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Leukemia Research

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https://www.readbyqxmd.com/read/28704720/the-dana-farber-consortium-protocol-dfcp-vs-classic-hyper-cvad-for-treatment-of-acute-lymphoblastic-leukemia-in-patients-50-y-single-institution-experience
#1
Amal S Alabdulwahab, Hussein G Elsayed, Mohamed A Sherisher, Ahmed Zeeneldin, Khalofa Alghamdi, Wafaa M Elbjeirami
BACKGROUND: The use of intensive pediatric protocols for the treatment of ALL is being extended to older adults. AIM OF THE STUDY: Analysis of the efficacy and toxicity results of pediatric DFCP vs. classic Hyper-CVAD protocol for the treatment of patients with ALL < 50 Y. PATIENTS AND METHODS: A retrospective single center comparative analysis of DFCP & classic Hyper-CVAD for first line treatment of patients with ALL < 50 Y. RESULTS: 73 patients were included, 43 received DFCP and 30 received Hyper-CVAD protocol...
June 28, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28667884/exome-sequencing-reveals-dnmt3a-and-asxl1-variants-associate-with-progression-of-chronic-myeloid-leukemia-after-tyrosine-kinase-inhibitor-therapy
#2
TaeHyung Kim, Marc S Tyndel, Zhaolei Zhang, Jaesook Ahn, Seunghyun Choi, Michael Szardenings, Jeffrey H Lipton, Hyeoung-Joon Kim, Dennis Kim Dong Hwan
OBJECTIVE: The development of tyrosine kinase inhibitors (TKIs) has significantly improved the treatment of chronic myeloid leukemia (CML). However, approximately one third of patients are resistant to TKI and/or progress to advanced disease stages. TKI therapy failure has a well-known association with ABL1 kinase domain (KD) mutations, but only around half of TKI non-responders have detectable ABL1 KD mutations. METHOD: We attempt to identify genetic markers associated with TKI therapy failure in 13 patients (5 resistant, 8 progressed) without ABL1 KD mutations using whole-exome sequencing...
June 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28651105/heterogeneous-epigenetic-regulation-of-hace1-in-burkitt-lymphoma-derived-cells
#3
Abdelilah Bouzelfen, Hafid Kora, Marion Alcantara, Philippe Bertrand, Jean-Baptiste Latouche, Fabrice Jardin
We examined the consequences of 3-deazaneplanocin A (DZNep) on HACE1 expression in human Burkitt- Lymphoma-derived cells to investigate fundamental molecular mechanisms that control its expression. We treated the human Burkitt- Lymphoma-derived cells lines Ramos and Raji with DZNep and examined HACE1 mRNA expression by RT-PCR. We also studied the effect of DZNep on the methylation of lysine 9 and 27 of histone 3 (H3K27me3 and H3K9me2) associated with the CpG88 and CpG177 islands of the HACE1 promoters by chromatin immunoprecipitation and quantitative PCR...
June 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28651104/autophagy-is-an-important-event-for-low-dose-cytarabine-treatment-in-acute-myeloid-leukemia-cells
#4
Liyun Chen, Pei Guo, Yunxiang Zhang, Xiaoyang Li, Peimin Jia, Jianhua Tong, Junmin Li
Cytarabine (Ara-c) has been an important agent in acute myeloid leukemia (AML) treatment for more than 40 years. While, the mechanisms underlying low dose cytarabine (LD Ara-c) is poorly understood. In this study, we investigated the therapeutic effect of LD Ara-C in vitro. U937 and HEL cell lines were treated with increasing dose of Ara-C and showed growth inhibition rates in a time and dose-dependent manner. Treatment with LD Ara-C (50nM) induced a time-dependent increase in expression of microtubule-associated protein light chain 3 (LC3) and beclin1, but degradation of sequestosome1 (p62) in both U937 and HEL cells...
June 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28648672/prognostic-significance-of-interventricular-septal-thickness-in-patients-with-al-amyloidosis
#5
Hyunsoo Cho, Soo-Jeong Kim, Chi Young Shim, Geu-Ru Hong, Jong-Won Ha, Yu Ri Kim, Woo Ick Yang, Haerim Chung, Ji Eun Jang, June-Won Cheong, Yoo Hong Min, Jin Seok Kim
The major prognostic determinant of immunoglobulin light chain (AL) amyloidosis is cardiac involvement. However, the role of interventricular septal thickness (IVST), which reflects the extent of cardiac involvement, remains unclear. Therefore, we analyzed 77 patients with newly diagnosed AL amyloidosis and evaluated the prognostic role of IVST. Fifty patients (64.9%) had cardiac involvement and 17 patients (22.1%) showed IVST >15mm. Among all patients, the revised Mayo Clinic Stage III-IV and IVST >15mm were independently associated with inferior overall survival (OS) in a multivariable analysis...
