: A protein-coding circular RNA that regulates DNA damage response in -positive leukemias.

Circular RNAs are a novel class of RNA transcripts, which regulate important cellular functions in health and disease. Herein, we report on the functional relevance of the transcript in acute leukemias. In screening experiments, we found that depletion strongly inhibited the proliferative capacity of leukemic cells with translocations.

Follicular Cholangitis: A Rare Cause of Benign Biliary Stricture.

Introduction: The differential diagnosis of focal biliary strictures comprises both malignant and benign conditions. We report a rare case of follicular cholangitis presenting with segmental stricture of the left hepatic duct.

Case Description: An asymptomatic 59-year-old male with no past medical history presented with dilation of the left intrahepatic bile ducts revealed as an incidental finding on an abdominal ultrasound.

Circular RNAs Could Encode Unique Proteins and Affect Cancer Pathways.

circRNAs constitute a novel class of RNA, generally considered as non-coding RNAs; nonetheless, their coding potential has been under scrutiny. In this work, we systematically explored the predicted proteins of more than 160,000 circRNAs detected by exome capture RNA-sequencing and collected in the MiOncoCirc pan-cancer compendium, including normal and cancer samples from different types of tissues. For the functional evaluation, we compared their primary structure and domain composition with those derived from the same linear mRNAs.

Mitophagy Promotes Resistance to BH3 Mimetics in Acute Myeloid Leukemia.

Unlabelled: BH3 mimetics are used as an efficient strategy to induce cell death in several blood malignancies, including acute myeloid leukemia (AML). Venetoclax, a potent BCL-2 antagonist, is used clinically in combination with hypomethylating agents for the treatment of AML. Moreover, MCL1 or dual BCL-2/BCL-xL antagonists are under investigation.

Delayed Presentation of Non-traumatic Bilateral Leg Pseudoaneurysms Mimicking Soft-Tissue Sarcoma - A Case Report.

Introduction: Non-traumatic pseudoaneurysms are very rare but should be considered as a differential diagnosis on patients presenting with a thigh mass.

Case Report: We present an extremely unusual case of a 70-year-old patient who presented with clinical features of a soft-tissue sarcoma of the thigh that instead was proven to be a non-traumatic pseudoaneurysm. There was also incidental finding of bilateral leg non-traumatic pseudoaneurysms.

Portal-mesenteric vein resection for pancreatic cancer: Results in par with the defined benchmark outcomes.

Background: Patients with pancreatic cancer (PC), which may involve major peripancreatic vessels, have been generally excluded from surgery, as resection was deemed futile. The purpose of this study was to analyze the results of portomesenteric vein resection in borderline resectable or locally advanced PC. This study comprises the largest series of such patients in Greece.

Preoperative Diagnosis of Abdominal Extra-Adrenal Paragangliomas with Fine-Needle Biopsy.

Paragangliomas are rare, non-epithelial neuroendocrine neoplasms originating in paraganglia, for instance the adrenal medulla, or at extra-adrenal locations. The aim of this study was to review the literature regarding abdominal extra-adrenal paragangliomas diagnosed pre-operatively with fine-needle biopsy (FNA and/or FNB). The PubMed database was searched to identify such cases, using a specific algorithm and inclusion/exclusion criteria.

Clinical and molecular relevance of genetic variants in the non-coding transcriptome of patients with cytogenetically normal acute myeloid leukemia.

Expression levels of long non-coding RNA (lncRNA) have been shown to associate with clinical outcome of patients with cytogenetically normal acute myeloid leukemia (CN-AML). However, the frequency and clinical significance of genetic variants in the nucleotide sequences of lncRNA in AML patients is unknown. Herein, we analyzed total RNA sequencing data of 377 younger adults (aged <60 years) with CN-AML, who were comprehensively characterized with regard to clinical outcome.

Precision oncology in AML: validation of the prognostic value of the knowledge bank approach and suggestions for improvement.

Recently, a novel knowledge bank (KB) approach to predict outcomes of individual patients with acute myeloid leukemia (AML) was developed using unbiased machine learning. To validate its prognostic value, we analyzed 1612 adults with de novo AML treated on Cancer and Leukemia Group B front-line trials who had pretreatment clinical, cytogenetics, and mutation data on 81 leukemia/cancer-associated genes available. We used receiver operating characteristic (ROC) curves and the area under the curve (AUC) to evaluate the predictive values of the KB algorithm and other risk classifications.

A precision medicine classification for treatment of acute myeloid leukemia in older patients.

Background: Older patients (≥ 60 years) with acute myeloid leukemia (AML) often have multiple, sequentially acquired, somatic mutations that drive leukemogenesis and are associated with poor outcome. Beat AML is a Leukemia and Lymphoma Society-sponsored, multicenter umbrella study that algorithmically segregates AML patients based upon cytogenetic and dominant molecular abnormalities (variant allele frequencies (VAF) ≥ 0.2) into different cohorts to select for targeted therapies.

Gene expression signature predicts relapse in adult patients with cytogenetically normal acute myeloid leukemia.

Although ∼80% of adult patients with cytogenetically normal acute myeloid leukemia (CN-AML) achieve a complete remission (CR), more than half of them relapse. Better identification of patients who are likely to relapse can help to inform clinical decisions. We performed RNA sequencing on pretreatment samples from 268 adults with de novo CN-AML who were younger than 60 years of age and achieved a CR after induction treatment with standard "7+3" chemotherapy.

