Effect of tyrosine kinase inhibitors on stemness in normal and chronic myeloid leukemia cells.

Although tyrosine kinase inhibitors (TKIs) efficiently cure chronic myeloid leukemia (CML), they can fail to eradicate CML stem cells (CML-SCs). The mechanisms responsible for CML-SC survival need to be understood for designing therapies. Several previous studies suggest that TKIs could modulate CML-SC quiescence. Unfortunately, CML-SCs are insufficiently available. Induced pluripotent stem cells (iPSCs) offer a promising alternative. In this work, we used iPSCs derived from CML patients (Ph+). Ph+ iPSC clones expressed lower levels of stemness markers than normal iPSCs. BCR-ABL1 was found to be involved in stemness regulation and ERK1/2 to have a key role in the signaling pathway. TKIs unexpectedly promoted stemness marker expression in Ph+ iPSC clones. Imatinib also retained quiescence and induced stemness gene expression in CML-SCs. Our results suggest that TKIs might have a role in residual disease and confirm the need for a targeted therapy different from TKIs that could overcome the stemness-promoting effect caused by TKIs. Interestingly, a similar pro-stemness effect was observed in normal iPSCs and hematopoietic SCs. These findings could help to explain CML resistance mechanisms and the teratogenic side-effects of TKIs in embryonic cells.

"Infantile" form of the scimitar syndrome with pulmonary hypertension.

Twenty-five newborns and infants aged < 1 year with the scimitar syndrome and pulmonary hypertension from 12 European pediatric centers were examined. Cardiac failure and severe respiratory insufficiency were always present. In 23 cases, pulmonary hypertension was due to a large shunt between abnormal arteries originating from the abdominal aorta and supplying the lower part of the right lung (vascular sequestration). In the last 2 cases, pulmonary hypertension was secondary to stenosis of the common trunk of the right pulmonary veins. Three of 10 patients who received only medical treatment survived; 2 are doing well, with pulmonary arterial pressures that have returned to normal, and the other had severe residual pulmonary hypertension. Six of 15 patients who underwent surgery survived. There were 5 ligations of a patent ductus arteriosus with 5 deaths, 3 pulmonary resections with 2 deaths, 1 dilation of a tight stenosis of the common trunk of the right pulmonary veins with 1 death, and 6 ligations of the abnormal arterial vessels with 5 surviving patients who are in good condition. Ligation of the abnormal arterial vessels appears to be the best type of treatment.

[Surgical treatment of the scimitar syndrome in children, adolescents and adults. A cooperative study of 37 cases]. / Le traitement chirurgical du syndrome du cimeterre chez l'enfant, l'adolescent et l'adulte. Etude coopérative de 37 cas.

The authors report the results of a cooperative study of 37 operated cases of the scimitar syndrome. The diagnostic procedures, the operative indications, the surgical indications, the postoperative complications and the long-term outcome were reviewed. The results were disappointing irrespective of the surgical technique that was used (reimplantation of the right pulmonary veins in the left atrium, lobectomy, pneumonectomy). Only 12 patients had a satisfactory postoperative outcome and good long-term results; 21 patients had long-term chronic respiratory failure with a reduced exercise capacity and 4 patients died after surgery. Of the 21 patients with long-term sequellae, 17 had a thrombosis of the anastomosis between the right pulmonary veins and the left atrium; this occurred immediately after surgery.

Neonatal endocarditis requiring surgery.

A case of infective endocarditis in a neonate is reported. Echocardiography demonstrated a large (1 X 1.5 cm) vegetation on the anterior mitral leaflet protruding into the ventricle during diastole. The left atrium was enlarged and Doppler showed mitral regurgitation. Excision of the vegetation during effective antibiotic treatment involved no complications. Although histologically the endocarditis was in the early stage of healing, surgical removal of large, floppy vegetations is advocated because of the unpredictable risk of catastrophic embolization.