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Blood Cancer Journal

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https://www.readbyqxmd.com/read/28304403/high-dose-chemotherapy-followed-by-autologous-transplantation-may-overcome-the-poor-prognosis-of-diffuse-large-b-cell-lymphoma-patients-with-myc-bcl2-co-expression
#1
F Maura, A Guidetti, A Pellegrinelli, A Dodero, M Pennisi, C Caprioli, A Testi, L Farina, N Bolli, L F Devizzi, A Cabras, P Corradini
No abstract text is available yet for this article.
March 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28304402/prospective-longitudinal-study-on-quality-of-life-in-relapsed-refractory-multiple-myeloma-patients-receiving-second-or-third-line-lenalidomide-or-bortezomib-treatment
#2
X Leleu, C Kyriakou, I Vande Broek, P Murphy, P Bacon, P Lewis, H Gilet, B Arnould, M T Petrucci
Treatment advances for multiple myeloma (MM) that have prolonged survival emphasise the importance of measuring patients' health-related quality of life (HRQoL) in clinical studies. HRQoL/functioning and symptoms of patients with relapsed/refractory MM (RRMM) receiving second- or third-line lenalidomide or bortezomib treatment were measured in a prospective European multicentre, observational study at different time points. At baseline, patients in the lenalidomide cohort were frailer than in the bortezomib cohort with more rapid disease progression at study entry (more patients with Eastern Cooperative Oncology Group performance status >2, shorter time from diagnosis, more chronic heart failure, higher serum creatinine levels, more patients with dialysis required)...
March 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28282035/randomized-phase-3-study-of-elotuzumab-for-relapsed-or-refractory-multiple-myeloma-eloquent-2-japanese-patient-subanalysis
#3
K Suzuki, K Sunami, K Ohashi, S Iida, T Mori, H Handa, K Matsue, M Miyoshi, E Bleickardt, M Matsumoto, M Taniwaki
No abstract text is available yet for this article.
March 10, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28282034/prognostic-impact-of-bone-marrow-fibrosis-in-polycythemia-vera-validation-of-the-iwg-mrt-study-and-additional-observations
#4
D Barraco, S Cerquozzi, C A Hanson, R P Ketterling, A Pardanani, N Gangat, A Tefferi
In 2012, the International Working Group for Myeloproliferative Neoplasms (MPN) Research and Treatment (IWG-MRT) reported an associations between mild bone marrow (BM) fibrosis (⩾grade 1) in polycythemia vera (PV) and a lower incidence of thrombosis during the clinical course and a higher risk of fibrotic progression. The objective in the current study of 262 patients with PV was to validate these observations and also identify other risk factors for myelofibrosis-free survival (MFFS). About 127 (48%) patients displayed ⩾grade 1 reticulin fibrosis at the time of diagnosis; presenting clinical and laboratory features were not significantly different between patients with or without BM fibrosis...
March 10, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28282033/pi3k%C3%AE-and-pi3k%C3%AE-isoforms-have-distinct-functions-in-regulating-pro-tumoural-signalling-in-the-multiple-myeloma-microenvironment
#5
R E Piddock, N Loughran, C R Marlein, S D Robinson, D R Edwards, S Yu, G E Pillinger, Z Zhou, L Zaitseva, M J Auger, S A Rushworth, K M Bowles
Phosphoinositide-3-kinase and protein kinase B (PI3K-AKT) is upregulated in multiple myeloma (MM). Using a combination of short hairpin RNA (shRNA) lentivirus-mediated knockdown and pharmacologic isoform-specific inhibition we investigated the role of the PI3K p110γ (PI3Kγ) subunit in regulating MM proliferation and bone marrow microenvironment-induced MM interactions. We compared this with inhibition of the PI3K p110δ (PI3kδ) subunit and with combined PI3kδ/γ dual inhibition. We found that MM cell adhesion and migration were PI3Kγ-specific functions, with PI3kδ inhibition having no effect in MM adhesion or migration assays...
March 10, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28282032/germline-mutations-predisposing-to-diffuse-large-b-cell-lymphoma
#6
O C Leeksma, N F de Miranda, H Veelken
No abstract text is available yet for this article.
March 10, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28282031/a-phase-1-2-study-of-chemosensitization-with-plerixafor-plus-g-csf-in-relapsed-or-refractory-acute-myeloid-leukemia
#7
G L Uy, M P Rettig, R M Stone, M Y Konopleva, M Andreeff, K McFarland, W Shannon, T R Fletcher, T Reineck, W Eades, K Stockerl-Goldstein, C N Abboud, M A Jacoby, P Westervelt, J F DiPersio
No abstract text is available yet for this article.
