To explore the genetic abnormalities that cooperate with AML1-ETO (AE) fusion gene to cause acute myeloid leukemia (AML) with t(8;21), we screened a number of candidate genes and identified 11 types of mutations in C-KIT gene (mC-KIT), including 6 previously undescribed ones among 26 of 54 (48.1%) cases with t(8;21). To address a possible chronological order between AE and mC-KIT, we showed that, among patients with AE and mC-KIT, most leukemic cells at disease presentation harbored both genetic alteration, whereas in three such cases investigated during complete remission, only AE, but not mC-KIT, could be detected by allele-specific PCR. Therefore, mC-KIT should be a subsequent event on the basis of t(8;21). Furthermore, induced expression of AE in U937-A͞E cells significantly up-regulated mRNA and protein levels of C-KIT. This may lead to an alternative way of C-KIT activation and may explain the significantly higher C-KIT expression in 81.3% of patients with t(8;21) than in patients with other leukemias. These data strongly suggest that t(8;21) AML follows a stepwise model in leukemogenesis, i.e., AE represents the first, fundamental genetic hit to initiate the disease, whereas activation of the C-KIT pathway may be a second but also crucial hit for the development of a full-blown leukemia. Additionally, Gleevec suppressed the C-KIT activity and induced proliferation inhibition and apoptosis in cells bearing C-KIT N822K mutation or overexpression, but not in cells with D816 mC-KIT. Gleevec also exerted a synergic effect in apoptosis induction with cytarabine, thus providing a potential therapeutic for t(8;21) leukemia.A bnormalities in genes that encode transcription factors (TFs) and tyrosine kinases (TKs) represent two classes of the most frequently detected genetic events in human leukemias (1-3). Disruptions of TFs, often as results of recurring chromosomal translocations where fusion genes are generated, may lead to inhibition of hematopoietic differentiation and subsequent apoptosis, whereas mutations or alterations of TKs may confer proliferative and͞or survival advantage to hematopoietic stem͞ progenitor cells. Recent evidence suggests that alterations in TFs and TKs are required to cooperate in causing full-blown leukemia (3, 4). However, whether a causal relationship or a chronological order exists between the two genetic events remains largely unknown in a clinical setting.The t(8;21)(q22;q22), where coding sequences of the AML1 gene on chromosome 21 are juxtaposed to coding sequences of the ETO gene on chromosome 8 generating an AML1-ETO (AE) fusion transcript, represents the most common chromosomal translocation in acute myeloid leukemia (AML) (5). The AE chimeric protein recruits the N-CoR-mSin3-HDAC complex (6) and represses wild-type AML1, which is a crucial TF for hematopoiesis, modifies intranuclear targets of AML1 (5, 7), and even represses genes that normally are not regulated by AML1 (8). At cellular level, the AE fusion protein transforms NIH 3T3 cells and activates TF AP-1 (9), maintai...

Plasmon-polaritons are among the most promising candidates for next generation optical sensors due to their ability to support extremely confined electromagnetic fields and empower strong coupling of light and matter. Here we propose quantum plasmonic arXiv:1908.03543v1 [physics.optics] 9 Aug 2019 an enhanced sensitivity that is no longer dependent on the concentration of antibodyantigen-antibody complexes -down to the single-analyte limit. The quantum plasmonic immunoassay scheme thus not only leads to the development of plasmonic bio-sensing for single molecules but also opens up new pathways towards room-temperature quantum sensing enabled by biomolecular inspired protocols linked with quantum nanoplasmonics.

We extend the recent result of bipartite Bell singlet [Carr and Saffman, Phys. Rev. Lett. 111, (2013)] to a stationary three-dimensional entanglement between two-individual neutral Rydberg atoms. This proposal makes full use of the coherent dynamics provided by Rydberg mediated interaction and the dissipative factor originating from the spontaneous emission of Rydberg state. The numerical simulation of the master equation reveals that both the target state negativity N (ρ∞) and fidelity F(ρ∞) can exceed 99.90%. Furthermore, a steady three-atom singlet state |S3 is also achievable based on the same mechanism.