Habib Moshref Razavi

Metabolic stress on the heart can cause dilation of coronary arterioles for blood flow recruitment. Although potassium ions (K⁺) released from the myocardium are a major mediator for this response, the underlying signaling pathways for vasodilation are incompletely understood. Herein, the roles of smooth muscle inward-rectifier K⁺ channel subtype 2.1 (K_ir2.1) and Na⁺/K⁺-ATPase were examined. Porcine coronary arterioles were isolated, cannulated, and pressurized for vasomotor study. Vessels developed basal tone and dilated concentration-dependently to extraluminal K⁺ from 7 to 20 mM. Higher K⁺ concentrations (25–40 mM) caused graded vasoconstriction. Vasodilation to K⁺ (10 mM) was not altered by endothelial removal, and blockade of ATP-sensitive K⁺ channels, voltage-sensitive K⁺ channels, or calcium-activated K⁺ channels did not affect K⁺-induced vasodilation. However, sustained but not abrupt transient vasodilation to K⁺ was reduced by the nonspecific K_ir channel inhibitor Ba²⁺ or K_ir2.1 channel blocker chloroethylclonidine. The Na⁺/K⁺-ATPase inhibitor ouabain attenuated K⁺-elicited vasodilation, and ouabain with Ba²⁺ abolished the response. Transfection of arterioles with K_ir2.1 antisense oligonucleotides abolished sustained but not transient dilation. It is concluded that extraluminal K⁺ elevation within the physiological range induces initial transient dilation of porcine coronary arterioles by activating smooth muscle Na⁺/K⁺-ATPase and sustained dilation via smooth muscle K_ir2.1 channels.

Metabolic stress on the heart can cause dilation of coronary arterioles for blood flow recruitment. Although potassium ions (K+) released from the myocardium are a major mediator for this response, the underlying signaling pathways for vasodilation are incompletely understood. Herein, roles of smooth muscle inward-rectifier K+ channel subtype 2.1 (Kir2.1) and Na+/K+ ATPase were examined. Porcine coronary arterioles were isolated, cannulated, and pressurized for vasomotor study. Vessels developed basal tone and dilated concentration-dependently to extraluminal K+ from 7 to 20 mM. Higher K+ concentrations (25-40 mM) caused graded vasoconstriction. Vasodilation to K+ (10 mM) was not altered by endothelial removal, and blockade of ATP-sensitive K+ channels, voltage-sensitive K+ channels, or calcium-activated K+ channels did not affect K+-induced vasodilation. However, sustained but not abrupt transient vasodilation to K+ was reduced by nonspecific Kir channel inhibitor Ba2+ or specific Kir2.1 channel blocker chloroethylclonidine. The Na+/K+ ATPase inhibitor ouabain attenuated K+-elicited vasodilation, and ouabain with Ba2+ abolished the response. Transfection of arterioles with Kir2.1 antisense oligonucleotides abolished sustained but not transient dilation. It is concluded that extraluminal K+ elevation within the physiological range induces initial transient dilation of porcine coronary arterioles by activating Na+/K+ ATPase and sustained dilation via smooth muscle Kir2.1 channels.

Key Clinical Message: This is a case of an elderly patient diagnosed with acute myeloid leukemia (AML). While morphological findings, including numerous long, slender, cigar‐shaped Auer rods, suggested AML with t(8;21), cytogenetic and FISH analysis revealed abnormalities in chromosome 11 and the KMT2A (MLL) gene. The patient also exhibited double minutes, typically seen in AML and linked to a complex karyotype and poor prognosis. Correlating morphological findings with molecular genetics and cytogenetics is crucial for accurate diagnosis and treatment.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy which is associated with a distinctive morphologic appearance. However, the morphology is not specific, and diagnostic characterization requires integration of immunophenotypic and genetic testing. We herein report a case of a 35-year-old female patient who presented with worsening cytopenia. A bone marrow aspirate identified medium-sized blastic cells with perinuclear microvacuoles (pearl neckless). Occasional blasts demonstrated a hand mirror appearance. Tandem flow cytometry showed an atypical population of dim CD45 events with expression of CD4, CD56, CD117, CD123, and monocytic markers such as CD64. Fluorescence in situ hybridization (FISH) showed evidence of a KMT2A rearrangement with an unknown partner on chromosome 19. Expression of MPO and muramidase was present. The final diagnosis was acute monocytic leukemia (AMoL). Due to the overlapping features of acute myeloid leukemia and BPDCN, the 5^th Edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours provides new criteria for the diagnosis of BPDCN. Our case highlights the utility of these criteria.

Key Clinical Message: No formal treatment guidelines for MDS/MPN‐RS‐T exist. With salient features such as anemia and thrombocytosis, management is individualized and aims to address anemia, thrombosis, and in some cases acquired von Willebrand's disease. Myelodysplastic/myeloproliferative overlap syndrome with ring sideroblasts and thrombocytosis (MDS/MPN‐RS‐T) is a rare myeloid neoplasm showing myelodysplastic and myeloproliferative features. With extremely raised platelets, possibility of acquired von Willebrand and risk of hemorrhage is increased. With this quandary in mind, a descriptive case and a brief discussion of available treatments ensues.