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Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K

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https://www.readbyqxmd.com/read/28919634/achievement-of-a-negative-minimal-residual-disease-state-after-hypomethylating-agent-therapy-in-older-patients-with-aml-reduces-the-risk-of-relapse
#1
P Boddu, J Jorgensen, H Kantarjian, G Borthakur, T Kadia, N Daver, Y Alvarado, N Pemmaraju, P Bose, K Naqvi, M Yilmaz, S Pierce, M Brandt, C D DiNardo, E J Jabbour, M Konopleva, G Garcia-Manero, J Cortes, F Ravandi
Leukemia accepted article preview online, 18 September 2017. doi:10.1038/leu.2017.285.
September 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28919633/clinical-presentation-and-outcomes-in-light-chain-amyloidosis-patients-with-non-evaluable-serum-free-light-chains
#2
S Sidana, N Tandon, A Dispenzieri, M A Gertz, F K Buadi, M Q Lacy, D Dingli, A L Fonder, S R Hayman, M A Hobbs, W I Gonsalves, Y L Hwa, P Kapoor, R A Kyle, N Leung, R S Go, J A Lust, S J Russell, S R Zeldenrust, V Rajkumar, S K Kumar
Hematologic response criteria in light chain (AL) amyloidosis require the difference in involved and uninvolved free light chains (dFLC) to be at least 5 mg/dl. We describe the clinical presentation and outcomes of newly diagnosed amyloidosis patients with dFLC<5 mg/dl (non-evaluable dFLC; 14%, n=165) compared to patients with dFLC ⩾5 mg/dl (evaluable dFLC; 86%, n=975). Patients with non-evaluable dFLC had less cardiac involvement (40 vs 80%, P<0.001), less liver involvement (11 vs 17%, P=0.04) and a trend towards less gastrointestinal involvement (18 vs 25%, P=0...
September 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28914261/rsk2-is-a-new-pim2-target-with-pro-survival-functions-in-flt3-itd-positive-acute-myeloid-leukemia
#3
M-A Hospital, A Jacquel, F Mazed, E Saland, C Larrue, J Mondesir, R Birsen, A S Green, M Lambert, P Sujobert, E-F Gautier, V Salnot, M Le Gall, J Decroocq, L Poulain, N Jacque, M Fontenay, O Kosmider, C Récher, P Auberger, P Mayeux, D Bouscary, J-E Sarry, J Tamburini
Acute myeloid leukemia (AML) with the FLT3 internal tandem duplication (FLT3-ITD AML) accounts for 20-30% of AML cases. This subtype usually responds poorly to conventional therapies, and might become resistant to FLT3 tyrosine kinase inhibitors (TKIs) due to molecular bypass mechanisms. New therapeutic strategies focusing on resistance mechanisms are therefore urgently needed. Pim kinases are FLT3-ITD oncogenic targets that have been implicated in FLT3 TKI resistance. However, their precise biological function downstream of FLT3-ITD requires further investigation...
September 15, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28914260/high-dose-methotrexate-therapy-significantly-improved-survival-of-adult-acute-lymphoblastic-leukemia-a-phase-iii-study-by-jalsg
#4
T Sakura, F Hayakawa, I Sugiura, T Murayama, K Imai, N Usui, S Fujisawa, T Yamauchi, T Yujiri, K Kakihana, Y Ito, H Kanamori, Y Ueda, Y Miyata, M Kurokawa, N Asou, K Ohnishi, S Ohtake, Y Kobayashi, K Matsuo, H Kiyoi, Y Miyazaki, T Naoe
High-dose methotrexate (Hd-MTX) therapy has recently been applied to the treatment of adult acute lymphoblastic leukemia (ALL) based on pediatric protocols; however, its effectiveness for adult ALL has not yet been confirmed in a rigorous manner. We herein conducted a randomized phase III trial comparing Hd-MTX therapy with intermediate-dose (Id)-MTX therapy. This study was registered at UMIN-CTR (ID: C000000063). Philadelphia chromosome (Ph)-negative ALL patients aged between 25 and 64 years of age were enrolled...
