Treatment-Free Remission in Chronic Myeloid Leukemia Harboring Atypical BCR-ABL1 Transcripts

Discontinuation of tyrosine kinase inhibitors (TKI) is the main goal today in the field of Philadelphia positive chronic myeloid leukemia (Ph + CML) and the criteria to attempt the interruption of therapy are well defined and rely on the possibility to regularly monitor the BCR-ABL1 transcript. Patients harboring atypical transcripts are automatically excluded from protocols due to the absence of a standardized method of quantification of their minimal residual disease (MRD). We report here the outcome of 6 patients with atypical transcripts with a long follow up whose MRD was followed in three cases with digital PCR during their treatment free remission (TFR)

Genetic Screening for Potential New Targets in Chronic Myeloid Leukemia Based on Drosophila Transgenic for Human BCR-ABL1

Chronic myeloid leukemia is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome that originates from the reciprocal translocation t(9;22)(q34;q11.2) and encodes for the constitutively active tyrosine kinase protein BCR-ABL1 from the Breakpoint Cluster Region (BCR) sequence and the Abelson (ABL1) gene. Despite BCR-ABL1 being one of the most studied oncogenic proteins, some molecular mechanisms remain enigmatic, and several of the proteins, acting either as positive or negative BCR-ABL1 regulators, are still unknown. The Drosophila melanogaster represents a powerful tool for genetic investigations and a promising model to study the BCR-ABL1 signaling pathway. To identify new components involved in BCR-ABL1 transforming activity, we conducted an extensive genetic screening using different Drosophila mutant strains carrying specific small deletions within the chromosomes 2 and 3 and the gmrGal4,UAS-BCR-ABL1 4M/TM3 transgenic Drosophila as the background. From the screening, we identified several putative candidate genes that may be involved either in sustaining chronic myeloid leukemia (CML) or in its progression. We also identified, for the first time, a tight connection between the BCR-ABL1 protein and Rab family members, and this correlation was also validated in CML patients. In conclusion, our data identified many genes that, by interacting with BCR-ABL1, regulate several important biological pathways and could promote disease onset and progression

The impact of the revised 17 O(p, \u3b1)14 N reaction rate on 17 O stellar abundances and yields

Context. Material processed by the CNO cycle in stellar interiors is enriched in 17O. When mixing processes from the stellar surface reach these layers, as occurs when stars become red giants and undergo the first dredge up, the abundance of 17O increases. Such an occurrence explains the drop of the 16O/17O observed in RGB stars with mass larger than solar mass 1:5M solar mass. As a consequence, the interstellar medium is continuously polluted by the wind of evolved stars enriched in 17O . Aims. Recently, the Laboratory for Underground Nuclear Astrophysics (LUNA) collaboration released an improved rate of the 17O(p; a)14N reaction. In this paper we discuss the impact that the revised rate has on the 16O/17O ratio at the stellar surface and on 17O stellar yields. Methods.We computed stellar models of initial mass between 1 and 20M solar mass and compared the results obtained by adopting the revised rate of the 17O(p; a)14N to those obtained using previous rates. Results. The post-first dredge up 16O/17O ratios are about 20% larger than previously obtained. Negligible variations are found in the case of the second and the third dredge up. In spite of the larger 17O(p; a)14N rate, we confirm previous claims that an extra-mixing process on the red giant branch, commonly invoked to explain the low carbon isotopic ratio observed in bright low-mass giant stars, marginally affects the 16O/17O ratio. Possible effects on AGB extra-mixing episodes are also discussed. As a whole, a substantial reduction of 17O stellar yields is found. In particular, the net yield of stars with mass ranging between 2 and 20 solar mass is 15 to 40% smaller than previously estimated. Conclusions. The revision of the 17O(p; a)14N rate has a major impact on the interpretation of the 16O/17O observed in evolved giants, in stardust grains and on the 17O stellar yields

Origin of meteoritic stardust unveiled by a revised proton-capture rate of 17O

Stardust grains recovered from meteorites provide highprecision snapshots of the isotopic composition of the stellar environment in which they formed1. Attributing their origin to specific types of stars, however, often proves difficult. Intermediate-mass stars of 4\u20138 solar masses are expected to have contributed a large fraction of meteoritic stardust2,3. Yet, no grains have been found with the characteristic isotopic compositions expected for such stars4,5. This is a long-standing puzzle, which points to serious gaps in our understanding of the lifecycle of stars and dust in our Galaxy. Here we show that the increased proton-capture rate of 17O reported by a recent underground experiment6 leads to 17O/16O isotopic ratios that match those observed in a population of stardust grainsfor proton-burning temperatures of 60\u201380 MK. These temperatures are achieved at the base of the convective envelope during the late evolution of intermediate-mass stars of 4\u20138 solar masses7\u20139, which reveals them as the most likely site of origin of the grains. This result provides direct evidence that these stars contributed to the dust inventory from which the Solar System formed

Advances in radiative capture studies at LUNA with a segmented BGO detector

Studies of charged-particle reactions for low-energy nuclear astrophysics require high sensitivity, which can be achieved by means of detection setups with high efficiency and low backgrounds, to obtain precise measurements in the energy region of interest for stellar scenarios. High-efficiency total absorption spectroscopy is an established and powerful tool for studying radiative capture reactions, particularly if combined with the cosmic background reduction by several orders of magnitude obtained at the Laboratory for Underground Nuclear Astrophysics (LUNA). We present recent improvements in the detection setup with the Bismuth GermaniumOxide (BGO) detector at LUNA, aiming to reduce high-energy backgrounds and to increase the summing detection efficiency. The new design results in enhanced sensitivity of the BGO setup, as we demonstrate and discuss in the context of the first direct measurement of the 65 keV resonance (Ex = 5672 keV) of the 17O(p, γ)18F reaction. Moreover, we show two applications of the BGO detector, which exploit its segmentation. In case of complex γ-ray cascades, e. g. the de-excitation of Ex = 5672 keV in 18F, the BGO segmentation allows to identify and suppress the beam induced background signals that mimic the sum peak of interest. We demonstrate another new application for such a detector in form of in-situ activation measurementsof a reaction with β+ unstable product nuclei, e. g., the 14N(p, γ)15O reactio