June 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28646676/multicenter-phase-2-study-of-combination-therapy-with-ruxolitinib-and-danazol-in-patients-with-myelofibrosis
#6
K Gowin, H Kosiorek, A Dueck, J Mascarenhas, R Hoffman, C Reeder, J Camoriano, R Tibes, K Gano, J Palmer, R Mesa
Myelofibrosis is a myeloproliferative neoplasm that is characterized by splenomegaly, profound symptom burden, and cytopenias. JAK inhibitor therapy offers improvements in splenomegaly, symptom burden, and potentially survival; however, cytopenias remain a significant challenge. Danazol has previously demonstrated improvements in myelofibrosis-associated anemia. We conducted a phase II clinical trial evaluating the efficacy and tolerability of combination therapy with ruxolitinib, an oral JAK inhibitor, and danazol...
June 13, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28622624/primary-myelofibrosis-older-age-and-high-jak2v617f-allele-burden-are-associated-with-elevated-plasma-high-sensitivity-c-reactive-protein-levels-and-a-phenotype-of-progressive-disease
#7
Giovanni Barosi, Margherita Massa, Rita Campanelli, Gabriela Fois, Paolo Catarsi, Gianluca Viarengo, Laura Villani, Valentina Poletto, Tiziana Bosoni, Umberto Magrini, Robert P Gale, Vittorio Rosti
We measured plasma levels of high-sensitivity C-reactive protein (hs-CRP) in 526 subjects with primary myelofibrosis (PMF). Thirty-eight percent had an elevated hs-CRP level (≥0.3mg/dL). Elevated hs-CRP levels were associated with a progressive disease phenotype, including anemia, high white blood cell count, low platelet count, increased splenomegaly, increased risk of blast transformation, and worse survival. Age≥52years, but no other demographic characteristics, was associated with an elevated hs-CRP level in multivariable logistic regression (odds ratio [OR], 4...
June 7, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28641145/lack-of-association-between-deletion-polymorphism-of-bim-gene-and-in-vitro-drug-sensitivity-in-b-cell-precursor-acute-lymphoblastic-leukemia
#8
Meixian Huang, Kunio Miyake, Keiko Kagami, Masako Abe, Tamao Shinohara, Atsushi Watanabe, Shinpei Somazu, Hiroko Oshiro, Kumiko Goi, Hiroaki Goto, Masayoshi Minegishi, Shotaro Iwamoto, Nobutaka Kiyokawa, Kanji Sugita, Takeshi Inukai
A deletion polymorphism in the BIM gene was identified as an intrinsic mechanism for resistance to tyrosine kinase inhibitor in chronic myeloid leukemia patients in East Asia. BIM is also involved in the responses to glucocorticoid and chemotherapy in acute lymphoblastic leukemia (ALL), suggesting a possible association between deletion polymorphism of BIM and the chemosensitivity of ALL. Thus, we analyzed 72 B-cell precursor (BCP)-ALL cell lines established from Japanese patients. Indeed, higher BIM gene expression was associated with good in vitro sensitivities to glucocorticoid and chemotherapeutic agents used in induction therapy...
June 4, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28599191/targeting-autophagy-in-multiple-myeloma
#9
REVIEW
Zhuang Yun, Jin Zhichao, Yao Hao, Ji Ou, Yang Ran, Dong Wen, Shen Qun
Autophagy plays an important role in plasma cell ontogeny and in the pathophysiology of multiple myeloma. Autophagy is usually considered a pro-survival mechanism, and cooperates with the ubiquitin proteasome system in maintaining the homeostasis of myeloma cells by degrading excessive and misfolded proteins for energy recycling. Therefore, the inhibition of autophagy could effectively induce death in myeloma cells, and could synergize with proteasome inhibitors. However, the excessive activation of autophagy could also lead to the extreme degradation of the organelles that induce autophagic cell death...
June 3, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28601551/patients-with-post-essential-thrombocythemia-and-post-polycythemia-vera-differ-from-patients-with-primary-myelofibrosis
#10
Lucia Masarova, Prithviraj Bose, Naval Daver, Naveen Pemmaraju, Kate J Newberry, Taghi Manshouri, Jorge Cortes, Hagop M Kantarjian, Srdan Verstovsek
Prognostic scoring systems for primary myelofibrosis (PMF) are not accurate in patients with post-essential thrombocythemia and post-polycythemia vera myelofibrosis (PET-MF; PPV-MF). Given the paucity of data describing the clinical characteristics, disease course and outcomes of these patients, we sought to describe and compare the clinical characteristics and outcomes of 755 patients with PMF, 181 with PPV-MF, and 163 with PET-MF referred to our institution between 1984 and 2013. The median follow-up was 31 months, and 56% (n=616) patients had died...
