Multiple Genomic Alterations, Including a Novel AFF4::IRF1 Fusion Gene, in a Treatment-Refractory Blastic Plasmacytoid Dendritic-Cell Neoplasm: A Case Report and Literature Review.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with an aggressive clinical course and poor prognosis. The genetic abnormalities in BPDCN are heterogeneous; therefore, its molecular pathogenesis and the prognostic importance of genomic alterations associated with the disease are not well defined. Here we report a case of BPDCN with a novel AFF4::IRF1 fusion predicted to lead to a loss-of-function of the IRF1 tumor suppressor, somatic mutations of ASXL1, TET2, and MYD88, as well as multiple intrachromosomal deletions. The patient showed resistance to Tagraxofusp and Venetoclax, and he died about 16 months after diagnosis. Considering the predicted effect of the AFF4::IRF1 fusion on IRF1's antitumor effects and immune regulation, and the possibility of its relevance to the aggressive course observed in this case, we propose further evaluation of the clinical significance of this fusion in BPDCN in future cooperative group studies and the consideration of therapeutic strategies aimed at restoring IRF1-dependent antineoplastic effects in such cases.

Association of Posttraumatic Stress Symptom Severity With Health-Related Quality of Life and Self-Reported Functioning Across 12 Months After Severe Traumatic Brain Injury.

OBJECTIVE: To investigate the relation between posttraumatic stress (PTS) symptom severity and health-related quality of life (HRQoL) after severe traumatic brain injury (TBI). DESIGN: Longitudinal prospective multicenter, cohort study on severe TBI in Switzerland (2007-2011). SETTING: Hospital, rehabilitation unit, and/or patient's living facility. PARTICIPANTS: Patients with severe TBI (N=109) were included in the analyses. Injury severity was determined using the Abbreviated Injury Score of the head region after clinical assessment and initial computed tomography scan. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: HRQoL (Medical Outcomes Study 12-Item Short-Form Health Survey Physical and Mental Component Summaries) and self-reported emotional, cognitive, and interpersonal functioning (Patient Competency Rating Scale for Neurorehabilitation). RESULTS: Multilevel models for patients >50 and ≤50 years of age revealed significant negative associations between PTS symptom severity and interpersonal functioning (P<.001 and P=.002), respectively. Among patients ≤50 years of age, PTS symptom severity was significantly associated with total functioning (P=.001) and emotional functioning (P<.001). Among all patients, PTS symptom severity was significantly associated with cognitive functioning (P<.001) and mental HRQoL (P=.01). CONCLUSIONS: Findings indicate that PTS symptoms after severe TBI are negatively associated with HRQoL and emotional, cognitive, and interpersonal functioning.

Acute myeloid leukemia with a novel AKAP9::PDGFRA fusion transformed from essential thrombocythemia: A case report and mini review.

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy associated with various combinations of gene mutations, epigenetic abnormalities, and chromosome rearrangement-related gene fusions. Despite the significant degree of heterogeneity in its pathogenesis, many gene fusions and point mutations are recurrent in AML and have been employed in risk stratification over the last several decades. Gene fusions have long been recognized for understanding tumorigenesis and their proven roles in clinical diagnosis and targeted therapies. Advances in DNA sequencing technologies and computational biology have contributed significantly to the detection of known fusion genes as well as for the discovery of novel ones. Several recurring gene fusions in AML have been linked to prognosis, treatment response, and disease progression. In this report, we present a case with a long history of essential thrombocythemia and hallmark CALR mutation transforming to AML characterized by a previously unreported AKAP9::PDGFRA fusion gene. We propose mechanisms by which this fusion may contribute to the pathogenesis of AML and its potential as a molecular target for tyrosine kinase inhibitors.