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https://www.readbyqxmd.com/read/28636094/characterization-of-clonal-philadelphia-negative-cytogenetic-abnormalities-in-a-large-cohort-of-chronic-myeloid-leukemia
#1
Xiangjun Chen, Jine Zheng, Kaiwei Liang, Yanli He, Wen Du, Juan Li, Wei Liu, Yanjie Hu, Junxia Yao
OBJECTIVES: Clonal Philadelphia-negative Cytogenetic Abnormalities (CPCA) have been reported in chronic myeloid leukaemia (CML) patients treated with either interferon or tyrosine kinase inhibitor (TKI). However, the incidences and types of these cytogenetic abnormalities after treatment vary due to the limited populations enrolled. METHODS: We analysed the frequency and types of CPCA in a cohort of 607 CML patients in the chronic phase after TKI treatment. We also followed up these CPCA with a median of 31...
June 21, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28635660/diverse-regulation-of-vitamin-d-receptor-gene-expression-by-1-25-dihydroxyvitamin-d-and-atra-in-murine-and-human-blood-cells-at-early-stages-of-their-differentiation
#2
Sylwia Janik, Urszula Nowak, Agnieszka Łaszkiewicz, Anastasiia Satyr, Michał Majkowski, Aleksandra Marchwicka, Łukasz Śnieżewski, Klaudia Berkowska, Marian Gabryś, Małgorzata Cebrat, Ewa Marcinkowska
Vitamin D receptor (VDR) is present in multiple blood cells, and the hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) is essential for the proper functioning of the immune system. The role of retinoic acid receptor α (RARα) in hematopoiesis is very important, as the fusion of RARα gene with PML gene initiates acute promyelocytic leukemia where differentiation of the myeloid lineage is blocked, followed by an uncontrolled proliferation of leukemic blasts. RARα takes part in regulation of VDR transcription, and unliganded RARα acts as a transcriptional repressor to VDR gene in acute myeloid leukemia (AML) cells...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28632487/prospective-randomized-comparison-of-idarubicin-and-high-dose-daunorubicin-in-induction-chemotherapy-for-newly-diagnosed-acute-myeloid-leukemia
#3
Je-Hwan Lee, Hawk Kim, Young-Don Joo, Won-Sik Lee, Sung Hwa Bae, Dae Young Zang, Jihyun Kwon, Min Kyoung Kim, Junglim Lee, Gyeong Won Lee, Jung-Hee Lee, Yunsuk Choi, Dae-Young Kim, Eun-Hye Hur, Sung-Nam Lim, Sang-Min Lee, Hun Mo Ryoo, Hyo Jung Kim, Myung Soo Hyun, Kyoo-Hyung Lee
Purpose We compared two induction regimens, idarubicin (12 mg/m(2)/d for 3 days) versus high-dose daunorubicin (90 mg/m(2)/d for 3 days), in young adults with newly diagnosed acute myeloid leukemia (AML). Patients and Methods A total of 299 patients (149 randomly assigned to cytarabine plus idarubicin [AI] and 150 assigned to cytarabine plus high-dose daunorubicin [AD]) were analyzed. All patients received cytarabine (200 mg/m(2)/d for 7 days). Results Complete remission (CR) was induced in 232 patients (77...
June 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28631944/clinical-significance-of-repeat-blood-cultures-during-febrile-neutropenia-in-adult-acute-myeloid-leukaemia-patients-undergoing-intensive-chemotherapy
#4
Shun-Ichi Kimura, Ayumi Gomyo, Jin Hayakawa, Masaharu Tamaki, Yu Akahoshi, Naonori Harada, Tomotaka Ugai, Machiko Kusuda, Kazuaki Kameda, Hidenori Wada, Yuko Ishihara, Koji Kawamura, Kana Sakamoto, Miki Sato, Kiriko Terasako-Saito, Misato Kikuchi, Hideki Nakasone, Shinichi Kako, Aki Tanihara, Yoshinobu Kanda
BACKGROUND: We evaluated the clinical significance of repeat blood cultures in persistent and recurrent fever during neutropenia in adult acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients undergoing intensive chemotherapy. METHODS: We retrospectively reviewed the chemotherapy cycles at our centre between January 2007 and December 2015. Blood cultures obtained within three days after initial febrile neutropenia (FN) were defined as initial blood cultures and those obtained on or after day 4 were defined as repeat blood cultures...