June 2, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28654842/haploidentical-hematopoietic-stem-cell-transplantation-for-pediatric-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-in-the-imatinib-era
#11
Huan Chen, Kai-Yan Liu, Lan-Ping Xu, Yu-Hong Chen, Xiao-Hui Zhang, Yu Wang, Ya-Zhen Qin, Yan-Rong Liu, Yue-Yun Lai, Xiao-Jun Huang
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains an important curative option for children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who have a poor response to chemotherapy plus imatinib. For such children, if there are no matched related or unrelated donors, alternative donor transplantation may be a choice. The role of haploidentical donor (HID) HSCT in pediatric patients with Ph+ ALL has not been reported. The study population included pediatric patients with Ph+ ALL who underwent HID-HSCT...
June 1, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28624713/aneuploidy-identification-in-pre-b-acute-lymphoblastic-leukemia-patients-at-diagnosis-by-multiplex-ligation-dependent-probe-amplification-mlpa
#12
A Vázquez-Reyes, L Bobadilla-Morales, C Barba-Barba, G Macías-Salcedo, G Serafín-Saucedo, M E Velázquez-Rivera, M C Almodóvar-Cuevas, A Márquez-Mora, H J Pimentel-Gutiérrez, C Ortega-de-la-Torre, R M Cruz-Osorio, S Nava-Gervasio, J Rivera-Vargas, F Sánchez-Zubieta, J R Corona-Rivera, A Corona-Rivera
Three-quarters of the patients with acute lymphoblastic leukemia (ALL), show numerical or structural chromosomal alterations, which are important factors in leukemogenesis. The use of Multiplex Ligation-dependent Probes Amplification (MLPA) has been mainly limited for searching copy number alterations of genes, suggesting that MLPA could detect numerical alterations in cancer. However, the use of MLPA in pediatrics to analyze subtelomeric sequences for aneuploidy detection has not been considered in previous studies...
June 1, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28618329/therapy-of-older-persons-with-acute-myeloid-leukaemia
#13
REVIEW
Utz Krug, Robert Peter Gale, Wolfgang E Berdel, Carsten Müller-Tidow, Matthias Stelljes, Klaus Metzeler, M Cristina Sauerland, Wolfgang Hiddemann, Thomas Büchner
Most persons age≥60 y with acute myeloid leukaemia (AML) die from their disease. When interpreting clinical trials data from these persons one must be aware of substantial selection biases. Randomized trials of post-remission treatments can be performed upfront or after achieving defined landmarks. Both strategies have important limitations. Selection of the appropriate treatment is critical. Age, performance score, co-morbidities and frailty provide useful data to treatment selection. If an intensive remission induction therapy is appropriate, therapy with cytarabine and an anthracycline is the most common regimen...
June 1, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28599190/sharing-post-aml-consolidation-supportive-therapy-with-local-centers-reduces-patient-travel-burden-without-compromising-outcomes
#14
Samantha A Hershenfeld, Kimberly Maki, Lana Rothfels, Cindy S Murray, Shannon Nixon, Aaron D Schimmer, Mary C Doherty
Acute myeloid leukemia (AML) is frequently treated with induction and consolidation chemotherapy. Consolidation chemotherapy can be delivered on an ambulatory basis, requiring some patients to travel long distances for treatment at specialized centers. We developed a shared care model where patients receive consolidation chemotherapy at a quaternary center, but post-consolidation supportive care at local hospitals. To evaluate the impact of our model on patient travel and outcomes we conducted a retrospective analysis of AML and acute promyelocytic leukemia patients receiving consolidation over four years at our quaternary center...
June 1, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28599188/mast-cell-leukemia-mcl-clinico-pathologic-and-molecular-features-and-survival-outcome
#15
Preetesh Jain, Sa Wang, Keyur P Patel, Nawid Sarwari, Jorge Cortes, Hagop Kantarjian, Srdan Verstovsek
Mast cell leukemia (MCL) is a very rare subtype of systemic mastocytosis (SM). We have identified 13 such patients (5.9%) among 218 patients with SM seen at our institution between 1994 and 2016. Patients with MCL had poor survival (median 31.6 months); response to various therapies was rare and not durable. Clinical course may be affected by concurrent associated hematologic neoplasm and different genetic profiles. More research is required to decipher this rare and enigmatic SM subtype.
