Key Points• Germline GATA2 mutations account for 15% of advanced and 7% of all primary pediatric MDS and do not influence overall survival. • The majority (72%) of adolescents with MDS and monosomy 7 carry an underlying GATA2 deficiency.Germline GATA2 mutations cause cellular deficiencies with high propensity for myeloid disease. We investigated 426 children and adolescents with primary myelodysplastic syndrome (MDS) and 82 cases with secondary MDS enrolled in 2 consecutive prospective studies of the European Working Group of MDS in Childhood (EWOG-MDS) conducted in Germany over a period of 15 years. Germline GATA2 mutations accounted for 15% of advanced and 7% of all primary MDS cases, but were absent in children with MDS secondary to therapy or acquired aplastic anemia. Mutation carriers were older at diagnosis and more likely to present with monosomy 7 and advanced disease compared with wild-type cases. For stratified analysis according to karyotype, 108 additional primary MDS patients registered with EWOG-MDS were studied. Overall, we identified 57 MDS patients with germline GATA2 mutations. GATA2 mutations were highly prevalent among patients with monosomy 7 (37%, all ages) reaching its peak in adolescence (72% of adolescents with monosomy 7). Unexpectedly, monocytosis was more frequent in GATA2-mutated patients. However, when adjusted for the selection bias from monosomy 7, mutational status had no effect on the hematologic phenotype. Finally, overall survival and outcome of hematopoietic stem cell transplantation (HSCT) were not influenced by mutational status. This study identifies GATA2 mutations as the most common germline defect predisposing to pediatric MDS with a very high prevalence in adolescents with monosomy 7. GATA2 mutations do not confer poor prognosis in childhood MDS. However, the high risk for progression to advanced disease must guide decision-making toward timely

We describe the introduction of titanium centers to cubic MCM-48 and SBA-15 mesoporous silica by hydrothermal and postsynthetic grafting techniques. MCM-48 was hydrothermally prepared with a gemini surfactant that favors the cubic phase and leads to a high degree of long-range pore ordering. This phase was chosen due to its high surface area (1100-1300 m 2 /g) and its three-dimensional, bicontinuous pore array. SBA-15, synthesized with a block copolymer template under acidic conditions, has a surface area from 600 to 900 m 2 /g and an average pore diameter of 69 Å, compared to 24-27 Å for MCM-48. Alkoxide precursors of titanium were used to prepare samples of Ti-MCM-48 and Ti-SBA-15. We have detailed the bulk and molecular structure of both the silica framework and the local bonding environment of the titanium ions within each matrix. X-ray powder diffraction and nitrogen adsorption shows the pore structure is maintained despite some shrinkage of the pore diameter at high Ti loadings by grafting methods. UV-visible and Raman spectroscopy indicate that grafting produces the least amount of Ti-O-Ti bonds and instead favors isolated tetrahedral and octahedral titanium centers. High-resolution photoacoustic FTIR spectra demonstrated the presence of intermediate range order within the silicate walls of MCM-48, established the consumption of surface silanols to form Si-O-Ti bonds by grafting, and resolved the characteristic IR absorbance at 960 cm -1 , occurring in titanium silicates, into two components. All three spectroscopic techniques, including in situ Raman, reveal the reactive intermediates formed when the materials are contacted with hydrogen peroxide.