June 20, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28631213/the-constitutive-protease-release-by-primary-human-acute-myeloid-leukemia-cells
#5
Maria Honnemyr, Øystein Bruserud, Annette K Brenner
INTRODUCTION: Acute myeloid leukemia (AML) cells show constitutive release of matrix metalloproteases and their inhibitors. We now investigated this constitutive release of protease/protease regulators associated with carcinogenesis (ADAM12, uPA, cystatin B), angiogenesis (serpin E1, uPA, CD147), cancer cell migration (uPA, cystatin C), coagulation (ADAM TS13, serpin C1), inflammation (fetuin A, caspase 1, cystatin C), monocytic differentiation (CFD) or regulation of hematopoiesis (neutrophil elastase)...
June 19, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28631179/population-pharmacokinetics-of-volasertib-administered-in-patients-with-acute-myeloid-leukaemia-as-a-single-agent-or-in-combination-with-cytarabine
#6
Belén P Solans, Angèle Fleury, Matthias Freiwald, Holger Fritsch, Karin Haug, Iñaki F Trocóniz
BACKGROUND: Volasertib, a potent and selective polo-like kinase inhibitor, has shown to increase response rates and improve survival with a clinically manageable safety profile, administered alone and in combination with cytarabine in patients with acute myeloid leukaemia. OBJECTIVES: The objectives of this analysis were to describe the pharmacokinetics of volasertib and cytarabine, administered as single agents or in combination. METHODS: Three thousand, six hundred and six plasma volasertib concentrations from 501 patients receiving either volasertib alone, or in combination with cytarabine, and 826 plasma cytarabine concentrations from 650 patients receiving cytarabine as multiple subcutaneous injections per cycle either alone, or in combination with volasertib, were analysed using NONMEM Version 7...
June 19, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28630438/the-molecular-pathogenesis-of-the-nup98-hoxa9-fusion-protein-in-acute-myeloid-leukemia
#7
A Rio-Machin, G Gomez-Lopez, J Muñoz, F Garcia-Martinez, A Maiques-Diaz, S Alvarez, R N Salgado, M Shrestha, R Torres, C Haferlach, M J Larrayoz, M J Calasanz, J Fitzgibbon, J C Cigudosa
Leukemia accepted article preview online, 20 June 2017. doi:10.1038/leu.2017.194.
June 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28630119/gata2-haploinsufficiency-accelerates-evi1-driven-leukemogenesis
#8
Saori Katayama, Mikiko Suzuki, Ayaka Yamaoka, Nadine Keleku-Lukwete, Fumiki Katsuoka, Akihito Otsuki, Shigeo Kure, James Douglas Engel, Masayuki Yamamoto
Chromosomal rearrangements between 3q21 and 3q26 induce inappropriate EVI1 expression by recruiting a GATA2-distal hematopoietic enhancer (G2DHE) to the proximity of the EVI1 gene, leading to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The acquisition of G2DHE by the EVI1 gene reciprocally deprives this enhancer of one of the two GATA2 alleles, resulting in a loss of function genetic reduction in GATA2 abundance. As GATA2 haploinsufficiency is strongly associated with MDS and AML, here we asked whether EVI1 misexpression and GATA2 haploinsufficiency both contributed to the observed leukemogenesis by using a 3q21q26 mouse model that recapitulates the G2DHE-driven EVI1 misexpression but in this case coupled to a Gata2 heterozygous germ-line deletion...
June 19, 2017: Blood
https://www.readbyqxmd.com/read/28629373/blimp-1-impairs-t-cell-function-via-upregulation-of-tigit-and-pd-1-in-patients-with-acute-myeloid-leukemia
#9
Liuluan Zhu, Yaxian Kong, Jianhong Zhang, David F Claxton, W Christopher Ehmann, Witold B Rybka, Neil D Palmisiano, Ming Wang, Bei Jia, Michael Bayerl, Todd D Schell, Raymond J Hohl, Hui Zeng, Hong Zheng
BACKGROUND: T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and programmed cell death protein 1 (PD-1) are important inhibitory receptors that associate with T cell exhaustion in acute myeloid leukemia (AML). In this study, we aimed to determine the underlying transcriptional mechanisms regulating these inhibitory pathways. Specifically, we investigated the role of transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1) in T cell response and transcriptional regulation of TIGIT and PD-1 in AML...
June 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28629311/cell-cycle-arrest-and-apoptosis-induction-activity-of-nitidine-chloride-on-acute-myeloid-leukemia-cells
#10
Peng Li, Shuxin Yan, Xin Dong, Zhao Li, Yu Qiu, Chunyan Ji, Jingru Zhang, Min Ji, Wei Li, Hongchun Wang, Zhi Liu, Xing Li Wang, Jingjing Ye, Daoxin Ma
: Background: Acute myeloid leukemia (AML) is the most common hematological malignancy in adults, characterized by distorted proliferation and development of myeloid cells and their precursors in the bone marrow. Nitidine chloride, a naturally occurring alkaloid, has been identified to possess antitumor activity. However, the effects of nitidine chloride on acute myeloid leukemia cells and its underlying mechanisms have not been elucidated. Here we investigated the cellular and molecular mechanism of the anti-leukemic effects of nitidine chloride...
