RESUMO
A left main coronary artery (LMCA) stenosis without any atherosclerotic changes elsewhere in the coronary artery tree is a rare finding, and some uncommon reasons for luminal narrowing should be considered. An unusual case of non-atherosclerotic LMCA stenosis is reported.A middle-aged patient presented with acute myocardial infarction. An immediate coronary angiography was ordered and revealed a subtotal mid LMCA stenosis. A drug-eluting stent was successfully implanted in the LMCA.Operative revascularisation was recommended. Routine surgery was performed and surprisingly revealed an extended mass of a mediastinal tumour surrounding the aortic root. Histopathological examination of the tumour revealed a poorly differentiated squamous cell carcinoma.Postoperatively, the patient was treated with chemotherapy (carboplatin and docetaxel). Five years after the first admission to our hospital, the patient died as a result of ventricular fibrillation.The differential diagnosis of non-atherosclerotic LMCA stenoses is discussed.
RESUMO
In acute myeloid leukemia (AML), mutational activation of the receptor tyrosine kinase (RTK) Flt3 is frequently involved in leukemic transformation. However, little is known about a possible role of highly expressed wild-type Flt3 in AML. The proto-oncogene c-Cbl is an important regulator of RTK signaling, acting through its ubiquitin ligase activity and as a platform for several signaling adaptor molecules. Here, we analyzed the role of c-Cbl in Flt3 signal transduction and myeloid transformation. C-Cbl physically interacted with Flt3 and was tyrosine phosphorylated in the presence of Flt3-ligand (FL). Overexpression of a dominant-negative form of c-Cbl (Cbl-70Z) inhibited FL-induced Flt3 ubiquitylation and internalization, indicating involvement of c-Cbl in Flt3 signaling. DNA sequencing of AML bone marrow revealed a case with a c-Cbl point mutation (Cbl-R420Q). Cbl-R420Q inhibited Flt3 internalization and ubiquitylation. Coexpression of Cbl-R420Q or Cbl-70Z with Flt3 induced cytokine-independent growth and survival of 32Dcl3 cells in the absence of FL. Also, the mutant Cbl proteins altered the amplitude and duration of Flt3-dependent signaling events. Our results indicate an important role of Cbl proteins in Flt3 signal modulation. Also, the data suggest a novel mechanism of leukemic transformation in AML by mutational inactivation of negative RTK regulators.