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Leukemia Research

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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
#1
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
#2
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
#3
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
#4
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/28624713/aneuploidy-identification-in-pre-b-acute-lymphoblastic-leukemia-patients-at-diagnosis-by-multiplex-ligation-dependent-probe-amplification-mlpa
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28544907/micrornas-that-affect-the-fanconi-anemia-brca-pathway-are-downregulated-in-imatinib-resistant-chronic-myeloid-leukemia-patients-without-detectable-bcr-abl-kinase-domain-mutations
#14
E Yap, Z A Norziha, A Simbun, N R Tumian, S K Cheong, C F Leong, C L Wong
Chronic myeloid leukemia (CML) patients who do not achieve landmark responses following treatment with imatinib mesylate (IM) are considered IM-resistant. Although IM-resistance can be due to BCR-ABL kinase domain (KD) mutations, many IM-resistant patients do not have detectable BCR-ABL KD mutations. MicroRNAs (miRNAs) are short non-coding RNAs that control gene expression. To investigate the role of miRNAs in IM-resistance, we recruited 8 chronic phase CML patients with IM-resistance who tested negative for BCR-ABL KD mutations and 2 healthy normal controls...
May 18, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28544905/high-serum-levels-of-soluble-interleukin-2-receptor-sil2-r-interleukin-6-il-6-and-tumor-necrosis-factor-alpha-tnf-are-associated-with-adverse-clinical-features-and-predict-poor-outcome-in-diffuse-large-b-cell-lymphoma
#15
Ivan Dlouhy, Xavier Filella, Jordina Rovira, Laura Magnano, Alfredo Rivas-Delgado, Tycho Baumann, Alejandra Martínez-Trillos, Olga Balagué, Antonio Martínez, Blanca González-Farre, Kennosuke Karube, Eva Gine, Julio Delgado, Elías Campo, Armando López-Guillermo
Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with heterogeneous outcomes. To improve accuracy of the international prognostic index score, new biological variables are being investigated. The aim of this study was to determine the prognostic significance of serum levels of different cytokines, namely soluble interleukin-2 receptor (sIL2-R), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF). We analyzed 197 de novo DLBCL patients (91 M/106 F; median age 66 years) treated with immunochemotherapy in a single institution...
May 17, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28549237/haploidentical-allogeneic-hematopoietic-stem-cell-transplantation-compared-to-matched-unrelated-transplantation-for-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#16
Bin Gu, Xiaojin Wu, Guanghua Chen, Xiao Ma, Zhengming Jin, Xiaowen Tang, Yue Han, Chengcheng Fu, Huiying Qiu, Aining Sun, Depei Wu
To investigate the effect of haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), the outcome of 58 patients with Ph+ ALL who received Haplo-HCT (n=42) or matched unrelated donor transplantation (MUD-HCT) (n=16) during the same period were analyzed retrospectively. All patients received a tyrosine kinase inhibitor (TKI)-based regimen before transplantation, and TKI was resumed primarily after transplantation...
May 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28551161/independent-prognostic-significance-of-monosomy-17-and-impact-of-karyotype-complexity-in-monosomal-karyotype-complex-karyotype-acute-myeloid-leukemia-results-from-four-ecog-acrin-prospective-therapeutic-trials
#17
Stephen A Strickland, Zhuoxin Sun, Rhett P Ketterling, Athena M Cherry, Larry D Cripe, Gordon Dewald, Hugo F Fernandez, Gary A Hicks, Rodney R Higgins, Hillard M Lazarus, Mark R Litzow, Selina M Luger, Elisabeth M Paietta, Jacob M Rowe, Gail H Vance, Peter Wiernik, Anne E Wiktor, Yanming Zhang, Martin S Tallman
The presence of a monosomal karyotype (MK+) and/or a complex karyotype (CK+) identifies subcategories of AML with poor prognosis. The prognostic significance of the most common monosomies (monosomy 5, monosomy 7, and monosomy 17) within MK+/CK+AML is not well defined. We analyzed data from 1,592 AML patients age 17-93 years enrolled on ECOG-ACRIN therapeutic trials. The majority of MK+ patients (182/195; 93%) were MK+/CK+ with 87% (158/182) having ≥5 clonal abnormalities (CK≥5). MK+ patients with karyotype complexity ≤4 had a median overall survival (OS) of 0...
May 12, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28549238/risk-factors-and-mechanisms-contributing-to-tki-induced-vascular-events-in-patients-with-cml
#18
REVIEW
Peter Valent, Emir Hadzijusufovic, Gregor Hoermann, Wolfgang Füreder, Gerit-Holger Schernthaner, Wolfgang R Sperr, Rudolf Kirchmair, Dominik Wolf
Vascular adverse events (VAE) are an emerging problem in patients with chronic myeloid leukemia (CML) receiving second-generation BCR-ABL1 tyrosine kinase inhibitors (TKI). Relevant VAE comprise peripheral, cerebral, and coronary artery changes in patients receiving nilotinib, venous and arterial occlusive events during ponatinib therapy, and pulmonary hypertension in patients receiving dasatinib. Although each TKI binds to a unique profile of molecular targets in leukemic cells and vascular cells, the exact etiology of drug-induced vasculopathies remains uncertain...
May 12, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28544906/development-of-a-harmonized-patient-reported-outcome-questionnaire-to-assess-myelofibrosis-symptoms-in-clinical-trials
#19
Chad Gwaltney, Jean Paty, Virginia E Kwitkowski, Ruben A Mesa, Amylou C Dueck, Elektra J Papadopoulos, Lixia Wang, Joseph Feliciano, Stephen Joel Coons
Along with reducing spleen size, relieving symptom severity is a key objective of the treatment of myelofibrosis (MF). Several questionnaires have been developed for patient self-report of MF symptoms in clinical trials and each includes unique instructions, items, and/or response scales. This variability in questionnaire content increases uncertainty; it is unclear which questionnaire is the most appropriate for assessing MF symptoms and it makes comparisons across trials difficult. The Patient-Reported Outcome (PRO) Consortium's MF Working Group (WG) was established to review existing MF symptom questionnaires and to develop a harmonized, consensus-based PRO questionnaire for use in future MF trials...
May 12, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28527402/a-rare-e13a3-b2a3-bcr-abl1-fusion-transcript-with-normal-karyotype-in-chronic-myeloid-leukemia-the-challenges-in-diagnosis-and-monitoring-minimal-residual-disease-mrd
#20
M-H Duan, H Li, H Cai
Patients with chronic myeloid leukemia (CML) have a t (9;22)(q34;q11.2) or variant translocation that results in a BCR-ABL1 fusion gene. For many years, conventional karyotyping has been used as the standard diagnostic tool for t (9;22) (q34;q11.2). However, it has several limitations that may lead to failure for detecting BCR-ABL1 gene rearrangements in around 5% of all CML patients. Although reverse transcription polymerase chain reaction (RT-PCR) has evolved as a sensitive method for detecting BCR-ABL1 translocation, this method fail to detect certain BCR-ABL1 fusion transcript type, such as e13a3 (also known as b2a3), as a result of many commercially available and laboratory-developed primer sets...
May 12, 2017: Leukemia Research
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