Can the Gene Expression Profile of Patients with Acute Myeloid Leukemia Predict Complete Remission Following Induction Therapy?

Recent advances in sequencing technologies and genomics have led to the development of several targeted therapies such as BCL2 and Bromodomain and extra-terminal (BET) protein inhibitors for a more personalized treatment of patients with acute myeloid leukemia (AML), yet the majority of patients still receive standard induction chemotherapy. The molecular profiles of patients who are likely to respond to induction therapy and novel directed therapies remain to be determined. The expression of AML-related genes that are targeted by novel therapies such as BCL2 and BRD4, as well as functionally related genes and associated epigenetic modulators (TET2, EZH2, ASXL1, MYC) were analyzed in a series of 176 consecutive AML patients at multiple points during the disease course - diagnosis (Dx), post-induction (PI), complete remission (CR) and relapse (RL) - and their relationship with clinical variables and outcome investigated. Higher TET2 expression was observed PI and at CR compared to Dx, with significantly superior TET2 expression after induction therapy in the group of patients who reached CR compared to those who did not. Thus, the upregulation of TET2 at PI may be a marker of CR in AML patients. On the other hand, cells with high levels of MYC and BCL2 may be vulnerable to BRD4 inhibition.

Zinc associated nanomaterials and their intervention in emerging respiratory viruses: Journey to the field of biomedicine and biomaterials.

Respiratory viruses represent a severe public health risk worldwide, and the research contribution to tackle the current pandemic caused by the SARS-CoV-2 is one of the main targets among the scientific community. In this regard, experts from different fields have gathered to confront this catastrophic pandemic. This review illustrates how nanotechnology intervention could be valuable in solving this difficult situation, and the state of the art of Zn-based nanostructures are discussed in detail. For virus detection, learning from the experience of other respiratory viruses such as influenza, the potential use of Zn nanomaterials as suitable sensing platforms to recognize the S1 spike protein in SARS-CoV-2 are shown. Furthermore, a discussion about the antiviral mechanisms reported for ZnO nanostructures is included, which can help develop surface disinfectants and protective coatings. At the same time, the properties of Zn-based materials as supplements for reducing viral activity and the recovery of infected patients are illustrated. Within the scope of noble adjuvants to improve the immune response, the ZnO NPs properties as immunomodulators are explained, and potential prototypes of nanoengineered particles with metallic cations (like Zn2+) are suggested. Therefore, using Zn-associated nanomaterials from detection to disinfection, supplementation, and immunomodulation opens a wide area of opportunities to combat these emerging respiratory viruses. Finally, the attractive properties of these nanomaterials can be extrapolated to new clinical challenges.

BCL2 Expression at Post-Induction and Complete Remission Impact Outcome in Acute Myeloid Leukemia.

Advances in acute myeloid leukemia (AML) genomics and targeted therapies include the recently approved BCL2 inhibitor venetoclax. The association between BCL2 expression and patient outcome was analyzed in a series of 176 consecutive AML patients at diagnosis (Dx), post-induction (PI), complete remission (CR) and relapse (RL). Levels increased significantly at relapse (mean 1.07 PI/0.96 CR vs. 2.17 RL, p = 0.05/p = 0.03). In multivariate analysis, high BCL2-Dx were marginally associated with worse progression-free survival, while high PI levels or at CR had an independent negative impact on outcome (PI: HR 1.58, p = 0.014; CR: HR 1.96, p = 0.008). This behavior of high PI or CR BCL2 levels and increased risk was maintained in a homogeneous patient subgroup of age <70 and intermediate cytogenetic risk (PI: HR 2.44, p = 0.037; CR: HR 2.71, p = 0.049). Finally, for this subgroup, high BCL2 at relapse indicated worse overall survival (OS, HR 1.15, p = 0.05). In conclusion, high BCL2 levels PI or at CR had an independent negative impact on patient outcome. Therefore, BCL2 expression is a dynamic marker that may be useful during AML patient follow up, and BCL2 levels at PI and/or CR may influence response to anti-BCL2 therapy.

Photoluminescence of ZnO Nanowires: A Review.