September 15, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28914259/epigenetic-targeting-of-notch1-driven-transcription-using-the-hdaci-panobinostat-is-a-potential-therapy-against-t-cell-acute-lymphoblastic-leukemia
#5
M Waibel, S J Vervoort, I Y Kong, S Heinzel, K M Ramsbottom, B P Martin, E D Hawkins, R W Johnstone
Leukemia accepted article preview online, 15 September 2017. doi:10.1038/leu.2017.282.
September 15, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28904384/targeting-the-vulnerability-to-nad-depletion-in-b-cell-acute-lymphoblastic-leukemia
#6
S Takao, W Chien, V Madan, D-C Lin, L-W Ding, Q-Y Sun, A Mayakonda, M Sudo, L Xu, Y Chen, Y-Y Jiang, S Gery, M Lill, E Park, W Senapedis, E Baloglu, M Müschen, H P Koeffler
Although substantial progress has been made in the treatment of B-cell acute lymphoblastic leukemia (B-ALL), the prognosis of patients with either refractory or relapsed B-ALL remains dismal. Novel therapeutic strategies are needed to improve the outcome of these patients. KPT-9274 is a novel dual inhibitor of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT). PAK4 is a serine/threonine kinase, which regulates a variety of fundamental cellular processes. NAMPT is a rate-limiting enzyme in the salvage biosynthesis pathway of nicotinamide adenine dinucleotide (NAD), which plays a vital role in energy metabolism...
September 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28878352/s1pr1-drives-a-feed-forward-signalling-loop-to-regulate-batf3-and-the-transcriptional-programme-of-hodgkin-lymphoma-cells
#7
K Vrzalikova, M Ibrahim, M Vockerodt, T Perry, S Margielewska, L Lupino, E Nagy, E Soilleux, D Liebelt, R Hollows, A Last, G Reynolds, M Abdullah, H Curley, M Care, D Krappmann, R Tooze, J Allegood, S Spiegel, W Wei, C B J Woodman, P G Murray
The Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (HL) are characterised by the aberrant activation of multiple signalling pathways. Here we show that a subset of HL displays altered expression of sphingosine-1-phosphate (S1P) receptors (S1PR). S1P activates phosphatidylinositide 3-kinase (PI3-K) in these cells that is mediated by the increased expression of S1PR1 and the decreased expression of S1PR2. We also showed that genes regulated by PI3-K signalling pathway in HL cell lines significantly overlap with the transcriptional programme of primary HRS cells...
September 7, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28871137/c-terminal-bre-overexpression-in-11q23-rearranged-and-t-8-16-acute-myeloid-leukemia-is-caused-by-intragenic-transcription-initiation
#8
A E Marneth, K H M Prange, A S A Al Hinai, S M Bergevoet, N Tesi, E Janssen-Megens, B Kim, N Sharifi, M L Yaspo, J Kuster, M A Sanders, E C G Stoetman, J Knijnenburg, T C J M Peters, C M Zwaan, H G Stunnenberg, M M van den Heuvel-Eibrink, T Haferlach, M Fornerod, J H Jansen, P J M Valk, B A van der Reijden, J H A Martens
Overexpression of the BRE (Brain and Reproductive organ-Expressed) gene defines a distinct pediatric and adult acute myeloid leukemia (AML) subgroup. Here we identify a promoter enriched for active chromatin marks in BRE intron 4 causing strong biallelic expression of a previously unknown C-terminal BRE transcript. This transcript starts with BRE intron 4 sequences spliced to exon 5 and downstream sequences, and if translated might code for an N-terminally truncated BRE protein. Remarkably, the new BRE transcript was highly expressed in over 50% of 11q23/KMT2A-rearranged and t(8;16)/KAT6A-CREBBP cases, while it was virtually absent from other AML subsets and normal tissues...
September 5, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28860656/johannes-joseph-van-rood-pioneer-in-immuno-genetics-april-7-1926-july-21-2017
#9
W Fibbe, R P Gale
Leukemia accepted article preview online, 01 September 2017. doi:10.1038/leu.2017.278.
