Zn-Neighbor Cu NQR in Zn-Substituted YBa2Cu3O7-d and YBa2Cu4O8

We studied local electronic states near Zn in optimally doped YBa$_2$(Cu$_{1-x}$Zn_x)$_3$O$_{7-\delta}$ and underdoped YBa$_2$(Cu$_{1-x}$Zn_x)$_4$O$_8$ via satellite signals of plane-site Cu(2) nuclear quadrupole resonance (NQR) spectra. From the relative intensity of Cu NQR spectra, the satellite signals are assigned to Zn-neighbor Cu NQR lines. The Cu nuclear spin-lattice relaxation time of the satellite signal is shorter than that of the main signal, which indicates that the magnetic correlation is locally enhanced near Zn both for the underdoped and the optimally doped systems. The pure YBa$_2$Cu$_4$O$_8$ is a stoichiometric, homogenous, underdoped electronic system; nevertheless, the Zn-induced inhomogeneous magnetic response in the CuO$_2$ plane is more marked than that of the optimally doped YBa$_2$Cu$_3$O$_{7-\delta}$.Comment: 9 pages including 8 figures, to be published in Phys. Rev.

Bcl-2 is a therapeutic target for hypodiploid b-lineage acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. The highest rates of treatment failure occur in specific genetic subsets of ALL, including hypodiploid B-cell ALL (B-ALL), for which effective alternative therapies to current intensive chemotherapy treatments have yet to be developed. Here, we integrated biochemical and genomic profiling with functional drug assays to select effective agents with therapeutic potential against hypodiploid B-ALL. ABT-199, a selective Bcl-2 inhibitor, was effective in reducing leukemic burden in vitro and in vivo in patient-derived xenograft models of hypodiploid B-ALL. Daily oral treatment with ABT-199 significantly increased survival in xenografted mice. The unexpected efficacy of ABT-199 observed in hypodiploid leukemias lacking BIM expression (the major reported mediator of ABT-199-induced apoptosis) led us to investigate the mechanism of action of ABT-199 in the absence of BIM. Treatment with ABT-199 elicited responses in a dose-dependent manner, from cell-cycle arrest at low nanomolar concentrations to cell death at concentrations above 100 nmol/L. Collectively, these results demonstrate the efficacy of Bcl-2 inhibition and potential therapeutic strategy in hypodiploid B-ALL. SIGNIFICANCE: These results demonstrate the efficacy of ABT-199 in vivo and provide encouraging preclinical data of Bcl-2 as a potential target for the treatment of hypodiploid B-ALL.Ernesto Diaz-Flores, Evan Q. Comeaux, Kailyn L. Kim, Ella Melnik, Kyle Beckman, Kara L. Davis, Kevin Wu, Jon Akutagawa, Olga Bridges, Roberta Marino, Margo Wohlfeil, Benjamin S. Braun, Charles G. Mullighan and Mignon L. Lo