June 1, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28582636/living-with-the-burden-of-relapse-in-multiple-myeloma-from-the-patient-and-physician-perspective
#16
Cyrille Hulin, Timon Hansen, Louise Heron, Rachel Pughe, Matthew Streetly, Ananda Plate, Sue Perkins, Kate Morgan, Antoine Tinel, Filipe Rodrigues, Karthik Ramasamy
Multiple myeloma (MM) is a progressive plasma cell malignancy, with a range of clinical features including bone lesions, renal insufficiency, anaemia, and hypercalcaemia. Novel agents have significantly improved patient survival, however most patients will suffer multiple relapses. Although clinical challenges and economic costs of relapse are recognised, the psychological impact of relapse is not fully appreciated. Additionally, there is little information on how physicians perceive the impact of relapse on their patients' emotional state and how this might affect patient management...
May 31, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28622623/a-phase-2-study-of-momelotinib-a-potent-jak1-and-jak2-inhibitor-in-patients-with-polycythemia-vera-or-essential-thrombocythemia
#17
Srdan Verstovsek, Stephane Courby, Martin Griesshammer, Ruben A Mesa, Carrie Baker Brachmann, Jun Kawashima, Julia D Maltzman, Lixin Shao, Yan Xin, Daniel Huang, Ashish Bajel
Momelotinib is a potent inhibitor of JAK1 and JAK2 that demonstrated efficacy in patients with primary and secondary myelofibrosis. This phase 2, open-label, randomized study evaluated the efficacy and safety of oral once-daily momelotinib (100mg and 200mg) for the treatment of polycythemia vera (PV) and essential thrombocythemia (ET). The primary endpoint for PV was overall response rate (ORR), defined as the proportion of patients with hematocrit <45%, white blood cell count <10×10(9)/L, platelet count ≤400×10(9)/L, and resolution of palpable splenomegaly, each lasting ≥4 weeks...
May 30, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28575698/corrigendum-to-kb004-a-first-in-class-monoclonal-antibody-targeting-the-receptor-tyrosine-kinase-epha3-in-patients-with-advanced-hematologic-malignancies-results-from-a-phase-1-study-leuk-res-50-nov-2016-123-131-pubmed-pmid-27736729
#18
Ronan T Swords, Peter L Greenberg, Andrew H Wei, Simon Durrant, Anjali S Advani, Mark S Hertzberg, Ian D Lewis, Gabriel Rivera, Dita Gratzinger, Alice C Fan, Dean W Felsher, Jorge E Cortes, Justin M Watts, Geoff T Yarranton, Jackie M Walling, Jeffrey E Lancet
No abstract text is available yet for this article.
May 30, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28575699/a-novel-spliced-variant-of-the-tin2-shelterin-is-present-in-chronic-lymphocytic-leukemia
#19
Ganchimeg Ishdorj, Sara E F Kost, Sara Beiggi, Yunli Zang, Spencer B Gibson, James B Johnston
The shelterin proteins play important roles in telomere maintenance and genome stability. These proteins have been found to be mutated in many cancers including CLL. Herein, we demonstrate here the presence of a novel spliced isoform of TIN2S in chronic lymphocytic leukemia (CLL), related to deletion of exon 2 in the TIN2 gene. The expressions of spliced TIN2S mRNA varied widely in CLL and there was an inverse relationship between the mRNA levels of full-length TIN2S and the spliced moiety. Small amounts of spliced TIN2S were also observed in normal B cells but not in T cells...
May 29, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28599189/preclinical-activity-of-ff-10501-01-a-novel-inosine-5-monophosphate-dehydrogenase-inhibitor-in-acute-myeloid-leukemia
#20
Hui Yang, Zhihong Fang, Yue Wei, Zachary S Bohannan, Irene Gañán-Gómez, Ana Alfonso Pierola, Linda J Paradiso, Hiroyuki Iwamura, Guillermo Garcia-Manero
BACKGROUND: FF-10501-01 is a selective inosine monophosphate dehydrogenase (IMPDH) inhibitor that has shown activity in cancer cell lines. We studied whether FF-10501-01 is effective in targeting a variety of hypomethylating agent (HMA)-sensitive and -resistant acute myelogenous leukemia (AML) cell lines. METHODS: We treated multiple cell lines (including HMA-resistant cells) with FF-10501-01 and analyzed proliferation, apoptosis, and cell cycle status. We also assessed HMA-FF-10501-01 combinations and the ability of extracellular guanosine to rescue cell proliferation in FF-10501-01-treated cells...
May 26, 2017: Leukemia Research
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