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Recurrent <i>ETNK1</i> mutations in atypical chronic myeloid leukemia
Gambacorti-Passerini, Carlo B.,Donadoni, Carla,Parmiani, Andrea,Pirola, Alessandra,Redaelli, Sara,Signore, Giovanni,Piazza, Vincenzo,Malcovati, Luca,Fontana, Diletta,Spinelli, Roberta,Magistroni, Vera American Society of Hematology 2015 Blood Vol.125 No.3
<P>Despite the recent identification of recurrent <I>SETBP1</I> mutations in atypical chronic myeloid leukemia (aCML), a complete description of the somatic lesions responsible for the onset of this disorder is still lacking. To find additional somatic abnormalities in aCML, we performed whole-exome sequencing on 15 aCML cases. In 2 cases (13.3%), we identified somatic missense mutations in the <I>ETNK1</I> gene. Targeted resequencing on 515 hematological clonal disorders revealed the presence of <I>ETNK1</I> variants in 6 (8.8%) of 68 aCML and 2 (2.6%) of 77 chronic myelomonocytic leukemia samples. These mutations clustered in a small region of the kinase domain, encoding for H243Y and N244S (1/8 H243Y; 7/8 N244S). They were all heterozygous and present in the dominant clone. The intracellular phosphoethanolamine/phosphocholine ratio was, on average, 5.2-fold lower in ETNK1-mutated samples (<I>P</I> < .05). Similar results were obtained using myeloid TF1 cells transduced with ETNK1 wild type, ETNK1-N244S, and ETNK1-H243Y, where the intracellular phosphoethanolamine/phosphocholine ratio was significantly lower in ETNK1-N244S (0.76 ± 0.07) and ETNK1-H243Y (0.37 ± 0.02) than in ETNK1-WT (1.37 ± 0.32; <I>P</I> = .01 and <I>P</I> = .0008, respectively), suggesting that <I>ETNK1</I> mutations may inhibit the catalytic activity of the enzyme. In summary, our study shows for the first time the evidence of recurrent somatic <I>ETNK1</I> mutations in the context of myeloproliferative/myelodysplastic disorders.</P>
Gambacorti‐,Passerini, Carlo,Kantarjian, Hagop M.,Kim, Dong‐,Wook,Khoury, Hanna J.,Turkina, Anna G.,Brü,mmendorf, Tim H.,Matczak, Ewa,Bardy‐,Bouxin, Nathalie,Shapiro, Mark,Turnbu John Wiley and Sons Inc. 2015 American journal of hematology Vol.90 No.9
<P>Long‐term efficacy and safety of bosutinib (≥4 years follow‐up from last enrolled patient) were evaluated in an ongoing phase 1/2 study in the advanced leukemia cohort with prior treatment failure (accelerated‐phase [AP, <I>n =</I> 79] chronic myeloid leukemia [CML], blast‐phase [BP, <I>n =</I> 64] CML, acute lymphoblastic leukemia [ALL, <I>n =</I> 24]). Fourteen AP, 2 BP, and 1 ALL patient remained on bosutinib at 4 years (vs. 38, 8, 1 at 1 year); median (range) treatment durations: 10.2 (0.1–88.6), 2.8 (0.03–55.9), 0.97 (0.3–89.2) months. Among AP and BP patients, 57% and 28% newly attained or maintained baseline overall hematologic response (OHR); 40% and 37% attained/maintained major cytogenetic response (MCyR) by 4 years (most by 12 months). In responders at 1 versus 4 years, Kaplan‐Meier (KM) probabilities of maintaining OHR were 78% versus 49% (AP) and 28% versus 19% (BP); KM probabilities of maintaining MCyR were 65% versus 49% (AP) and 21% versus 21% (BP). Most common AEs (AP, BP) were gastrointestinal (96%; 83%), primarily diarrhea (85%; 64%), which was typically low grade (maximum grade 1/2: 81%; 59%) and transient; no patient discontinued due to diarrhea. Serious AEs occurred in 44 (56%) AP and 37 (58%) BP patients, most commonly pneumonia (<I>n =</I> 9) for AP and pyrexia (<I>n =</I> 6) for BP; 11 and 13 died within 30 days of last dose (2 considered bosutinib‐related [AP] per investigator). Responses were durable in ∼50% AP responders at 4 years (∼25% BP patients responded at year 1, suggesting possible bridge‐to‐transplant role in BP patients); toxicity was manageable.Am. J. Hematol. 90:755–768, 2015. © 2015 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.</P>
Bresser, Dominic,Paillard, Elie,Passerini, Stefano The Korean Electrochemical Society 2014 Journal of electrochemical science and technology Vol.5 No.2
