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Chronic granulocytic leukemia

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https://www.readbyqxmd.com/read/29296875/vaccination-with-autologous-myeloblasts-admixed-with-gm-k562-cells-in-patients-with-advanced-mds-or-aml-after-allogeneic-hsct
#1
Vincent T Ho, Haesook T Kim, Natalie Bavli, Martin Mihm, Olga Pozdnyakova, Matthias Piesche, Heather Daley, Carol Reynolds, Nicholas C Souders, Corey Cutler, John Koreth, Edwin P Alyea, Joseph H Antin, Jerome Ritz, Glenn Dranoff, Robert J Soiffer
We report a clinical trial testing vaccination of autologous myeloblasts admixed with granulocyte-macrophage colony-stimulating factor secreting K562 cells after allogeneic hematopoietic stem cell transplantation (HSCT). Patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with ≥5% marrow blasts underwent myeloblast collection before HSCT. At approximately day +30, 6 vaccines composed of irradiated autologous myeloblasts mixed with GM-K562 were administered. Tacrolimus-based graft-versus-host disease (GVHD) prophylaxis was not tapered until vaccine completion (∼day 100)...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29228732/hoxa9-and-hoxa10-induce-cml-myeloid-blast-crisis-development-through-activation-of-myb-expression
#2
Vijay Negi, Bandana A Vishwakarma, Su Chu, Kevin Oakley, Yufen Han, Ravi Bhatia, Yang Du
Mechanisms underlying the progression of Chronic Myeloid Leukemia (CML) from chronic phase to myeloid blast crisis are poorly understood. Our previous studies have suggested that overexpression of SETBP1 can drive this progression by conferring unlimited self-renewal capability to granulocyte macrophage progenitors (GMPs). Here we show that overexpression of Hoxa9 or Hoxa10, both transcriptional targets of Setbp1, is also sufficient to induce self-renewal of primary myeloid progenitors, causing their immortalization in culture...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29226717/atypical-chronic-myeloid-leukemia-a-rare-entity-with-management-challenges
#3
Prajwal Dhakal, Krishna Gundabolu, Catalina Amador, Supratik Rayamajhi, Vijaya Raj Bhatt
The aim of our study was to review the clinicopathologic features and management of atypical chronic myeloid leukemia (aCML). Relevant manuscripts published in English were searched using PubMed. aCML is diagnosed as per WHO 2016 classification in the presence of leukocytosis ≥13 × 109/l with circulating neutrophil precursors ≥10%, monocytes less than 10%, minimal basophils, hypercellular bone marrow with granulocytic proliferation and dysplasia, bone marrow blast less than 20% and absence of BCR/ABL fusion gene...
December 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/29107664/eruption-of-lymphocyte-recovery-with-atypical-lymphocytes-mimicking-a-primary-cutaneous-t-cell-lymphoma-a-series-of-12-patients
#4
Charlotte Hurabielle, Emilie Sbidian, Helmut Beltraminelli, Brigitte Bouchindhomme, Catherine Chassagne-Clément, Brigitte Balme, Céline Bossard, Marie-Hélène Delfau-Larue, Pierre Wolkenstein, Olivier Chosidow, Catherine Cordonnier, Andrea Toma, Cécile Pautas, Nicolas Ortonne
Eruption of lymphocyte recovery (ELR) may occur during bone marrow aplasia after chemotherapies. We reviewed the clinical and pathologic features of 12 patients (male/female: 7/5, median age: 61years) with an atypical ELR histologically mimicking a primary cutaneous T-cell lymphoma (CTCL) such as Sézary Syndrome or CD30+ T-cell lymphoproliferative disorder (LPD). All the patients displayed an erythematous maculopapular eruption on the trunk and the limbs, associated with fever. All but one had received a polychemotherapy for an acute myeloid leukemia (n=10) or an urothelial carcinoma (n=1) before the occurrence of the skin eruption...
October 28, 2017: Human Pathology
https://www.readbyqxmd.com/read/28972490/phagocytosis-and-expression-of-fcg-receptors-and-cd180-on-monocytes-in-chronic-lymphocytic-leukemia
#5
T Tsertsvadze, N Mitskevich, A Bilanishvili, D Girdaladze, N Porakishvili
Chronic lymphocytic leukaemia (CLL) is a lymphoproliferative disease characterised by accumulation of monoclonal CD19+CD5+CD23+ lymphocytes in the peripheral blood and bone marrow. CLL is the most common type of the adult leukemia in the Western world. The disease is incurable, albeit there are new molecular and immunotherapy methods currently available in conjunction with chemotherapy, leading to the "precision therapy". The majority of immunotherapeutic approaches are based on the ability of therapeutic antibodies (Rituximab, Alemtuzumab) to mobilize anti-tumour potential of the Natural Killer cells and macrophages/monocytes through their Fcg-receptors (FcγR)...