September 1, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28860655/pomalidomide-dexamethasone-in-refractory-multiple-myeloma-long-term-follow-up-of-a-multi-cohort-phase-ii-clinical-trial
#10
S Ailawadhi, J R Mikhael, B R LaPlant, K M Laumann, S Kumar, V Roy, D Dingli, P L Bergsagel, F K Buadi, S V Rajkumar, R Fonseca, M A Gertz, P Kapoor, T Sher, S R Hayman, A K Stewart, A Dispenzieri, R A Kyle, W I Gonsalves, C B Reeder, Y Lin, R S Go, N Leung, T Kourelis, J A Lust, S J Russell, A A Chanan-Khan, M Q Lacy
Despite therapeutic advances, multiple myeloma remains incurable, with limited options for patients with refractory disease. We conducted a large, multi-cohort clinical trial testing various doses and treatment schedules of pomalidomide and dexamethasone (Pom/dex) in patients with refractory multiple myeloma. Overall 345 patients were enrolled to six cohorts based on number and type of prior lines of therapy, pomalidomide dose and schedule. Median prior lines of therapy were 3 with near universal prior exposure to proteasome inhibitors and/or immunomodulatory drugs...
September 1, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28852199/mutant-jak3-phosphoproteomic-profiling-predicts-synergism-between-jak3-inhibitors-and-mek-bcl2-inhibitors-for-the-treatment-of-t-cell-acute-lymphoblastic-leukemia
#11
S Degryse, C E de Bock, S Demeyer, I Govaerts, S Bornschein, D Verbeke, K Jacobs, S Binos, D A Skerrett-Byrne, H C Murray, N M Verrills, P Van Vlierberghe, J Cools, M D Dun
Mutations in the interleukin-7 receptor (IL7R) or the JAK3 kinase occur frequently in T-cell acute lymphoblastic leukemia (T-ALL) and both are able to drive cellular transformation and the development of T-ALL in mouse models. However, the signal transduction pathways downstream of JAK3 mutations remain poorly characterized. Here, we describe the phosphoproteome downstream of the JAK3(L857Q)/(M511I) activating mutations in transformed Ba/F3 lymphocyte cells. Signaling pathways regulated by JAK3 mutants were assessed following acute inhibition of JAK1/JAK3 using the JAK kinase inhibitors ruxolitinib or tofacitinib...
August 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28852198/extracellular-vesicles-as-potential-biomarkers-of-acute-graft-vs-host-disease
#12
G Lia, L Brunello, S Bruno, A Carpanetto, P Omedè, M Festuccia, L Tosti, E Maffini, L Giaccone, M Arpinati, G Ciccone, M Boccadoro, A Evangelista, G Camussi, B Bruno
Acute Graft-vs.-Host Disease (GVHD) is a serious complication after allografting. We carried out an exploratory study to investigate a potential correlation of surface antigens on Extracellular Vesicles (EVs) and acute GVHD. EVs were extracted from serum samples from 41 multiple myeloma patients who underwent allografting. EVs were characterized by flow-cytometry using a panel of 13 antibodies against specific membrane proteins which were reported to be predictive of acute GVHD. We observed a correlation between 3 potential biomarkers expressed on EVs surface and acute GVHD onset by both logistic regression analysis and Cox proportional hazard model...
August 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28832024/activation-of-rhoa-vav1-signaling-in-angioimmunoblastic-t-cell-lymphoma
#13
M Fujisawa, M Sakata-Yanagimoto, S Nishizawa, D Komori, P Gershon, M Kiryu, S Tanzima, K Fukumoto, T Enami, M Muratani, K Yoshida, S Ogawa, K Matsue, N Nakamura, K Takeuchi, K Izutsu, K Fujimoto, T Teshima, H Miyoshi, P Gaulard, K Ohshima, S Chiba
Somatic G17V RHOA mutations were found in 50-70% of angioimmunoblastic T-cell lymphoma (AITL). The mutant RHOA lacks GTP binding capacity, suggesting defects in the classical RHOA signaling. Here, we discovered the novel function of the G17V RHOA: VAV1 was identified as a G17V RHOA-specific binding partner via high throughput screening. We found that binding of G17V RHOA to VAV1 augmented its adaptor function through phosphorylation of 174Tyr, resulting in acceleration of T-cell receptor (TCR) signaling. Enrichment of cytokine and chemokine-related pathways was also evident by the expression of G17V RHOA...
August 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28832023/oncolytic-reovirus-sensitizes-multiple-myeloma-cells-to-anti-pd-l1-therapy
#14
K R Kelly, C M Espitia, W Zhao, K Wu, V Visconte, F Anwer, C M Calton, J S Carew, S T Nawrocki
Leukemia accepted article preview online, 23 August 2017. doi:10.1038/leu.2017.272.
