Phenotypic expression of hypertrophic cardiomyopathy (HCM) and disease course are associated with unfavorable metabolic health. We investigated if Western diet (WD) feeding is sufficient to trigger ca Show more
Phenotypic expression of hypertrophic cardiomyopathy (HCM) and disease course are associated with unfavorable metabolic health. We investigated if Western diet (WD) feeding is sufficient to trigger cardiac hypertrophy and dysfunction in heterozygous (HET) Wild-type (WT) and HET mice (3-months-old) were fed a WD or normal chow (NC) for 8 weeks. Metabolomic analyses on serum revealed systemic metabolic derailment in WD-fed WT and HET mice. Strikingly, only WD-fed HET mice developed cardiac hypertrophy and dysfunction, which was not driven by aggravated cardiac myosin binding protein-C haploinsufficiency. WD reduced oxidative phosphorylation and increased toxic lipids in the heart irrespective of genotype. Cardiac proteomic analyses revealed higher abundance of proteins involved in fatty acid oxidation in WD-fed mice, however this increase was blunted in HET compared to WT mice. Accordingly, cardiac metabolomic and lipidomic analyses showed accumulation of acylcarnitines in WD-fed HET vs WT mice. WD feeding triggered cardiac dysfunction and hypertrophy in otherwise phenotype-negative HET Show less
Myeloid sarcoma (MS), previously known as granulocytic sarcoma or chloroma, is a rare neoplastic condition defined as a tumor mass consisting of myeloblasts or immature myeloid cells occurring at an e Show more
Myeloid sarcoma (MS), previously known as granulocytic sarcoma or chloroma, is a rare neoplastic condition defined as a tumor mass consisting of myeloblasts or immature myeloid cells occurring at an extramedullary site. Clinical presentation is diverse and determined by a tumor mass effect or local organ dysfunction. We report the case of a 25-year-old previously healthy male with rapidly progressive shortness of breath. A chest CT scan demonstrated a heterogenous anterosuperior mediastinal mass with pleural and pericardial invasion. A diagnosis of MS with both myeloid and lymphoid characteristics was made by pathologic, morphologic, and immunophenotypic investigation. Next generation analysis revealed a pathogenic TP53 mutation (c.1035₁₀₃₆insCT, p.Glu346Leufs*25). After 4 cycles of chemotherapy only a partial metabolic response and tumor size reduction was obtained. A pretransplant bone marrow biopsy revealed the progression of disease to acute myeloid leukemia. Cytogenetic analysis demonstrated a t(10; 11)(p12;q21). Fluorescence in situ hybridization confirmed the presence of a PICALM-MLLT10 fusion gene. MS with a mediastinal localization is rare and often misdiagnosed as malignant lymphoma. Acute leukemia harboring a PICALM-MLLT10 fusion gene is characterized by a mixed T cell and myeloid phenotype. The rearrangement is a rare recurrent translocation associated with specific clinical features, as illustrated in this case report. Show less