One-dimensional ZnO nanostructures (nanowires/nanorods) are attractive materials for applications such as gas sensors, biosensors, solar cells, and photocatalysts. This is due to the relatively easy production process of these kinds of nanostructures with excellent charge carrier transport properties and high crystalline quality. In this work, we review the photoluminescence (PL) properties of single and collective ZnO nanowires and nanorods. As different growth techniques were obtained for the presented samples, a brief review of two popular growth methods, vapor-liquid-solid (VLS) and hydrothermal, is shown. Then, a discussion of the emission process and characteristics of the near-band edge excitonic emission (NBE) and deep-level emission (DLE) bands is presented. Their respective contribution to the total emission of the nanostructure is discussed using the spatial information distribution obtained by scanning transmission electron microscopy-cathodoluminescence (STEM-CL) measurements. Also, the influence of surface effects on the photoluminescence of ZnO nanowires, as well as the temperature dependence, is briefly discussed for both ultraviolet and visible emissions. Finally, we present a discussion of the size reduction effects of the two main photoluminescent bands of ZnO. For a wide emission (near ultra-violet and visible), which has sometimes been attributed to different origins, we present a summary of the different native point defects or trap centers in ZnO as a cause for the different deep-level emission bands.

ZnO Nanowires/N719 Dye With Different Aspect Ratio as a Possible Photoelectrode for Dye-Sensitized Solar Cells.

The vapor-liquid-solid (VLS) process was applied to fabricate zinc oxide nanowires (ZnO NWs) with a different aspect ratio (AR), morphological, and optical properties. The ZnO NWs were grown on a system that contains a quartz substrate with transparent conductive oxide (TCO) thin film followed by an Al-doped ZnO (AZO) seed layer; both films were grown by magnetron sputtering at room temperature. It was found that the ZnO NWs presented high crystalline quality and vertical orientation from different structural and morphological characterizations. Also, NWs showed a good density distribution of 69 NWs/µm2 with a different AR that offers their capability to be used as possible photoelectrode (anode) in potential future device applications. The samples optical properties were studied using various techniques such as photoluminescence (PL), absorption, and transmittance before and after sensitization with N719 dye. The results demonstrated that NW with 30 nm diameter had the best characteristics as feasible photoelectrode (anode) (high absorption, minimum recombination, high crystallinity). Also, the present samples optical properties were found to be improved due to the existence of N719 dye and Au nanoparticles on the tip of NWs. NWs grown in this work can be used in different photonic and optoelectronic applications.

N719 Derivatives for Application in a Dye-Sensitized Solar Cell (DSSC): A Theoretical Study.

The primary goal of this investigation is to analyze the influence of the chemical modifications on the electronic structures of N719 derivatives for their use in dye-sensitized solar cells (DSSCs), by employing density functional theory. UV-vis spectra indicate that the electronic configurations are essential to study the absorption of solar irradiation and analyze the charge-transport mechanism between the electron-transport layer (ETL), the electrolyte, and the dye. Open- and closed-shell electronic configurations are related to the absorption and the excitation energies of the dye. According to the results reported here, it is possible to say that the best candidates are N719, N719-2, N719-7, and N719-8 (neutral and dianionic). They may be used as useful dye sensitizers due to their band gap and band alignment with the ETL, which contributes to having an effective charge transport during the functioning of the solar device. Another parameter that is reported in this investigation is the light-harvesting efficiency for all studied systems. This could help to improve the performance of the device, since there is an increment in the generation of charge carriers. These results could be useful as a guide for experimental investigations on chemical modifications of these sensitizers.

High resolution melting analysis: a rapid and accurate method to detect CALR mutations.

