukemia
#12
Johannes R Schmidt, Elke Rücker-Braun, Katharina Heidrich, Malte von Bonin, Friedrich Stölzel, Christian Thiede, Jan M Middeke, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig, Kristin Schubert, Martin von Bergen, Falk Heidenreich
Targeting of leukemic stem cells with specific immunotherapy would be an ideal approach for the treatment of myeloid malignancies, but suitable epitopes are unknown. The comparative proteome-level characterization of hematopoietic stem and progenitor cells from healthy stem cell donors and patients with acute myeloid leukemia has the potential to reveal differentially expressed proteins which can be used as surface-markers or as proxies for affected molecular pathways. We employed mass spectrometry methods to analyze the proteome of the cytosolic and the membrane fraction of CD34 and CD123 co-expressing FACS-sorted leukemic progenitors from five patients with acute myeloid leukemia...
February 12, 2018: Proteomes
https://www.readbyqxmd.com/read/29429903/increased-infiltration-of-cd11-c-cd123-dendritic-cell-subsets-and-upregulation-of-tlr-ifn-%C3%AE-signaling-participate-in-pathogenesis-of-oral-lichen-planus
#13
Yufeng Wang, Shu Shang, Qianqian Sun, Junjun Chen, Guanhuan Du, Hong Nie, Xiaozhe Han, Guoyao Tang
OBJECTIVE: Investigation of dendritic cell (DC) subsets and expression patterns of Toll-like receptors (TLRs) was conducted to understand the pathogenesis in oral lichen planus (OLP). STUDY DESIGN: Blood, OLP lesion, and control samples were collected. Four DC subsets (CD11c+ CD123- myeloid DC1 [mDC1], CD141+ mDC2, CD11c- CD123+ plasmacytoid DC [pDC], and CD1a+ CD207+ Langerhans cells [LC]) were investigated via flow cytometry (FCM) and immunohistochemical staining...
December 18, 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/29424411/-blastic-plasmacytoid-dendritic-cell-neoplasm-report-of-three-cases
#14
Alejandro Avilés-Salas, Myrna Candelaria, Mayra Ponce, Abraham Cañavera-Constantino, Sebastián Burgos
Blastic plasmacytoid dendritic cell neoplasm is a rare hematological malignancy derived from immature plasmacytoid dendritic cells. The tumor cells have an immature blastic appearance, and diagnosis is based on the expression of CD4, CD56 y CD123 in the absence of other lymphoid, natural killer, or myeloid antigens. The majority of affected individuals are older people with a mean age of 66 years. Male to female ratio is approximately 3:1. Common presentation includes cutaneous lesions followed by tumor dissemination...
September 2017: Revista Médica de Chile
https://www.readbyqxmd.com/read/29415975/detection-of-minimal-bone-marrow-involvement-of-blastic-plasmacytoid-dendritic-cell-neoplastic-cells-cd303-immunostaining-as-a-diagnostic-tool
#15
Rintaro Ohe, Naing Ye Aung, Yosuke Shiono, Aya Utsunomiya, Takanobu Kabasawa, Nobuyuki Tamazawa, Yuka Tamura, Tomoya Kato, Akane Yamada, Shin Hasegawa, Keiko Aizawa, Kyoko Inokura, Satoshi Ito, Tomomi Toubai, Yuichi Kato, Takahiko Tsunoda, Kosuke Onami, Tamio Suzuki, Kenichi Ishizawa, Mitsunori Yamakawa
Blastic plasmacytoid dendritic cell (pDC) neoplasm (BPDCN) is a relatively rare hematological malignancy with significantly complex clinicopathological features that are still unclear. This study aimed to analyze the clinicopathological data of BPDCN and evaluate immunohistochemical detection of minimal bone marrow (BM) involvement. In this study, we examined skin and BM lesions from 6 patients with BPDCN. Neoplastic cells tested positive for CD303 (polyclonal, 100%; monoclonal, 40%) in the skin lesions and for CD303 (polyclonal, 100%; monoclonal, 67%) in the BM clots...