The $Li-O_2$ battery has been attracting much attention recently, due to its very high theoretical capacity compared with Li-ion chemistries. Nevertheless, several studies within the last few years revealed that Li-ion derived electrolytes based on alkyl carbonate solvents, which have been commonly used in the last 27 years, are irreversibly consumed at the $O_2$ electrode. Accordingly, more stable electrolytes are required capable to operate with both the Li metal anode and the $O_2$ cathode. Thus, due to their favorable properties such as non volatility, chemical inertia, and favorable behavior toward the Li metal electrode, ionic liquid-based electrolytes have gathered increasing attention from the scientific community for its application in $Li-O_2$ batteries. However, the scale-up of Li-$O_2$ technology to real application requires solving the mass transport limitation, especially for supplying oxygen to the cathode. Hence, the 'LABOHR' project proposes the introduction of a flooded cathode configuration and the circulation of the electrolyte, which is then used as an oxygen carrier from an external $O_2$ harvesting device to the cathode for freeing the system from diffusion limitation.
Understanding problems of lithiated anodes in lithium oxygen full-cells
Kwak, W. J.,Shin, H. J.,Reiter, J.,Tsiouvaras, N.,Hassoun, J.,Passerini, S.,Scrosati, B.,Sun, Y. K. Royal Society of Chemistry 2016 Journal of Materials Chemistry A Vol.4 No.27
<P>Lithium oxygen batteries are attractive battery systems which can provide high energy density for the next generation. However, even if many research studies have made progress for years, the studies about substitution of Li metal which has inherent limitations in terms of stability and long term cycling properties are terribly deficient. Herein, our group clearly demonstrates the ambiguous unsolved problems of lithium oxygen full-cells using an alternative anode for Li metal by XRD and SEM analysis. The amount of Li source in the alternative anode is limited compared to the quasi-infinite amount of Li source in Li metal. The returning lithium ions during charging form lithium hydroxide which passivates the anode by a side reaction with moisture in the electrolyte and from outside. This report will help to accelerate the development of lithium oxygen full-cells.</P>
Khoury, H. Jean,Cortes, Jorge E.,Kantarjian, Hagop M.,Gambacorti-Passerini, Carlo,Baccarani, Michele,Kim, Dong-Wook,Zaritskey, Andrey,Countouriotis, Athena,Besson, Nadine,Leip, Eric,Kelly, Virginia,Br American Society of Hematology 2012 Blood Vol.119 No.15
<P>Bosutinib, a dual Src/Abl tyrosine kinase inhibitor (TKI), has shown potent activity against chronic myeloid leukemia (CML). This phase 1/2 study evaluated the efficacy and safety of once-daily bosutinib 500 mg in leukemia patients after resistance/intolerance to imatinib. The current analysis included 118 patients with chronic-phase CML who had been pretreated with imatinib followed by dasatinib and/or nilotinib, with a median follow-up of 28.5 months. In this subpopulation, major cytogenetic response was attained by 32% of patients; complete cytogenetic response was attained by 24%, including in one of 3 patients treated with 3 prior TKIs. Complete hematologic response was achieved/maintained in 73% of patients. On-treatment transformation to accelerated/blast phase occurred in 5 patients. At 2 years, Kaplan-Meier-estimated progression-free survival was 73% and estimated overall survival was 83%. Responses were seen across Bcr-Abl mutations, including those associated with dasatinib and nilotinib resistance, except T315I. Bosutinib had an acceptable safety profile; treatment-emergent adverse events were primarily manageable grade 1/2 gastrointestinal events and rash. Grade 3/4 nonhematologic adverse events (> 2% of patients) included diarrhea (8%) and rash (4%). Bosutinib may offer a new treatment option for patients with chronic-phase CML after treatment with multiple TKIs. This trial was registered at www.clinicaltrials.gov as NCT00261846.</P>
Optimized hard carbon derived from starch for rechargeable seawater batteries
Kim, Yongil,Kim, Jae-Kwang,Vaalma, Christoph,Bae, Geun Hyeong,Kim, Guk-Tae,Passerini, Stefano,Kim, Youngsik Elsevier 2018 Carbon Vol.129 No.-