BACKGROUND: The recent discovery of CALR mutations in essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients without JAK2/MPL mutations has emerged as a relevant finding for the molecular diagnosis of these myeloproliferative neoplasms (MPN). We tested the feasibility of high-resolution melting (HRM) as a screening method for rapid detection of CALR mutations. METHODS: CALR was studied in wild-type JAK2/MPL patients including 34 ET, 21 persistent thrombocytosis suggestive of MPN and 98 suspected secondary thrombocytosis. CALR mutation analysis was performed through HRM and Sanger sequencing. We compared clinical features of CALR-mutated versus 45 JAK2/MPL-mutated subjects in ET. RESULTS: Nineteen samples showed distinct HRM patterns from wild-type. Of them, 18 were mutations and one a polymorphism as confirmed by direct sequencing. CALR mutations were present in 44% of ET (15/34), 14% of persistent thrombocytosis suggestive of MPN (3/21) and none of the secondary thrombocytosis (0/98). Of the 18 mutants, 9 were 52 bp deletions, 8 were 5 bp insertions and other was a complex mutation with insertion/deletion. No mutations were found after sequencing analysis of 45 samples displaying wild-type HRM curves. HRM technique was reproducible, no false positive or negative were detected and the limit of detection was of 3%. CONCLUSIONS: This study establishes a sensitive, reliable and rapid HRM method to screen for the presence of CALR mutations.

Photoluminescence Study of Gallium Nitride Thin Films Obtained by Infrared Close Space Vapor Transport.

Photoluminescence (PL) studies in GaN thin films grown by infrared close space vapor transport (CSVT-IR) in vacuum are presented in this work. The growth of GaN thin films was done on a variety of substrates like silicon, sapphire and fused silica. Room temperature PL spectra of all the GaN films show near band-edge emission (NBE) and a broad blue and green luminescence (BL, GL), which can be seen with the naked eye in a bright room. The sample grown by infrared CSVT on the silicon substrate shows several emission peaks from 2.4 to 3.22 eV with a pronounced red shift with respect to the band gap energy. The sample grown on sapphire shows strong and broad ultraviolet emission peaks (UVL) centered at 3.19 eV and it exhibits a red shift of NBE. The PL spectrum of GaN films deposited on fused silica exhibited a unique and strong blue-green emission peak centered at 2.38 eV. The presence of yellow and green luminescence in all samples is related to native defects in the structure such as dislocations in GaN and/or the presence of amorphous phases. We analyze the material quality that can be obtained by CSVT-IR in vacuum, which is a high yield technique with simple equipment set-up, in terms of the PL results obtained in each case.

TiN nanoparticles: small size-selected fabrication and their quantum size effect.

Size-selected TiN nanoclusters in the range of 4 to 20 nm have been produced by an ionized cluster beam, which combines a glow-discharge sputtering with an inert gas condensation technique. With this method, by controlling the experimental conditions, it was possible to produce nanoparticles with a high control in size. The size distribution of TiN nanoparticles was determined before deposition by mass spectroscopy and confirmed by atomic force microscopy. The size distribution was also analyzed using a high-resolution transmission electron micrograph. The photoluminescence [PL] spectra of TiN nanoparticles at different sizes were also experimentally investigated. We reported, for the first time, the strong visible luminescence of TiN nanoparticles on Si (111) wafer due to the reduced size. We also discussed the PL intensity as a function of the nanoparticle size distribution.

Relevance of renin expression by real-time PCR in acute myeloid leukemia.

The search for useful molecular markers in the diagnosis of AML and in the follow-up of minimal residual disease (MRD) has been the focus of many recent studies. Previous research showed that, while normal bone marrow cells lack expression of renin, myeloid blasts have been reported to do so. The aim was to study the expression of the renin gene by the use of real-time quantitative PCR (RQ-PCR) at diagnosis in acute myeloid leukemia patients (AML) and to assess its possible relevance in the prognosis and outcome of such patients. This study analysed 76 samples from patients with AML, with follow-up of positive patients. Thirty-one patients (41%) were positive for renin gene expression at diagnosis. All renin-positive patients at diagnosis showed no expression during complete remission (CR), but expression recurred in those experiencing relapse and persisted when the disease was refractory to treatment. Although the results suggest that the sub-group of renin-positive AML patients might have a worse outcome and a higher relapse rate (at 5 years, the projected rate of disease-free survival was 18.5 +/- 9.8% for renin-positive and 23.5 +/- 8.8% for renin-negative patients), no significant differences were found. It is believed that further studies should aim to validate whether such a difference exists, using a much larger and homogeneus group of patients.