March 10, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28234347/bi-allelic-inactivation-is-more-prevalent-at-relapse-in-multiple-myeloma-identifying-rb1-as-an-independent-prognostic-marker
#8
S S Chavan, J He, R Tytarenko, S Deshpande, P Patel, M Bailey, C K Stein, O Stephens, N Weinhold, N Petty, D Steward, L Rasche, M Bauer, C Ashby, E Peterson, S Ali, J Ross, V A Miller, P Stephens, S Thanendrarajan, C Schinke, M Zangari, F van Rhee, B Barlogie, T I Mughal, F E Davies, G J Morgan, B A Walker
The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse...
February 24, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28234346/splenectomy-as-a-diagnostic-method-in-lymphoma-associated-hemophagocytic-lymphohistiocytosis-of-unknown-origin
#9
J Ma, Z Jiang, T Ding, H Xu, J Song, J Zhang, Y Xie, W Wang
No abstract text is available yet for this article.
February 24, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28234345/anti-leukemic-activity-and-tolerability-of-anti-human-cd47-monoclonal-antibodies
#10
E C Pietsch, J Dong, R Cardoso, X Zhang, D Chin, R Hawkins, T Dinh, M Zhou, B Strake, P-H Feng, M Rocca, C Dos Santos, X Shan, G Danet-Desnoyers, F Shi, E Kaiser, H J Millar, S Fenton, R Swanson, J A Nemeth, R M Attar
CD47, a broadly expressed cell surface protein, inhibits cell phagocytosis via interaction with phagocyte-expressed SIRPα. A variety of hematological malignancies demonstrate elevated CD47 expression, suggesting that CD47 may mediate immune escape. We discovered three unique CD47-SIRPα blocking anti-CD47 monoclonal antibodies (mAbs) with low nano-molar affinity to human and cynomolgus monkey CD47, and no hemagglutination and platelet aggregation activity. To characterize the anti-cancer activity elicited by blocking CD47, the mAbs were cloned into effector function silent and competent Fc backbones...
February 24, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28234344/mutational-landscape-reflects-the-biological-continuum-of-plasma-cell-dyscrasias
#11
A Rossi, M Voigtlaender, S Janjetovic, B Thiele, M Alawi, M März, A Brandt, T Hansen, J Radloff, G Schön, U Hegenbart, S Schönland, C Langer, C Bokemeyer, M Binder
We subjected 90 patients covering a biological spectrum of plasma cell dyscrasias (monoclonal gammopathy of undetermined significance (MGUS), amyloid light-chain (AL) amyloidosis and multiple myeloma) to next-generation sequencing (NGS) gene panel analysis on unsorted bone marrow. A total of 64 different mutations in 8 genes were identified in this cohort. NRAS (28.1%), KRAS (21.3%), TP53 (19.5%), BRAF (19.1%) and CCND1 (8.9%) were the most commonly mutated genes in all patients. Patients with non-myeloma plasma cell dyscrasias showed a significantly lower mutational load than myeloma patients (0...
February 24, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28212374/the-effect-of-body-mass-index-at-diagnosis-on-clinical-outcome-in-children-with-newly-diagnosed-acute-lymphoblastic-leukemia
#12
H M Eissa, Y Zhou, J C Panetta, E K Browne, S Jeha, C Cheng, M V Relling, D Campana, C-H Pui, H Inaba
The impact of body mass index (BMI) at diagnosis on treatment outcome in children with acute lymphoblastic leukemia (ALL) is controversial. We studied 373 children with ALL enrolled on the Total XV study, which prospectively used minimal residual disease (MRD) for risk assignment. MRD on day 19 and at the end of remission induction (day 46), cumulative incidence of relapse/refractory disease (CIR), event-free survival (EFS) and overall survival (OS) were evaluated using sets of four, three and two subgroups based on BMI at diagnosis, along with BMI percentile change during remission induction...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28212373/poly-adp-ribose-polymerase-1-mrna-levels-strongly-correlate-with-the-prognosis-of-myelodysplastic-syndromes
#13
P Diamantopoulos, K Zervakis, P Zervakis, M Sofotasiou, T Vassilakopoulos, I Kotsianidis, A Symeonidis, V Pappa, A Galanopoulos, E Solomou, E Kodandreopoulou, V Papadopoulou, P Korkolopoulou, M Mantzourani, G Kyriakakis, N-A Viniou
Poly (ADP-ribose) polymerase 1 (PARP-1) has a central role in the repair of DNA breaks and is a promising treatment target in malignancy. We measured PARP1 mRNA levels by a SYBR-green-based PCR in the bone marrow of 74 patients with myelodysplastic syndrome (MDS) and correlated them to their demographic, hematologic and prognostic characteristics. The median PARP1 mRNA levels were correlated to the type of MDS (2008/2016 WHO classification, P=0.005) and to the IPSS score (P=0.002). A correlation was also found with the IPSS-R score (P=0...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28211889/clinical-utility-of-the-revised-international-staging-system-in-unselected-patients-with-newly-diagnosed-and-relapsed-multiple-myeloma
#14
N Tandon, S V Rajkumar, B LaPlant, A Pettinger, M Q Lacy, A Dispenzieri, F K Buadi, M A Gertz, S R Hayman, N Leung, R S Go, D Dingli, P Kapoor, Y Lin, Y L Hwa, A L Fonder, M A Hobbs, S R Zeldenrust, J A Lust, W I Gonsalves, S J Russell, S K Kumar
We analyzed the utility of Revised International staging system (RISS) in an unselected cohort of newly diagnosed multiple myeloma (NDMM; cohort 1), and relapsed/refractory multiple myeloma (RRMM; cohort 2) patients. Cohort 1 included 1900 patients seen within 90 days of diagnosis, from 2005 to 2015, while cohort 2 had 887 patients enrolled in 23 clinical trials at Mayo Clinic. The overall survival (OS) and progression-free survival (PFS) was calculated from the time since diagnosis or trial registration. The median estimated follow up was 5 and 2...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28211888/discrepancies-between-the-percentage-of-plasma-cells-in-bone-marrow-aspiration-and-bm-biopsy-impact-on-the-revised-imwg-diagnostic-criteria-of-multiple-myeloma
#15
N Lee, S Y Moon, J-H Lee, H-K Park, S-Y Kong, S-M Bang, J H Lee, S-S Yoon, D S Lee
No abstract text is available yet for this article.
