Impact of complex NOTCH1 mutations on survival in paediatric T-cell leukaemia

<p>Abstract</p> <p>Background</p> <p>Molecular alterations occur frequently in T-ALL and the potential impact of those abnormalities on outcome is still controversial. The current study aimed to test whether <it>NOTCH1 </it>mutations and additional molecular abnormalities would impact T-ALL outcome in a series of 138 T-ALL paediatric cases.</p> <p>Methods</p> <p>T-ALL subtypes, status of <it>SIL-TAL1 </it>fusion, ectopic expression of <it>TLX3</it>, and mutations in <it>FBXW7</it>, <it>KRAS</it>, <it>PTEN </it>and <it>NOTCH1 </it>were assessed as overall survival (OS) and event-free survival (EFS) prognostic factors. OS and EFS were determined using the Kaplan-Meier method and compared using the log-rank test.</p> <p>Results</p> <p>The frequencies of mutations were 43.5% for <it>NOTCH1</it>, while <it>FBXW7</it>, <it>KRAS </it>and <it>PTEN </it>exhibited frequencies of 19.1%, 9.5% and 9.4%, respectively. In 78.3% of cases, the coexistence of <it>NOTCH1 </it>mutations and other molecular alterations was observed. In multivariate analysis no statistical association was revealed between <it>NOTCH1 </it>mutations and any other variable analyzed. The mean length of the follow-up was 68.4 months and the OS was 50.7%. <it>SIL-TAL1 </it>was identified as an adverse prognostic factor. <it>NOTCH1 </it>mutation status was not associated with outcome, while the presence of <it>NOTCH1 </it>complex mutations (indels) were associated with a longer overall survival (<it>p </it>= 0.031) than point mutations.</p> <p>Conclusion</p> <p><it>NOTCH1 </it>mutations alone or in combination with <it>FBXW7 </it>did not impact T-ALL prognosis. Nevertheless, complex <it>NOTCH1 </it>mutations appear to have a positive impact on OS and the <it>SIL-TAL1 </it>fusion was validated as a negative prognostic marker in our series of T-ALL.</p

An Investigation into the Hydrogen Storage Characteristics of Ca(BH₄)₂/LiNH₂ and Ca(BH₄)₂/NaNH₂: Evidence of Intramolecular Destabilization

We report a study of the hydrogen storage properties of materials that result from ball milling Ca­(BH₄)₂ and MNH₂ (M = Li or Na) in a 1:1 molar ratio. The reaction products were examined experimentally by powder X-ray diffraction, thermogravimetric analysis and differential scanning calorimetry (TGA/DSC), simultaneous thermogravimetric modulated beam mass spectrometry (STMBMS), and temperature-programmed desorption (TPD). The Ca­(BH₄)/LiNH₂ system produces a single crystalline compound assigned to LiCa­(BH₄)₂(NH₂). In contrast, ball milling of the Ca­(BH₄)/NaNH₂ system leads to a mixture of NaBH₄ and Ca­(NH₂)₂ produced by a metathesis reaction and another phase we assign to NaCa­(BH₄)₂(NH₂). Hydrogen desorption from the LiCa­(BH₄)₂(NH₂) compound starts around 150 °C, which is more than 160 °C lower than that from pure Ca­(BH₄)₂. Hydrogen is the major gaseous species released from these materials; however various amounts of ammonia form as well. A comparison of the TGA/DSC, STMBMS, and TPD data suggests that the amount of NH₃ released is lower when the desorption reaction is performed in a closed vessel. There is no evidence for diborane (B₂H₆) release from LiCa­(BH₄)₂(NH₂), but traces of other volatile boron–nitrogen species (B₂N₂H₄ and BN₃H₃) are observed at 0.3 mol % of hydrogen released. Theoretical investigations of the possible crystal structures and detailed phase diagrams of the Li–Ca–B–N–H system were conducted using the prototype electrostatic ground state (PEGS) method and multiple gas canonical linear programming (MGCLP) approaches. The theory is in qualitative agreement with the experiments and explains how ammonia desorption in a closed volume can be suppressed. The reduced hydrogen desorption temperature of LiCa­(BH₄)₂(NH₂) relative to Ca­(BH₄)₂ is believed to originate from intramolecular destabilization

Multilayered gold-nanoparticle/polyimide composite thin film through layer-by-layer assembly

10.1021/la0635045Langmuir232010102-10108LANG