<P><B>Abstract</B></P> <P>The recently introduced seawater battery concept is an eco-friendly energy storage system that offers appealing electrochemical performance. Its radically innovative design, compared to conventional lithium-ion batteries, makes use of seawater as an almost infinite sodium reservoir for the positive electrode and, thereby, avoids the use of expensive, scarce, and toxic elements like nickel and cobalt. So far, the problems identified mostly originate from the available negative electrode active materials. In this study, a starch-derived hard carbon was used to optimize the system. Due to its improved disordered structure compared with commercial hard carbon, the starch hard carbon exhibits an increased reversible capacity, current-rate capability, and cycling ability. The material, in fact, depicts a high maximum power density of 700 W kg<SUP>−1</SUP> (based on hard carbon weight) upon discharge at 900 mA g<SUP>−1</SUP>, while still being active at 2700 mA g<SUP>−1</SUP>. These results represent an important step toward practical application of the sodium-based seawater battery technology.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Oh, Hyo-Jin,Jo, Chang-Heum,Yoon, Chong Seung,Yashiro, Hitoshi,Kim, Sun-Jae,Passerini, Stefano,Sun, Yang-Kook,Myung, Seung-Taek Nature Publishing Group 2016 NPG Asia Materials Vol.8 No.-
<P>In the search for high-capacity anode materials, a facile hydrothermal route has been developed to synthesize phase-pure NiC2O4 center dot 2H(2)O nanorods, which were crystallized into the orthorhombic structure without using templates. To ensure the electrical conductivity of the nanorods, the produced NiC2O4 center dot 2H(2)O nanorods were attached to reduced graphene oxide (rGO) sheets via self-assembly layer-by-layer processes that utilize the electrostatic adsorption that occurs in a poly(diallyldimethylammonium chloride) solution. The high electrical conductivity aided by the presence of rGO significantly improved the electrochemical properties: 933 mAh g(-1) for the charge capacity (oxidation), which showed 87.5% efficiency at the first cycle with a retention of approximately 85% for 100 cycles, and 586 mAh g(-1) at 10 C-rates (10 A g(-1)) for the NiC2O4 center dot 2H(2)O/rGO electrode. The lithium storage processes were involved in the conversion reaction, which were fairly reversible via a transformation to Ni metal accompanied by the formation of a lithium oxalate compound upon discharge (reduction) and restoration to the original NiC2O4 center dot 2H(2)O upon charging (oxidation); this was confirmed via X-ray diffraction, transmission electron microscopy, X-ray photoelectron microscopy and time-of-flight secondary ion mass spectroscopy. We believe that the high rate capacity and rechargeability upon cycling are the result of the unique features of the highly crystalline NiC2O4 center dot 2H(2)O nanorods assisted by conducting rGOs.</P>
Interphase Evolution of a Lithium-Ion/Oxygen Battery
Elia, Giuseppe Antonio,Bresser, Dominic,Reiter, Jakub,Oberhumer, Philipp,Sun, Yang-Kook,Scrosati, Bruno,Passerini, Stefano,Hassoun, Jusef American Chemical Society 2015 ACS APPLIED MATERIALS & INTERFACES Vol.7 No.40
<P>A novel lithium-ion/oxygen battery employing Pyr<SUB>14</SUB>TFSI-LiTFSI as the electrolyte and nanostructured Li<SUB><I>x</I></SUB>Sn–C as the anode is reported. The remarkable energy content of the oxygen cathode, the replacement of the lithium metal anode by a nanostructured stable lithium-alloying composite, and the concomitant use of nonflammable ionic liquid-based electrolyte result in a new and intrinsically safer energy storage system. The lithium-ion/oxygen battery delivers a stable capacity of 500 mAh g<SUP>–1</SUP> at a working voltage of 2.4 V with a low charge–discharge polarization. However, further characterization of this new system by electrochemical impedance spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy reveals the progressive decrease of the battery working voltage, because of the crossover of oxygen through the electrolyte and its direct reaction with the Li<SUB><I>x</I></SUB>Sn–C anode.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/aamick/2015/aamick.2015.7.issue-40/acsami.5b07414/production/images/medium/am-2015-07414p_0008.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/am5b07414'>ACS Electronic Supporting Info</A></P>