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28211887/germline-mutations-predisposing-to-diffuse-large-b-cell-lymphoma
#16
REVIEW
O C Leeksma, N F de Miranda, H Veelken
Genetic studies of diffuse large B-cell lymphomas (DLBCLs) in humans have revealed numerous targets of somatic mutations and an increasing number of potentially relevant germline alterations. The latter often affect genes involved in DNA repair and/or immune function. In general, defects in these genes also predispose to other conditions. Knowledge of these mutations can lead to disease-preventing measures in the patient and relatives thereof. Conceivably, these germline mutations will be taken into account in future therapy of the lymphoma...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28211886/a-novel-approach-for-the-identification-of-efficient-combination-therapies-in-primary-human-acute-myeloid-leukemia-specimens
#17
I Baccelli, J Krosl, G Boucher, I Boivin, V-P Lavallée, J Hébert, S Lemieux, A Marinier, G Sauvageau
Appropriate culture methods for the interrogation of primary leukemic samples were hitherto lacking and current assays for compound screening are not adapted for large-scale investigation of synergistic combinations. In this study, we report a novel approach that efficiently distills synthetic lethal interactions between small molecules active on primary human acute myeloid leukemia (AML) specimens. In single-dose experiments and under culture conditions preserving leukemia stem cell activity, our strategy considerably reduces the number of tests needed for the identification of promising compound combinations...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28211885/the-novel-bmi-1-inhibitor-ptc596-downregulates-mcl-1-and-induces-p53-independent-mitochondrial-apoptosis-in-acute-myeloid-leukemia-progenitor-cells
#18
Y Nishida, A Maeda, M J Kim, L Cao, Y Kubota, J Ishizawa, A AlRawi, Y Kato, A Iwama, M Fujisawa, K Matsue, M Weetall, M Dumble, M Andreeff, T W Davis, A Branstrom, S Kimura, K Kojima
Disease recurrence is the major problem in the treatment of acute myeloid leukemia (AML). Relapse is driven by leukemia stem cells, a chemoresistant subpopulation capable of re-establishing disease. Patients with p53 mutant AML are at an extremely high risk of relapse. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is required for the self-renewal and maintenance of AML stem cells. Here we studied the effects of a novel small molecule inhibitor of BMI-1, PTC596, in AML cells. Treatment with PTC596 reduced MCL-1 expression and triggered several molecular events consistent with induction of mitochondrial apoptosis: loss of mitochondrial membrane potential, BAX conformational change, caspase-3 cleavage and phosphatidylserine externalization...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28157219/the-role-of-the-extracellular-matrix-in-primary-myelofibrosis
#19
REVIEW
O Leiva, S K Ng, S Chitalia, A Balduini, S Matsuura, K Ravid
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm that arises from clonal proliferation of hematopoietic stem cells and leads to progressive bone marrow (BM) fibrosis. While cellular mutations involved in the development of PMF have been heavily investigated, noteworthy is the important role the extracellular matrix (ECM) plays in the progression of BM fibrosis. This review surveys ECM proteins contributors of PMF, and highlights how better understanding of the control of the ECM within the BM niche may lead to combined therapeutic options in PMF...
February 3, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28157218/expanded-safety-analysis-of-pevonedistat-a-first-in-class-nedd8-activating-enzyme-inhibitor-in-patients-with-acute-myeloid-leukemia-and-myelodysplastic-syndromes
#20
R T Swords, J Watts, H P Erba, J K Altman, M Maris, F Anwer, Z Hua, H Stein, H Faessel, F Sedarati, B J Dezube, F J Giles, B C Medeiros, D J DeAngelo
No abstract text is available yet for this article.
February 3, 2017: Blood Cancer Journal
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