September 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28927137/atypical-chronic-myeloid-leukemia-with-isochromosome-x-p10-a-case-report
#6
Masahide Yamamoto, Sayaka Suzuki, Jun-Ichi Mukae, Keisuke Tanaka, Ken Watanabe, Gaku Oshikawa, Tetsuya Fukuda, Naomi Murakami, Osamu Miura
Atypical chronic myeloid leukemia (aCML) is a rare subtype of myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Although recurrent chromosomal and genetic abnormalities are frequently observed in aCML, none are specific to this type of leukemia. The present study reported a case of aCML associated with i(X)(p10), a rare recurrent chromosomal abnormality of hematological malignancy. A 40-year-old female was referred to the Tokyo Medical and Dental University Hospital (Tokyo, Japan) due to slight leukocytosis and anemia...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28919910/chloroma-of-the-testis-in-a-patient-with-a-history-of-acute-myeloid-leukemia
#7
Mohammad Hossein Sanei, Matin Shariati
Chloroma, or granulocytic sarcoma, is a rare extramedullary solid hematologic cancer, found concomitant with acute myeloid leukemia. It is infrequently associated with other myeloproliferative disorders or chronic myelogenous leukemia. Chloroma of the testis after allogeneic bone marrow transplantation is particularly sparsely represented in the literature. It is suggested that an appropriate panel of marker studies be performed along with clinical correlation and circumspection to avoid misleading conclusions...
2017: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/28881589/decreased-calpain-activity-in-chronic-myeloid-leukemia-impairs-apoptosis-by-increasing-survivin-in-myeloid-progenitors-and-xiap1-in-differentiating-granulocytes
#8
Weiqi Huang, Ling Bei, Elizabeth E Hjort, Elizabeth A Eklund
Chronic Myeloid Leukemia (CML) is characterized by translocations between chromosomes 9 and 22, resulting in expression of Bcr-abl oncogenes. Although the clinical course of CML was revolutionized by development of Bcr-abl-directed tyrosine kinase inhibitors (TKIs), CML is not cured by these agents. Specifically, the majority of subjects relapsed in clinical trials attempting TKI discontinuation, suggesting persistence of leukemia stem cells (LSCs) even in molecular remission. Identifying mechanisms of CML-LSC persistence may suggest rationale therapeutic targets to augment TKI efficacy and lead to cure...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28828991/a-virtual-screening-approach-for-the-identification-of-high-affinity-small-molecules-targeting-bcr-abl1-inhibitors-for-the-treatment-of-chronic-myeloid-leukemia
#9
Saphy Sharda, Palash Sarmandal, Shirisha Cherukommu, Kiran Dindhoria, Manisha Yadav, Srinivas Bandaru, Anudeep Sharma, Aditi Sakhi, Tanmay Vyas, Tajamul Hussain, Anuraj Nayarisseri, Sanjeev Kumar Singh
CML originates due to reciprocal translocation in Philadelphia chromosome leading to the formation of fusion product BCR-ABL which constitutively activates tyrosine kinase signaling pathways eventually leading to abnormal proliferation of granulocytic cells. As a therapeutic strategy, BCR-ABL inhibitors have been clinically approved which terminates its phosphorylation activity and retards cancer progression. However, a number of patients develop resistance to inhibitors which demand for the discovery of new inhibitors...
