ETV6::ABL1-Positive Myeloid Neoplasm: A Case of a Durable Response to Imatinib Mesylate without Additional or Previous Treatment

ETV6::ABL1 rearranged neoplasms are rare hematological diseases. To date, about 80 cases have been reported, including myeloid and lymphoid leukemias. The ETV6 gene codes for an ETS family transcription factor and several fusion partners have been described. When translocated, ETV6 causes the constitutive activation of the partner genes. Here, we report the case of a 54-year-old woman with a cryptic insertion of the 3′ region of ABL1 in the ETV6 gene. The patient was first diagnosed with idiopathic hypereosinophilic syndrome, according to the clinical history, conventional cytogenetics, standard molecular analyses and pathologist description. Next generation sequencing of diagnosis samples unexpectedly detected both ETV6::ABL1 type A and B fusion transcripts, which were then confirmed by FISH. The diagnosis was Myeloid/Lymphoid neoplasm with ETV6::ABL1 fusion, and the patient received imatinib mesylate treatment. In a follow-up after more than one year, the patient still maintained the molecular and complete hematological responses. This case highlights the importance of timely and proper diagnostics and prompt tyrosine kinase inhibitor treatment

The NUMEN Project: Toward new experiments with high-intensity beams

The search for neutrinoless double-beta (0νββ) decay is currently a key topic in physics, due to its possible wide implications for nuclear physics, particle physics, and cosmology. The NUMEN project aims to provide experimental information on the nuclear matrix elements (NMEs) that are involved in the expression of 0νββ decay half-life by measuring the cross section of nuclear double-charge exchange (DCE) reactions. NUMEN has already demonstrated the feasibility of measuring these tiny cross sections for some nuclei of interest for the 0νββ using the superconducting cyclotron (CS) and the MAGNEX spectrometer at the Laboratori Nazionali del Sud (LNS.) Catania, Italy. However, since the DCE cross sections are very small and need to be measured with high sensitivity, the systematic exploration of all nuclei of interest requires major upgrade of the facility. R&D for technological tools has been completed. The realization of new radiation-tolerant detectors capable of sustaining high rates while preserving the requested resolution and sensitivity is underway, as well as the upgrade of the CS to deliver beams of higher intensity. Strategies to carry out DCE cross-section measurements with high-intensity beams were developed in order to achieve the challenging sensitivity requested to provide experimental constraints to 0νββ NMEs

Cross-section measurement of two-photon annihilation in-flight of positrons at s=20\sqrt{s}=20 MeV with the PADME detector

The inclusive cross-section of annihilation in flight $e^+e^-\rightarrow\gamma\gamma$ of 430 MeV positrons with atomic electrons of a thin diamond target has been measured with the PADME detector at the Laboratori Nazionali di Frascati. The two photons produced in the process were detected by an electromagnetic calorimeter made of BGO crystals. This measurement is the first one based on the direct detection of the photon pair and one of the most precise for positron energies below 1 GeV. This measurement represents a necessary step to search for dark sector particles and mediators weakly coupled to photons and/or electrons with masses ranging from 1 MeV to 20 MeV with PADME. The measurement agrees with the Next to Leading Order QED prediction within the overall 6% uncertainty.Comment: Submitted to PR

Association of MC1R Variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study

<p><b>Background</b> Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited.</p> <p><b>Methods</b> We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided.</p> <p><b>Results</b> Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10−6 ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; Ptrend = 1.86 × 10−8). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10−6 ≤ P ≤ .02).</p> <p><b>Conclusion</b> Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.</p&gt

One-proton transfer reaction for the O 18 + Ti 48 system at 275 MeV

Single-nucleon transfer reactions are processes that selectively probe single-particle components of the populated many-body nuclear states. In this context, recent efforts have been made to build a unified description of the rich nuclear spectroscopy accessible in heavy-ion collisions. An example of this multichannel approach is the study of the competition between successive nucleon transfer and charge exchange reactions, the latter being of particular interest in the context of single and double beta decay studies. To this extent, the one-proton pickup reaction Ti48(O18,F19)Sc47 at 275 MeV was measured for the first time, under the NUMEN experimental campaign. Differential cross-section angular distribution measurements for the F19 ejectiles were performed at INFN-LNS in Catania by using the MAGNEX large acceptance magnetic spectrometer. The data were analyzed within the distorted-wave and coupled-channels Born approximation frameworks. The initial and final-state interactions were described adopting the São Paulo potential, whereas the spectroscopic amplitudes for the projectile and target overlaps were derived from shell-model calculations. The theoretical cross sections are found to be in very good agreement with the experimental data, suggesting the validity of the optical potentials and the shell-model description of the involved nuclear states within the adopted model space