June 19, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28628276/acute-myeloid-leukaemia-relapsing-after-allogeneic-haematopoietic-stem-cell-transplantation-prognostic-factors-and-impact-of-initial-therapy-of-relapse
#11
Andrew B M Lim, Cameron Curley, Chun Yew Fong, Ian Bilmon, Ashanka Beligaswatte, Duncan Purtill, Bartlomiej Getta, Anne Maree Johnston, Tasman Armytage, Marnie Collins, Kate Mason, Katherine Fielding, Matthew Greenwood, John Gibson, Mark Hertzberg, Matthew Wright, Ian Lewis, John Moore, David Curtis, Jeff Szer, Glen Kennedy, David Ritchie
AIMS: We sought to determine factors associated with overall survival from relapse (OSR) of acute myeloid leukaemia (AML) after allogeneic haematopoietic stem cell transplantation (alloHSCT), and the effect of first salvage therapy and subsequent GVHD on OSR. METHODS: Data on 386 patients from nine Australian centres with relapsed AML post-alloHSCT were collected retrospectively. OSR was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the logrank test and proportional hazards modelling respectively, and a prognostic index for OSR was derived from multivariate modelling...
June 19, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28627830/flt3-itd-mutations-in-egyptian-patients-of-acute-myeloid-leukemia-correlation-with-cytogenetic-fab-subgroups-and-prognosis
#12
Shady Adnan-Awad, Ola Gaber, Soad A Eltokhy, Dalia Mourad, Mariam Amer, Eman Z Kandeel, Ihab Eldesouky
BACKGROUND: FLT3-ITD mutations are common in AML subgroups, particularly in Acute Promyelocytic Leukemia (APL). It infers poor prognosis in AML patients; however, its prognostic value in APL is still controversial. We aimed to assess the distribution and prognostic value of FLT3-ITD mutation within AML subgroups, focusing on APL. METHODS: In NCI, Cairo University, 346 newly diagnosed AML patients were included. Morphological, immunophenotypic and cytogenetic analysis were done at presentation and fixed follow-up points with monitoring in follow up visits of patients...
May 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28627644/5%C3%A2-aza%C3%A2-2-%C3%A2-deoxycytidine-promotes-migration-of-acute-monocytic-leukemia-cells-via-activation-of-ccl2%C3%A2-ccr2%C3%A2-erk-signaling-pathway
#13
Xia Xiao, Qian Xu, Yan Sun, Ziwei Lu, Rui Li, Xinxin Wang, Xin Jiang, Guirong Zhang, Yechen Xiao
5-aza‑2'-deoxycytidine (5-Aza) has been approved for clinical use in the treatment of myelodysplastic syndrome and acute myeloid leukemia (AML). It inhibits cell proliferation and induces cell differentiation by demethylating various genes, including tumor suppressor genes, transcription factors, and genes encoding cell cycle inhibitors. Although it has demonstrated efficacy in the clinic, drug resistance following 5‑Aza treatment occurs. Cell migration and invasion following 5‑Aza treatment are considered to be the key factors underlying drug resistance; however, there is currently limited information regarding the detailed mechanisms involved...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627610/silencing-dek-downregulates-cervical-cancer-tumorigenesis-and-metastasis-via-the-dek-p-ser9-gsk-3%C3%AE-p-tyr216-gsk-3%C3%AE-%C3%AE-catenin-axis
#14
Xiaoyang Xu, Lin Zou, Qiuhui Yao, Yanbo Zhang, Li Gan, Liangdan Tang
Cervical cancer is the second most common gynecological malignancy. The mechanisms of the genesis and progression of cervical cancer are complicated and not thoroughly understood. DEK is reported as an oncogene in various cancers, such as acute myeloid leukemia, bladder cancer, breast cancer and hepatocellular cancer. However, its role in cervical cancer has not been well studied. In our study, we confirmed the DEK protein as an oncoprotein in cervical cancer tissues which is correlated to cervical cancer FIGO staging and tumor type...
