How does the NPM1 mutant induce leukemia?

NPM1 is the most frequently mutated gene in AML and the role of the NPM1 mutant in acute myeloid leukemia along with its leukemogenic potential are still under investigation

An Imaging Overview of COVID-19 ARDS in ICU Patients and Its Complications: A Pictorial Review

A significant proportion of patients with COVID-19 pneumonia could develop acute respiratory distress syndrome (ARDS), thus requiring mechanical ventilation, and resulting in a high rate of intensive care unit (ICU) admission. Several complications can arise during an ICU stay, from both COVID-19 infection and the respiratory supporting system, including barotraumas (pneumothorax and pneumomediastinum), superimposed pneumonia, coagulation disorders (pulmonary embolism, venous thromboembolism, hemorrhages and acute ischemic stroke), abdominal involvement (acute mesenteric ischemia, pancreatitis and acute kidney injury) and sarcopenia. Imaging plays a pivotal role in the detection and monitoring of ICU complications and is expanding even to prognosis prediction. The present pictorial review describes the clinicopathological and radiological findings of COVID-19 ARDS in ICU patients and discusses the imaging features of complications related to invasive ventilation support, as well as those of COVID-19 itself in this particularly fragile population. Radiologists need to be familiar with COVID-19's possible extra-pulmonary complications and, through reliable and constant monitoring, guide therapeutic decisions. Moreover, as more research is pursued and the pathophysiology of COVID-19 is increasingly understood, the role of imaging must evolve accordingly, expanding from the diagnosis and subsequent management of patients to prognosis prediction

Mesenchymal cells recruit and regulate T regulatory cells

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Engineering donor mesenchymal cells with IL-7 hastens naive T cell recruitment in vitro and supports immunologic reconstitution after HSCT in NOD/SCID mice

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117: Naive and memory T regulatory cells respond to mesenchymal cells regulation

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A genetic platform to model sarcomagenesis from primary adult mesenchymal stem cells

The regulatory factors governing adult mesenchymal stem cells (MSCs) physiology and their tumorigenic potential are still largely unknown, which substantially delays the identification of effective therapeutic approaches for the treatment of aggressive and lethal form of MSC-derived mesenchymal tumors, such as undifferentiated sarcomas. Here we have developed a novel platform to screen and quickly identify genes and pathways responsible for adult MSCs transformation, modeled undifferentiated sarcoma in vivo, and, ultimately, tested the efficacy of targeting the identified oncopathways. Importantly, by taking advantage of this new platform, we demonstrate the key role of an aberrant LRF-DLK1-SOX9 pathway in the pathogenesis of undifferentiated sarcoma with important therapeutic implications

Patients' preferences for chronic lymphocytic leukemia treatment: The CHOICE study

Chronic lymphocytic leukemia (CLL) therapies differ in efficacy, side effects, route, frequency, and duration of administration. We assessed patient preferences for treatment attributes and evaluated associations with disease stage, treatment line, and socio-demographic characteristics in a cross sectional, observational study conducted at 16 Italian hematology centers. Study visits occurred between February and July 2020; 401 adult patients with CLL (201 Watch and Wait (W & W), 200 treated) participated in a discrete choice experiment (DCE), composed of 8 choices between pairs of treatment profiles with different levels of 5 attributes of currently available CLL treatments (length of response, route and duration of administration, risk of side effects including diarrhea, infections, or organ damage). Health-related quality of life was assessed with the EQ-5D-5L, EORTC QLQ-C30 and QLQ CLL-16. Previously treated patients had longer disease duration (7 vs. 5 years), higher prevalence of serious comorbidities (45.5% vs. 36.2%) and high-risk molecular markers (unmutated IGHV 55.6% vs. 17.1%; TP53 mutation 15.2% vs. 4.0%). Health-related quality of life scores were similar between groups. In the DCE, W & W patients rated "possible occurrence of infections" highest (relative importance [RI] = 36.2%), followed by "treatment and relevant duration" (RI = 28.0%) and "progression-free survival (PFS)" (RI = 16.9%). Previously treated patients rated "treatment and relevant duration" highest (RI = 33.3%), followed by "possible occurrence of infections" (RI = 28.8%), "possible occurrence of organ damage" (RI = 19.4%), and "PFS" (RI = 9.8%). Concern over infection was rated highest overall; unexpectedly PFS was not among the most important criteria in either group, suggesting that the first COVID-19 pandemic wave may have influenced patient preferences and concerns about CLL therapy options

Dactinomycin induces complete remission associated with nucleolar stress response in relapsed/refractory NPM1-mutated AML

Acute myeloid leukemia (AML) with mutated NPM1 accounts for one-third of newly diagnosed AML. Despite recent advances, treatment of relapsed/refractory NPM1-mutated AML remains challenging, with the majority of patients eventually dying due to disease progression. Moreover, the prognosis is particularly poor in elderly and unfit patients, mainly because they cannot receive intensive treatment. Therefore, alternative treatment strategies are needed. Dactinomycin is a low-cost chemotherapeutic agent, which has been anecdotally reported to induce remission in NPM1-mutated patients, although its mechanism of action remains unclear. Here, we describe the results of a single-center phase 2 pilot study investigating the safety and efficacy of single-agent dactinomycin in relapsed/refractory NPM1-mutated adult AML patients, demonstrating that this drug can induce complete responses and is relatively well tolerated. We also provide evidence that the activity of dactinomycin associates with nucleolar stress both in vitro and in vivo in patients. Finally, we show that low-dose dactinomycin generates more efficient stress response in cells expressing NPM1 mutant compared to wild-type cells, suggesting that NPM1-mutated AML may be more sensitive to nucleolar stress. In conclusion, we establish that dactinomycin is a potential therapeutic alternative in relapsed/refractory NPM1-mutated AML that deserves further investigation in larger clinical studies