Commissioning of the PADME experiment with a positron beam

The PADME experiment is designed to search for a hypothetical dark photon A' produced in positron-electron annihilation using a bunched positron beam at the Beam Test Facility of the INFN Laboratori Nazionali di Frascati. The expected sensitivity to the A'-photon mixing parameter ϵ is 10-3, for A' mass ≤ 23.5 MeV/c 2 after collecting ∼1013 positrons-on-target. This paper presents the PADME detector status after commissioning in July 2019. In addition, the software algorithms employed to reconstruct physics objects, such as photons and charged particles, and the calibration procedures adopted are illustrated in detail. The results show that the experimental apparatus reaches the design performance, and is able to identify and measure standard electromagnetic processes, such as positron bremsstrahlung and electron-positron annihilation into two photons

The NUMEN heavy ion multidetector for a complementary approach to the neutrinoless double beta decay

Neutrinos are so far the most elusive known particles, and in the last decades many sophisticated experiments have been set up in order to clarify several questions about their intrinsic nature, in particular their masses, mass hierarchy, intrinsic nature of Majorana or Dirac particles. Evidence of the Neutrinoless Double-Beta Decay (NDBD) would prove that neutrinos are Majorana particles, thus improving the understanding of the universe itself. Besides the search for several large underground experiments for the direct experimental detection of NDBD, the NUMEN experiment proposes the investigation of a nuclear mechanism strongly linked to this decay: the Double Charge Exchange reactions (DCE). As such reactions share with the NDBD the same initial and final nuclear states, they could shed light on the determination of the Nuclear Matrix Elements (NMEs), which play a relevant role in the decay. The physics of DCE is described elsewhere in this issue, while the focus of this paper will be on the challenging experimental apparatus currently under construction in order to fulfil the requirements of the NUMEN experiment. The overall structure of the technological improvement to the cyclotron, along with the newly developed detection systems required for tracking and identifying the reaction products and their final excitation level are described

A constrained analysis of the 40Ca(18O,18F)40K direct charge exchange reaction mechanism at 275 Mev

The40 Ca(18 O,18 F)40 K single charge exchange (SCE) reaction is explored at an incident energy of 275 MeV and analyzed consistently by collecting the elastic scattering and inelastic scattering data under the same experimental conditions. Full quantum-mechanical SCE calculations of the direct mechanism are performed by including microscopic nuclear structure inputs and adopting either a bare optical potential or a coupled channel equivalent polarization potential (CCEP) constrained by the elastic and inelastic data. The direct SCE mechanism describes the magnitude and shape of the angular distributions rather well, thus suggesting the suppression of sequential multi-nucleon transfer processes

The NUMEN heavy ion multidetector for a complementary approach to the neutrinoless double beta decay

Neutrinos are so far the most elusive known particles, and in the last decades many sophisticated experiments have been set up in order to clarify several questions about their intrinsic nature, in particular their masses, mass hierarchy, intrinsic nature of Majorana or Dirac particles. Evidence of the Neutrinoless Double-Beta Decay (NDBD) would prove that neutrinos are Majorana particles, thus improving the understanding of the universe itself. Besides the search for several large underground experiments for the direct experimental detection of NDBD, the NUMEN experiment proposes the investigation of a nuclear mechanism strongly linked to this decay: the Double Charge Exchange reactions (DCE). As such reactions share with the NDBD the same initial and final nuclear states, they could shed light on the determination of the Nuclear Matrix Elements (NMEs), which play a relevant role in the decay. The physics of DCE is described elsewhere in this issue, while the focus of this paper will be on the challenging experimental apparatus currently under construction in order to fulfil the requirements of the NUMEN experiment. The overall structure of the technological improvement to the cyclotron, along with the newly developed detection systems required for tracking and identifying the reaction products and their final excitation level are described

Recent results on Heavy-Ion induced reactions of interest for 0νββ decay

An updated overview of recent results on Heavy-Ion induced reactions of interest for neutrinoless double beta decay is reported in the framework of the NUMEN project. The NUMEN idea is to study heavy-ion induced Double Charge Exchange (DCE) reactions with the aim to get information on the nuclear matrix elements for neutrinoless double beta (0νββ) decay. Moreover, to infer the neutrino average masses from the possible measurement of the half- life of 0νββ decay, the knowledge of the nuclear matrix elements is a crucial aspec