August 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28832022/prevalence-of-somatic-mutations-in-patients-with-aplastic-anemia-using-peripheral-blood-cfdna-as-compared-with-bm
#15
A Albitar, D Townsley, W Ma, I De Dios, V Funari, N S Young, M Albitar
Leukemia accepted article preview online, 23 August 2017. doi:10.1038/leu.2017.271.
August 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28827563/rna-interference-efficiently-targets-human-leukemia-driven-by-a-fusion-oncogene-in-vivo
#16
N Jyotsana, A Sharma, A Chaturvedi, M Scherr, F Kuchenbauer, L Sajti, A Barchanski, R Lindner, F Noyan, K-W Sühs, D Grote-Koska, K Brand, H-P Vornlocher, M Stanulla, B Bornhauser, J-P Bourquin, M Eder, F Thol, A Ganser, R K Humphries, E Ramsay, P Cullis, M Heuser
Leukemia accepted article preview online, 22 August 2017. doi:10.1038/leu.2017.269.
August 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28824170/differences-between-bcl2-break-positive-and-negative-follicular-lymphoma-unraveled-by-whole-exome-sequencing
#17
A Zamo, J Pischimarov, M Schlesner, P Rosenstiel, R Bomben, H Horn, T Grieb, T Nedeva, C López, A Haake, J Richter, L Trümper, C Lawerenz, W Klapper, P Möller, M Hummel, D Lenze, M Szczepanowski, L Flossbach, M Schreder, V Gattei, G Ott, R Siebert, A Rosenwald, E Leich
Depending on disease stage follicular lymphoma (FL) lack the t(14;18) in ~15-~50% of cases. Nevertheless, most of these cases express BCL2.To elucidate mechanisms triggering BCL2-expression and promoting pathogenesis in t(14;18)-negative FL, exonic single nucleotide variant (SNV)-profiles of 28 t(14;18)-positive and 13 t(14;18)-negative FL were analysed, followed by the integration of copy-number changes, copy neutral LOH and published gene-expression data as well as the assessment of immunoglobulin N-glycosylation sites...
August 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28819285/phosphorylation-of-sos1-on-tyrosine-1196-promotes-its-rac-gef-activity-and-contributes-to-bcr-abl-leukemogenesis
#18
S Gerboth, E Frittoli, A Palamidessi, F C Baltanas, S Mogjiborahman, J Rappsilber, C Giuliani, F Troglio, Y Rolland, G Pruneri, S Kreutmair, I Pallavicini, M Zobel, M Cinquanta, S Minucci, C Gomez, E Santos, A L Illert, G Scita
Son of Sevenless 1 (SOS1) is a dual guanine nucleotide exchange factor (GEF) that activates the small GTPases RAC and RAS. While the molecular mechanisms of RAS GEF catalysis have been unveiled, how SOS1 acquires RAC GEF activity and what is the physio-pathological relevance of this activity is much less understood. Here, we show that SOS1 is tyrosine phosphorylated on Y1196 by ABL. Phosphorylation of Y1196 controls SOS1 inter-molecular interaction, is required to promote the exchange of nucleotides on RAC in vitro, and for PDGF activation of RAC and RAC-dependent actin remodeling and cell migration...
August 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28819284/is-there-a-need-for-morphologic-exam-to-detect-relapse-in-aml-if-multi-parameter-flow-cytometry-is-employed
#19
Y Zhou, B L Wood, R B Walter, P S Becker, M-E Percival, M Bar, C Shaw, K Gardner, P Hendrie, J Abkowitz, F R Appelbaum, E Estey
Leukemia accepted article preview online, 18 August 2017. doi:10.1038/leu.2017.263.
August 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28819283/the-c-terminal-multimerization-domain-is-essential-for-leukemia-development-by-cbf%C3%AE-smmhc-in-a-mouse-knockin-model
#20
L Zhao, H Alkadi, E M Kwon, T Zhen, J Lichtenberg, L Alemu, J Cheng, A D Friedman, P P Liu
Leukemia accepted article preview online, 18 August 2017. doi:10.1038/leu.2017.262.
August 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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