March 16, 2018: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/29407181/abnormal-cd25-expression-on-hematopoietic-cells-in-myelodysplastic-syndromes
#16
Pei Liu, Huijuan Jiang, Mengting Che, Rong Fu, Huaquan Wang, Lijuan Li, Wei Zhang, Jinglian Tao, Shan Gao, Zonghong Shao
OBJECTIVE: To investigate the frequencies and biological characteristics of CD25 positive hematopoietic stem cells (HSC) in myelodysplastic syndromes. METHODS: The expression of CD25 on HSC in bone marrow derived from patients with untreated MDS patients, untreated AML patients and normal controls were accessed by flow cytometry (FCM). The correlation analysis was done between CD25+ HSC and clinical parameters in MDS patients. RESULTS: The expression of CD25 on HSC (CD34+ CD38- cells) in MDS patients (28...
April 2018: Leukemia Research
https://www.readbyqxmd.com/read/29398799/evaluating-new-markers-for-minimal-residual-disease-analysis-by-flow-cytometry-in-precursor-b-lymphoblastic-leukemia
#17
Sonal Jain, Anurag Mehta, Gauri Kapoor, Dinesh Bhurani, Sandeep Jain, Narendra Agrawal, Rayaz Ahmed, Dushyant Kumar
Minimal residual disease is currently the most powerful prognostic indicator in Precursor B lymphoblastic leukemia. Multiparameter flow cytometry is the most commonly used modality. Seventy three B ALL cases and 15 normal marrows were evaluated for expression patterns of leukemia markers (CD38, CD58, CD73) in all 73 cases and CD66c, CD86 and CD123 in 23 cases. CD73 was aberrantly expressed in 90.41% cases and CD86 in 60.87% B ALL cases. Thus addition of these markers in MRD panels can increase the sensitivity of the assay...
January 2018: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/29397845/-expressions-of-cd96-and-cd123-and-their-relationship-with-prognosis-of-patients-with-myelodysplastic-syndrome
#18
Xue-Fang Zhang, Shu-Ying Zhang, Hong Zhou, Jia-Wei Feng, Li-Bo Jiang, Yan-Zhang Qu, Heng Guo, Shu-Liang Wang
OBJECTIVE: To explore the relationship between expression of CD96 and CD123 and prognosis of patients with myelodysplastic syndrome(MDS). METHODS: Eight-nine MDS patients(MDS group) and 20 persons without hematologic disease as controls(Control group) were enrolled. The patients were grouped by the risk. All participants received bone marrow biopsy. Mononuclear cells were extracted, CD34+ CD38- CD123+ and CD34+ CD38- CD96+ cells were counted by using flow cytometry...
February 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29396991/alterations-in-natural-killer-and-dendritic-cell-subsets-in-individuals-with-hiv-associated-neurotuberculosis
#19
Deepashri Rao, Manjunatha M Venkataswamy, Ravi Vasanthapuram, Parthasarathy Satishchandra, Anita Desai
One of the commonest HIV-associated opportunistic infections of the central nervous system is neurotuberculosis. Interaction between HIV, Mycobacterium tuberculosis and host immune system in co-infected individuals may result in altered frequencies of immune cells, thereby modulating dissemination and disease progression. We examined the frequencies of natural killer (NK) cell and dendritic cell (DC) subsets in HIV infected individuals with neurotuberculosis (HIVNTB) as compared to individuals with HIV associated systemic TB (HIVSTB), asymptomatic HIV, non-HIV NTB, non-HIV STB, and healthy controls...
May 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29390581/novel-treatment-of-blastic-plasmacytoid-dendritic-cell-neoplasm-a-case-report
#20
Solomiya Grushchak, Cossette Joy, Arielle Gray, Dan Opel, Jodi Speiser, Jeave Reserva, Rebecca Tung, Scott E Smith
RATIONALE: Blastic plasmacytoid dendritic cell neoplasm (BPDCN), derived from precursors of plasmacytoid dendritic cells, is a rare and aggressive malignancy with frequent cutaneous involvement. Although cutaneous lesions are often chemosensitive, BPDCN portends a poor prognosis as most patients relapse after developing drug resistance. PATIENT CONCERNS: We report a case of a 65-year-old man who presented with a rapidly enlarging hyperpigmented plaque on his shoulder with subsequent similarly appearing macules and plaques on his chest, back, and neck...
December 2017: Medicine (Baltimore)
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