2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28812528/acute-leukemia-in-horses
#10
Carina J Cooper, Stefan M Keller, Luis G Arroyo, Joanne Hewson, Daniel Kenney, Dorothee Bienzle
Leukemia is broadly divided into acute and chronic lymphocytic and myeloid types based on the proportion of blasts, morphology of cells, and expression of specific antigens on neoplastic cells. Classifying leukemia in horses can be challenging if blasts predominate and since few antibodies to identify cell types are available. The objective of this study was to describe in detail the clinical and pathologic features of acute leukemia in horses. Twelve horses ranging from 0.2 to 25.9 years of age were diagnosed with acute leukemia...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28694526/intrapatient-functional-clonality-deconvoluted-by-coupling-intracellular-flow-cytometry-and-next-generation-sequencing-in-human-leukemia
#11
Q Zhang, M C Ball, Y Zhao, M Balasis, C Letson, A Vedder, A F List, P K Epling-Burnette, R S Komrokji, E Padron
The interplay between tumor heterogeneity and microenvironmental factors is a critical mechanism for clonal selection in leukemia. Evidence of unique clonal capacities to engraft within patient-derived xenograft (PDX) models suggests that intrapatient genetic architecture may be defined by functional differences at the clonal level. However, methods to detect functional differences assigned to genetically defined clones remain limited. Here, we describe a scalable method to directly measure the functional properties of clones within the same leukemia patient by coupling intracellular flow cytometry and next-generation sequencing (NGS)...
June 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28676100/superior-gvhd-free-relapse-free-survival-for-g-bm-to-g-pbsc-grafts-is-associated-with-higher-mdscs-content-in-allografting-for-patients-with-acute-leukemia
#12
Qian Fan, Hui Liu, Xinquan Liang, Ting Yang, Zhiping Fan, Fen Huang, Yiwen Ling, Xin Liao, Li Xuan, Na Xu, Xiaojun Xu, Jieyu Ye, Qifa Liu
BACKGROUND: Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (G-PBSC) has largely replaced unstimulated bone marrow (un-BM) for allografting because of accelerated engraftment, but with a higher morbidity and mortality of graft-versus-host-disease (GVHD). Recent studies suggested that G-CSF-primed BM (G-BM) had similar engraftment but lower morbidity and mortality of GVHD comparing to G-PBSC. A prospective, randomized, multicenter study was conducted to compare G-BM with G-PBSC as the grafts in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia in first complete remission (CR1)...
July 4, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28652245/unpaired-extracellular-cysteine-mutations-of-csf3r-mediate-gain-or-loss-of-function
#13
Haijiao Zhang, Sophie Means, Anna Reister Schultz, Kevin Watanabe-Smith, Bruno C Medeiros, Daniel Bottomly, Beth Wilmot, Shannon K McWeeney, Tim Kükenshöner, Oliver Hantschel, Jeffrey W Tyner
Exclusive of membrane-proximal mutations seen commonly in chronic neutrophilic leukemia (e.g., T618I), functionally defective mutations in the extracellular domain of the G-CSF receptor (CSF3R) have been reported only in severe congenital and idiopathic neutropenia patients. Here, we describe the first activating mutation in the fibronectin-like type III domain of the extracellular region of CSF3R (W341C) in a leukemia patient. This mutation transformed cells via cysteine-mediated intermolecular disulfide bonds, leading to receptor dimerization...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28572287/how-i-treat-chronic-myelomonocytic-leukemia
#14
REVIEW
Eric Solary, Raphael Itzykson
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy that may deserve specific management. Defined by a persistent peripheral blood monocytosis ≥1 × 109/L and monocytes accounting for ≥10% of the white blood cells, this aging-associated disease combines cell proliferation as a consequence of myeloid progenitor hypersensitivity to granulocyte-macrophage colony-stimulating factor with myeloid cell dysplasia and ineffective hematopoiesis. The only curative option for CMML remains allogeneic stem cell transplantation...
July 13, 2017: Blood
https://www.readbyqxmd.com/read/28533818/a-novel-bcr-abl1-fusion-gene-with-genetic-heterogeneity-indicates-a-good-prognosis-in-a-chronic-myeloid-leukemia-case
#15
Fen Zhou, Runming Jin, Yu Hu, Heng Mei
BACKGROUND: Chronic myelogenous leukemia (CML) is a pluripotent hematopoietic stem cell disorder caused by the fusion of the BCR and ABL1 genes. Quantitative RT-PCR (qRT-PCR) is a routinely performed screening technique to identify BCR-ABL1 fusion genes, but a limitation of this method is its inability to recognize novel fusions that have not been previously characterized. Next-generation sequencing (NGS) is an effective and sensitive detection method for the determination of novel BCR-ABL1 fusion genes as well as previously characterized ones...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28499936/umbilical-cord-blood-transplantation-without-antithymocyte-globulin-results-in-similar-survival-but-better-quality-of-life-compared-with-unrelated-peripheral-blood-stem-cell-transplantation-for-the-treatment-of-acute-leukemia-a-retrospective-study-in-china
#16
Juan Tong, Li Xuan, Yanling Sun, Dongping Huang, Huilan Liu, Changcheng Zheng, Xiaoyu Zhu, Baolin Tang, Kaidi Song, Xuhan Zhang, Lei Zhang, Wen Yao, Dongjun Lin, Qifa Liu, Zimin Sun
Although previous studies have demonstrated improved outcomes in umbilical cord blood transplantation (UCBT) by omitting antithymocyte globulin (ATG) in the conditioning regimen, this approach has not been comparatively studied in unrelated peripheral blood stem cell transplantation (UPBSCT). To compare the risks and benefits between UCBT without ATG and UPBSCT in patients with acute leukemia (AL), we conducted a multicenter retrospective study of 79 patients who underwent UCBT (myeloablative conditioning without ATG) and 96 patients who underwent UPBSCT (myeloablative conditioning with ATG)...