June 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28627396/prostate-mass-as-a-first-manifestation-of-myeloid-sarcoma-in-a-patient-with-an-occult-acute-myeloid-leukemia-a-case-report
#15
Natally Horvat, Pedro Sergio Brito Panizza, Frederico Perego Costa, Publio Cesar Cavalcanti Viana
Myeloid sarcoma (MS) with either primary or secondary prostate involvement is extremely rare. Its diagnostic is particularly challenging when prostate lesion precedes the systemic manifestation of a myeloproliferative disorder. We report such a case in a 44-year-old man with a prostate mass as a first manifestation of myeloid sarcoma associated with acute myeloid leukemia (AML). The diagnosis of lymphoproliferative disorder was suspected in the prostate magnetic resonance imaging (MRI) and MS was confirmed after transrectal ultrasound-guided prostate core biopsy...
June 13, 2017: Urology
https://www.readbyqxmd.com/read/28627035/detection-of-the-hla-dqb1-allele-dqb1-03-82-in-a-kazakh-patient-with-acute-myeloid-leukemia
#16
Z K Burkitbayev, S A Abdrakhmanova, A A Turganbekova, I R Ramilyeva, D K Baimukasheva
HLA-DQB1*03:82 differs from DQB1*03:01 at nucleotide 223 in exon 2 from G to A.
June 19, 2017: HLA
https://www.readbyqxmd.com/read/28626802/cohesin-mutations-in-myeloid-malignancies
#17
Joseph B Fisher, Maureen McNulty, Michael J Burke, John D Crispino, Sridhar Rao
Acute Myeloid Leukemia (AML) is a hematologic malignancy with a poor prognosis. Recent genome-wide sequencing studies have identified frequent mutations in genes encoding members of the cohesin complex. Mutations in cohesin contribute to myeloid malignancies by conferring enhanced self-renewal of hematopoietic stem and progenitor cells but the mechanisms behind this phenotype have not been fully elucidated. Of note, cohesin mutations are highly prevalent in acute megakaryocytic leukemia associated with Down syndrome (DS-AMKL), where they occur in over half of patients...
April 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28626542/invasive-aspergillosis-with-disseminated-skin-involvement-in-a-patient-with-acute-myeloid-leukemia-a-rare-case
#18
Duygu Mert, Gülşen Iskender, Fazilet Duygu, Alparslan Merdin, Sinan Dal Mehmet, Mehmet Dogan, Emre Tekgündüz, Mustafa Ertek, Fevzi Altuntaş
Invasive pulmonary aspergillosis is most commonly seen in immunocompromised patients. Besides, skin lesions may also develop due to invasive aspergillosis in those patients. A 49-year-old male patient was diagnosed with acute myeloid leukemia. The patient developed bullous and zosteriform lesions on the skin after the 21st day of hospitalization. The skin biopsy showed hyphae. Disseminated skin aspergillosis was diagnosed to the patient. Voricanazole treatment was initiated. The patient was discharged once the lesions started to disappear...
June 1, 2017: Hematology Reports
https://www.readbyqxmd.com/read/28626381/nilotinib-induced-acute-pancreatitis-in-a-patient-with-chronic-myeloid-leukemia
#19
Vihang Patel, Anil Pattisapu, Karim Attia, John Weiss
Nilotinib, a second-generation tyrosine kinase inhibitor, is used for treatment of chronic myeloid leukemia (CML); it has been widely used especially for imatinib-resistant CML. Despite being a novel drug in this therapeutic class, it has the potential to be harmful. We present the case of an elderly woman who developed life-threatening acute pancreatitis as an adverse event after having started the drug. There is only one reported case in the literature of nilotinib-induced acute pancreatitis. The purpose of this case report is to educate physicians who prescribe this medication to be aware of potential life-threatening adverse events...
May 2017: Case Reports in Gastroenterology
https://www.readbyqxmd.com/read/28625976/a-genome-wide-crispr-screen-identifies-genes-critical-for-resistance-to-flt3-inhibitor-ac220
#20
Panpan Hou, Chao Wu, Yuchen Wang, Rui Qi, Dheeraj Bhavanasi, Zhixiang Zuo, Cedric Dos Santos, Shuliang Chen, Yu Chen, Hong Zheng, Hong Wang, Alexander E Perl, Deyin Guo, Jian Huang
Acute myeloid leukemia (AML) is a malignant hematopoietic disease and the most common type of acute leukemia in adults. The mechanisms underlying drug resistance in AML are poorly understood. Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are the most common molecular abnormality in AML. Quizartinib (AC220) is a potent and selective second-generation inhibitor of FLT3. It is in clinical trials for the treatment of relapsed or refractory FLT3-ITD-positive and -negative AML patients and as maintenance therapy...
June 16, 2017: Cancer Research
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