Core Binding Factor Leukemia : Chromatin Remodeling Moves Towards Oncogenic Transcription

Acute myeloid leukemia (AML), the most common acute leukemia in adults, is a heterogeneous malignant clonal disorder arising from multipotent hematopoietic progenitor cells characterized by genetic and concerted epigenetic aberrations. Core binding factor-Leukemia (CBFL) is characterized by the recurrent reciprocal translocations t(8;21)(q22;q22) or inv(16)(p13;q22) that, expressing the distinctive RUNX1-RUNX1T1 (also known as Acute myeloid leukemia1-eight twenty-one, AML1-ETO or RUNX1/ETO) or CBFB-MYH11 (also known as CBF\u3b2-SMMHC) translocation product respectively, disrupt the essential hematopoietic function of the CBF. In the past decade, remarkable progress has been achieved in understanding the structure, three-dimensional (3D) chromosomal topology, and disease-inducing genetic and epigenetic abnormalities of the fusion proteins that arise from disruption of the CBF subunit alpha and beta genes. Although CBFLs have a relatively good prognosis compared to other leukemia subtypes, 40-50% of patients still relapse, requiring intensive chemotherapy and allogenic hematopoietic cell transplantation (alloHCT). To provide a rationale for the CBFL-associated altered hematopoietic development, in this review, we summarize the current understanding on the various molecular mechanisms, including dysregulation of Wnt/\u3b2-catenin signaling as an early event that triggers the translocations, playing a pivotal role in the pathophysiology of CBFL. Translation of these findings into the clinical setting is just beginning by improvement in risk stratification, MRD assessment, and development of targeted therapies

KITLG (KIT ligand)

Review on KITLG (KIT ligand), with data on DNA, on the protein encoded, and where the gene is implicated

PTPN13 (Protein tyrosine phosphatase, non-receptor type 13)

Review on PTPN13 (Protein tyrosine phosphatase, non-receptor type 13), with data on DNA, on the protein encoded, and where the gene is implicated

Integral method coefficients for the ring-core technique to evaluate non-uniform residual stresses

The ring-core technique allows for the determination of non-uniform residual stresses from the surface up to relatively higher depths as compared to the hole-drilling technique. The integral method, which is usually applied to hole-drilling, can also be used for elaborating the results of the ring-core test since these two experimental techniques share the axisymmetric geometry and the 0°–45°–90° layout of the strain gage rosette. The aim of this article is to provide accurate coefficients which can be used for evaluating the residual stress distribution by the ring-core integral method. The coefficients have been obtained by elaborating the results of a very refined plane harmonic axisymmetric finite element model and verified with an independent three-dimensional model. The coefficients for small depth steps were initially provided, and then the values for multiple integer step depths were also derived by manipulating the high-resolution coefficient matrices, thus showing how the present results can be practically used for obtaining the residual stresses according to different depth sequences, even non-uniform. This analysis also allowed the evaluation of the eccentricity effect which turned out to be negligible due to the symmetry of the problem. An applicative example was reported in which the input of the experimentally measured relaxed strains was elaborated with different depth resolutions, and the obtained residual stress distributions were compared

X-Ray Diffraction and Hole-Drilling residual stress measurements of shot peening treatments validated on a calibration bench

The inverse problem of determining residual stresses from diffraction or relaxation methods is notoriously affected by a high sensitivity to errors in input data. A particular care must be devoted to ensuring that their input errors are minimized, and results shall come with a quantification of the corresponding uncertainties. Residual stress measurements are often validated by comparing the results of different techniques. Although this approach can strengthen the measurement confidence, it does not highlight potential biases of the methods. The authors presented a calibration bench [1, 2] which can impose a known bending distribution on a specimen while simultaneously performing an X-Ray Diffraction (XRD) or Hole-Drilling Method (HDM) residual stress measurement. Since the external load can freely be applied and removed, Bueckner’s superposition principle [3] can be exploited to simultaneously identify both the reference bending distribution and the actual residual stress distribution with the same experimental setup. As the first is accurately known, the bench provides a direct estimation of the achieved accuracy. Moreover, it can reveal systematic errors in the chosen procedures. Two shot peening treatments were analyzed on the calibration bench with both XRD and HDM. First, residual stresses on the surface were evaluated with XRD measurements, then electrochemical material removal was performed to investigate stresses at higher depths. After that, HDM measurements were carried out and compared with the results of XRD. Both methods were also used to identify the known bending stresses: that provided an additional validation of the residual stress results

Familial gastrointestinal stromal tumors (GISTs)

Review on Familial gastrointestinal stromal tumors (GISTs), with data on clinics, and the genes involved

KITLG (KIT ligand)

Review on KITLG (KIT ligand), with data on DNA, on the protein encoded, and where the gene is implicated

KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog)

Review on KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog), with data on DNA, on the protein encoded, and where the gene is implicated

Piebaldism

Review on Piebaldism, with data on clinics, and the genes involved