September 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28431398/decreased-calpain-activity-in-chronic-myeloid-leukemia-impairs-apoptosis-by-increasing-survivin-in-myeloid-progenitors-and-xiap1-in-differentiating-granulocytes
#17
Weiqi Huang, Ling Bei, Elizabeth E Hjort, Elizabeth A Eklund
Chronic Myeloid Leukemia (CML) is characterized by translocations between chromosomes 9 and 22, resulting in expression of Bcr-abl oncogenes. Although the clinical course of CML was revolutionized by development of Bcr-abl-directed tyrosine kinase inhibitors (TKIs), CML is not cured by these agents. Specifically, the majority of subjects relapsed in clinical trials attempting TKI discontinuation, suggesting persistence of leukemia stem cells (LSCs) even in molecular remission. Identifying mechanisms of CML-LSC persistence may suggest rationale therapeutic targets to augment TKI efficacy and lead to cure...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423730/the-sclttaxbcr-abl-transgenic-mouse-model-closely-reflects-the-differential-effects-of-dasatinib-on-normal-and-malignant-hematopoiesis-in-chronic-phase-cml-patients
#18
Claudia Schubert, Nicolas Chatain, Till Braunschweig, Mirle Schemionek, Kristina Feldberg, Melanie Hoffmann, Olli Dufva, Satu Mustjoki, Tim H Brümmendorf, Steffen Koschmieder
The second generation tyrosine kinase inhibitor (TKI) dasatinib is a clinically approved drug for chronic myeloid leukemia (CML) as well as Ph+ acute lymphoblastic leukemia. In addition to its antileukemic effects, dasatinib was shown to impact on normal hematopoiesis and cells of the immune system.Due to the fact that the murine in vivo studies so far have not been performed in a chronic-phase CML model under steady-state conditions, our aim was to study the hematopoietic effects of dasatinib (20 mg/kg p.o...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28314085/targeted-next-generation-sequencing-and-identification-of-risk-factors-in-world-health-organization-defined-atypical-chronic-myeloid-leukemia
#19
Mrinal M Patnaik, Daniela Barraco, Terra L Lasho, Christy M Finke, Kaaren Reichard, Katherine P Hoversten, Rhett P Ketterling, Naseema Gangat, Ayalew Tefferi
Atypical chronic myeloid leukemia (aCML) is an aggressive myeloid neoplasm with overlapping features of myelodysplastic syndromes (prominent granulocytic dysplasia) and myeloproliferative neoplasms (neutrophilic leukocytosis). We studied 25 molecularly-annotated and World Health Organization defined aCML patients; median age 70 years, 84% males. Cytogenetic abnormalities were seen in 36% and gene mutations in 100%. Mutational frequencies were, ASXL1 28%, TET2 16%, NRAS 16%, SETBP1 12%, RUNX1 12%, ETNK1 8%, and PTPN11 4%...
June 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28287132/crispr-cas9-generated-p47-phox-deficient-cell-line-for-chronic-granulomatous-disease-gene-therapy-vector-development
#20
Dominik Wrona, Ulrich Siler, Janine Reichenbach
Development of gene therapy vectors requires cellular models reflecting the genetic background of a disease thus allowing for robust preclinical vector testing. For human p47(phox)-deficient chronic granulomatous disease (CGD) vector testing we generated a cellular model using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 to introduce a GT-dinucleotide deletion (ΔGT) mutation in p47(phox) encoding NCF1 gene in the human acute myeloid leukemia PLB-985 cell line. CGD is a group of hereditary immunodeficiencies characterized by impaired respiratory burst activity in phagocytes due to a defective phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase...
March 13, 2017: Scientific Reports
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