Mutational landscape and clinical outcome of patients with de novo acute myeloid leukemia and rearrangements involving 11q23/.

Balanced rearrangements involving the gene, located at 11q23, are among the most frequent chromosome aberrations in acute myeloid leukemia (AML). Because of numerous fusion partners, the mutational landscape and prognostic impact of specific 11q23/ rearrangements are not fully understood. We analyzed clinical features of 172 adults with AML and recurrent 11q23/ rearrangements, 141 of whom had outcome data available.

Author Correction: The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Additional gene mutations may refine the 2017 European LeukemiaNet classification in adult patients with de novo acute myeloid leukemia aged <60 years.

The European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) have become an important tool to assess patients' prognosis and guide treatment. We tested the prognostic impact of the 2017 ELN classification in a large cohort of 863 AML patients aged <60 years similarly treated on Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology studies. Based on multivariable models within each ELN genetic-risk group, we identified additional gene mutations that may refine the 2017 ELN risk classification.

Clinical and functional significance of circular RNAs in cytogenetically normal AML.

Circular RNAs (circRNAs) are noncoding RNA molecules that display a perturbed arrangement of exons, called backsplicing. To examine the prognostic and biologic significance of circRNA expression in cytogenetically normal acute myeloid leukemia (CN-AML), we conducted whole-transcriptome profiling in 365 younger adults (age 18-60 years) with CN-AML. We applied a novel pipeline, called Massive Scan for circRNA, to identify and quantify circRNA expression.

Publisher Correction: The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia.

Long non-coding RNAs (lncRNAs) are important regulatory molecules that are implicated in cellular physiology and pathology. In this work, we dissect the functional role of the HOXB-AS3 lncRNA in patients with NPM1-mutated (NPM1mut) acute myeloid leukemia (AML). We show that HOXB-AS3 regulates the proliferative capacity of NPM1mut AML blasts in vitro and in vivo.

EGFL7 Antagonizes NOTCH Signaling and Represents a Novel Therapeutic Target in Acute Myeloid Leukemia.

Purpose: EGF-like domain 7 (EGFL7) is a secreted protein and recently has been shown to play an important role in acute myeloid leukemia (AML); however, the underlying mechanism by which EGFL7 promotes leukemogenesis is largely unknown.

Experimental Design: Using an antibody interaction array, we measured the ability of EGFL7 to bind directly approximately 400 proteins expressed by primary AML blasts. Primary patient samples were stimulated with recombinant EGFL7 (rEGFL7) or anti-EGFL7 blocking antibody to assess alterations in downstream signaling and the ability to effect blast differentiation and survival.

Portal-Mesenteric Vein Resection in Borderline Pancreatic Cancer; 33 Month-Survival in Patients with Good Performance Status.

Patients with pancreatic cancer (PC), which is not upfront resectable, but borderline, involving major peripancreatic vessels, have not been generally considered for surgery, considering that resection in such a setting may be futile. Retrospective analysis of prospectively collected data on patients with borderline pancreatic adenocarcinoma undergoing pancreatectomy en-block with portal and/or superior mesenteric vein resection in a tertiary referral center in Greece between January 2012 and February 2017. Follow-up was complete up to January 2018.

Clinical and molecular characterization of patients with acute myeloid leukemia and sole trisomies of chromosomes 4, 8, 11, 13 or 21.

Sole trisomies of chromosomes 4, 8, 11, 13 and 21 account for 89-95% of all sole trisomies in adult AML patients. We analyzed clinical and molecular characteristics of 138 de novo AML patients with sole +4, +8, +11, +13 or +21, and compared them with AML patients with those trisomies occurring in addition to other chromosome abnormalities (non-sole trisomy) and with cytogenetically normal AML (CN-AML) patients. Mutations in methylation-related genes were most commonly observed within each sole trisomy group (+4, 55%; +8, 58%; +11, 71%; +13, 71%; +21, 75% of patients).

Mutations associated with a 17-gene leukemia stem cell score and the score's prognostic relevance in the context of the European LeukemiaNet classification of acute myeloid leukemia.

Leukemia stem cells (LSC) are more resistant to standard chemotherapy and their persistence during remission can cause relapse, which is still one of the major clinical challenges in the treatment of acute myeloid leukemia (AML). A better understanding of the mutational patterns and the prognostic impact of molecular markers associated with stemness could lead to better clinical management and improve patients' outcomes. We applied a previously described 17-gene expression score comprising genes differently expressed between LSC and leukemic bulk blasts, for 934 adult patients with AML, and studied associations of the 17-gene LSC score with clinical data and mutation status of 81 genes recurrently mutated in cancer and leukemia.

Genetic Characterization and Prognostic Relevance of Acquired Uniparental Disomies in Cytogenetically Normal Acute Myeloid Leukemia.

Purpose: Uniparental disomy (UPD) is a way cancer cells duplicate a mutated gene, causing loss of heterozygosity (LOH). Patients with cytogenetically normal acute myeloid leukemia (CN-AML) do not have microscopically detectable chromosome abnormalities, but can harbor UPDs. We examined the prognostic significance of UPDs and frequency of LOH in patients with CN-AML.