TET2 Function in Hematopoietic Malignancies, Immune Regulation, and DNA Repair

Over the last decade, investigation of Ten-Eleven Translocation 2 (TET2) gene function and TET2 mutation have become of increasing interest in the field of hematology. This heightened interest was sparked by the seminal discoveries that (1) TET2 mutation is associated with development of hematological malignancies and that (2) the TET family of proteins is critical in promoting DNA demethylation and immune homeostasis. Since then, additional studies have begun to unravel the question “Does TET2 have additional biological functions in the regulation of hematopoiesis?” Here, we present a mini-review focused on the current understanding of TET2 in hematopoiesis, hematological malignancies, and immune regulation. Importantly, we highlight the critical function that TET2 facilitates in maintaining the stability of the genome. Based on our review of the literature, we provide a new hypothesis that loss of TET2 may lead to dysregulation of the DNA repair response, augment genome instability, and subsequently sensitize myeloid leukemia cells to PARP inhibitor treatment

Electron pairing in the pseudogap state revealed by shot noise in copper oxide junctions

In the quest to understand high-temperature superconductivity in copper oxides, debate has been focused on the pseudogap—a partial energy gap that opens over portions of the Fermi surface in the ‘normal’ state above the bulk critical temperature. The pseudogap has been attributed to precursor superconductivity, to the existence of preformed pairs and to competing orders such as charge-density waves. A direct determination of the charge of carriers as a function of temperature and bias could help resolve among these alternatives. Here we report measurements of the shot noise of tunnelling current in high-quality La_(2−x)Sr)xCuO)4/La)2CuO)4/La_(2−x)Sr)xCuO)4 (LSCO/LCO/LSCO) heterostructures fabricated using atomic layer-by-layer molecular beam epitaxy at several doping levels. The data delineate three distinct regions in the bias voltage–temperature space. Well outside the superconducting gap region, the shot noise agrees quantitatively with independent tunnelling of individual charge carriers. Deep within the superconducting gap, shot noise is greatly enhanced, reminiscent of multiple Andreev reflections. Above the critical temperature and extending to biases much larger than the superconducting gap, there is a broad region in which the noise substantially exceeds theoretical expectations for single-charge tunnelling, indicating pairing of charge carriers. These pairs are detectable deep into the pseudogap region of temperature and bias. The presence of these pairs constrains current models of the pseudogap and broken symmetry states, while phase fluctuations limit the domain of superconductivity

Electron pairing in the pseudogap state revealed by shot noise in copper oxide junctions

In the quest to understand high-temperature superconductivity in copper oxides, debate has been focused on the pseudogap—a partial energy gap that opens over portions of the Fermi surface in the ‘normal’ state above the bulk critical temperature. The pseudogap has been attributed to precursor superconductivity, to the existence of preformed pairs and to competing orders such as charge-density waves. A direct determination of the charge of carriers as a function of temperature and bias could help resolve among these alternatives. Here we report measurements of the shot noise of tunnelling current in high-quality La_(2−x)Sr)xCuO)4/La)2CuO)4/La_(2−x)Sr)xCuO)4 (LSCO/LCO/LSCO) heterostructures fabricated using atomic layer-by-layer molecular beam epitaxy at several doping levels. The data delineate three distinct regions in the bias voltage–temperature space. Well outside the superconducting gap region, the shot noise agrees quantitatively with independent tunnelling of individual charge carriers. Deep within the superconducting gap, shot noise is greatly enhanced, reminiscent of multiple Andreev reflections. Above the critical temperature and extending to biases much larger than the superconducting gap, there is a broad region in which the noise substantially exceeds theoretical expectations for single-charge tunnelling, indicating pairing of charge carriers. These pairs are detectable deep into the pseudogap region of temperature and bias. The presence of these pairs constrains current models of the pseudogap and broken symmetry states, while phase fluctuations limit the domain of superconductivity

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Acute WT1-positive promyelocytic leukemia with hypogranular variant morphology, bcr-3 isoform of PML-RARα and Flt3-ITD mutation: a rare case report

ABSTRACT CONTEXT: Acute promyelocytic leukemia (APL) accounts for 8% to 10% of cases of acute myeloid leukemia (AML). Remission in cases of high-risk APL is still difficult to achieve, and relapses occur readily. CASE REPORT: Here, we describe a case of APL with high white blood cell counts in blood tests and hypogranular variant morphology in bone marrow, together with fms-like tyrosine kinase-3 with internal tandem duplication mutations (FLT3-ITD), and bcr-3 isoform of PML-RARα. Most importantly, we detected high level of Wilms’ tumor gene (WT1) in marrow blasts, through the reverse transcription polymerase chain reaction (RT-PCR). To date, no clear conclusions about an association between WT1 expression levels and APL have been reached. This patient successively received a combined treatment regimen consisting of hydroxycarbamide, arsenic trioxide and idarubicin plus cytarabine, which ultimately enabled complete remission. Unfortunately, he subsequently died of sudden massive hemoptysis because of pulmonary infection. CONCLUSION: Based on our findings and a review of the literature, abnormal functioning of WT1 may be a high-risk factor in cases of APL. Further studies aimed towards evaluating the impact of WT1 expression on the prognosis for APL patients are of interest

Clinical characteristics in immune thrombocytopenia patients after COVID-19 vaccination

It is well documented that COVID-19 vaccines greatly reduce the severity and complications of SARS-CoV-2 infection. However, it has been reported that COVID-19 related vaccines may induce or exacerbate autoimmune hematological disorders, for example, a decrease in platelet numbers characteristic of immune thrombocytopenia (ITP). To investigate this, we retrospectively reported, for the first time, the clinical characteristics of 42 ITP patients after COVID-19 vaccination in southwest China. Of the 42 patients, 28 patients were historically diagnosed ITP, and their platelet counts (PC) decrease mainly occurred after the first-dose vaccinations. The average PC after vaccination was 39.5 × 109/L and recovered to an average of 80.6 × 109/L after treatment. Efficacy of treatment was 90%, and only 10% maintained low PC at the third month of treatment. More interestingly, of the 42 patients, 14 were newly diagnosed ITP following vaccination. Of these 14 patients, 6 patients (43%) were found PC deterioration after the first vaccine dose, and 7 patients (50%) after the second dose. Fortunately, the peripheral PC of all 14 patients recovered significantly after treatment, and the average PC was 139.4 × 109/L, including 8 CRs (complete response) and 6 PRs (partial response). Notably, 9 of the 14 cases were found to have abnormal immune indices when thrombocytopenia diagnosed. No severe organ hemorrhage was found in either subgroup. These results are reassuring the vaccine safety for ITP patients, in that the risks of aggravating thrombocytopenia by COVID-19 vaccination do exist, but it was transient and can be effectively controlled through intensive clinical monitoring and management