The t(6;9)(p22;q34) in myeloid neoplasms: a retrospective study of 16 cases

Among patients with acute myeloid leukemia (AML), the t(6;9) (p22;q34) is a rare but defined subset with a poor prognosis. We report 16 patients with the t(6;9), of whom 13 had AML, 2 had myelodysplastic syndrome (MDS), and 1 had chronic myeloid leukemia in myeloid blast crisis (CML-BC). All except for one were evaluated at diagnosis. The median age was 34.5 (range: 7–62 years), with 12 adults and 12 males. Trilineage dysplasia was present in 13 (81%). Marrow basophilia was seen in only two patients, one of whom had CML-BC. HLA-DR was positive in all 12 patients assessed, CD33 in 11, CD13 in 10, and CD34 in seven. Four patients had one other abnormality apart from the t(6;9). These were the t(9;22) in the patient with CML and deletion 9q, addition 13q, and an isochromosome 8q in the other three patients. There were no complex karyotypes. Fms-related tyrosine kinase 3—internal tandem duplication (FLT3-ITD) mutations were seen in seven of 13 patients. Follow-up details were available for six patients. Three received palliative care, and follow-up details were not available for the other seven. The response to chemotherapy was poor in the remaining patients. The only patients who survived were three out of the four who had allogeneic hematopoietic stem cell transplantation (HSCT).     

Gene regulation of extracellular matrix remodeling in human bone marrow stem cell-seeded tissue-engineered grafts

Tissue-engineered heart valves are prone to early structural deterioration. We hypothesize that cell-scaffold interaction and mechanical deformation results in upregulation of genes related to osteogenic/chondrogenic differentiation and thus changes extracellular matrix (ECM) composition in human bone marrow mesenchymal stem cell (hBMSC)-derived tissue-engineered grafts. hBMSC were expanded and seeded onto poly-glycolic acid/poly-lactic acid scaffold for 14 days. Seeded tissue-engineered constructs (TEC) were subjected to cyclic flexure for 24 h, whereas control TEC was maintained in roller bottles for the same duration. hBMSC, TEC, and mechanically deformed TEC were subjected to gene-array and histological analysis. Expression levels of RNA and/or protein markers related to chondrogenesis (Sox9, MGP, RunX2, Col II, Col X, and Col XI) and osteogenesis (ALPL, BMP2, EDN1, RunX1, and Col I) were increased in TEC compared to unseeded hBMSC. Histological sections of TEC stained positive for Saffranin O, alkaline phosphatase activity, and calcium deposits. The expression levels of the above gene and protein markers further increased in deformed TEC compared to static TEC. Cell-scaffold interactions and mechanical stress results in gene expression suggestive of endochondral-ossification that impact upon ECM composition and may predispose them to eventual calcification.     

Right Ventricle and Tricuspid Valve Function at Midterm After the Fontan Operation for Hypoplastic Left Heart Syndrome: Impact of Shunt Type

This study aimed to evaluate clinical outcomes including hemodynamics, right ventricle (RV) function, and tricuspid valve (TV) function in patients with hypoplastic left heart syndrome (HLHS) at midterm after completion of staged palliation based on the source of pulmonary blood flow provided at stage 1. The records of all patients with HLHS who completed Fontan palliation between 2001 and 2007 were retrospectively reviewed. The outcome variables were RV dysfunction, TV, and neo-atrioventricular (neo-AV) regurgitation (from latest echocardiogram), cardiac index (CI), pulmonary vascular resistance (PVR), pulmonary artery pressure (PAp), and right ventricular end-diastolic pressure (RVEDp) (from latest catheterization). Clinical status was obtained from medical records and by contact with the referring cardiologist if necessary. Of 118 patients undergoing a Fontan for HLHS, 116 had a fenestrated lateral tunnel and 2 had an extracardiac conduit. At the time of stage 1 palliation, 36 patients had a right ventricle-to-pulmonary artery (RV-PA) conduit, and 82 patients had a modified Blalock-Taussig shunt (mBTS). All the patients except one who died of sepsis on extracorporeal membrane oxygenation (ECMO) survived the Fontan operation and were discharged home. At a mean follow-up post-Fontan period of 28.4 months (range, 0.16-95.3 months), three patients had died (2 on the transplantation list and 1 from pulmonary vein stenosis), and one patient had the Fontan circulation taken down. No patient had a heart transplantation. A follow-up echocardiogram was performed for 115 patients (after a mean of 15.6 months for RV-PA and 32.1 months for BTS), and 66 patients underwent a post-Fontan catheterization (after a mean of 15.8 months for RV-PA and 29.3 months for BTS). The hemodynamic results for RV-PA conduit versus BTS were a CI of 3.4 ± 0.8 versus 3.4 ± 1.2, a PVR of 1.8 ± 0.7 versus 1.7 ± 0.8, a PAp of 14.3 ± 3.1 versus 14.2 ± 4.5, and an RVEDp of 7.1 ± 3.3 versus 8.9 ± 5.3. No statistically significant differences were found between shunt types regarding survival or degree of RV dysfunction or in terms of neo-AV regurgitation, CI, PVR, PAp, RVEDp, or rhythm problems. Patients in the BTS group required more tricuspid valvuloplasties and had more tricuspid regurgitation at follow-up evaluation. The patients in the RV-PA group had more PA interventions. In conclusion, the contemporary results after Fontan palliation for HLHS were excellent. At the midterm follow-up evaluation, outcomes and hemodynamic data were similar between shunt types. However, the patients in the BTS group exhibited more tricuspid regurgitation, and the patients in the RV-PA group had increased pulmonary artery interventions.