In vivo analysis of the role of aberrant histone deacetylase recruitment and RARα blockade in the pathogenesis of acute promyelocytic leukemia

The promyelocytic leukemia–retinoic acid receptor α (PML-RARα) protein of acute promyelocytic leukemia (APL) is oncogenic in vivo. It has been hypothesized that the ability of PML-RARα to inhibit RARα function through PML-dependent aberrant recruitment of histone deacetylases (HDACs) and chromatin remodeling is the key initiating event for leukemogenesis. To elucidate the role of HDAC in this process, we have generated HDAC1–RARα fusion proteins and tested their activity and oncogenicity in vitro and in vivo in transgenic mice (TM). In parallel, we studied the in vivo leukemogenic potential of dominant negative (DN) and truncated RARα mutants, as well as that of PML-RARα mutants that are insensitive to retinoic acid. Surprisingly, although HDAC1-RARα did act as a bona fide DN RARα mutant in cellular in vitro and in cell culture, this fusion protein, as well as other DN RARα mutants, did not cause a block in myeloid differentiation in vivo in TM and were not leukemogenic. Comparative analysis of these TM and of TM/PML−/− and p53−/− compound mutants lends support to a model by which the RARα and PML blockade is necessary, but not sufficient, for leukemogenesis and the PML domain of the fusion protein provides unique functions that are required for leukemia initiation

Measurement of inclusive charged current interactions on carbon in a few-GeV neutrino beam

The SciBooNE Collaboration reports a measurement of inclusive charged current interactions of muon neutrinos on carbon with an average energy of 0.8 GeV using the Fermilab Booster Neutrino Beam. We compare our measurement with two neutrino interaction simulations: NEUT and NUANCE. The charged current interaction rates (product of flux and cross section) are extracted by fitting the muon kinematics, with a precision of 6-15% for the energy dependent and 3% for the energy integrated analyses. We also extract CC inclusive interaction cross sections from the observed rates, with a precision of 10-30% for the energy dependent and 8% for the energy integrated analyses. This is the first measurement of the CC inclusive cross section on carbon around 1 GeV. These results can be used to convert previous SciBooNE cross section ratio measurements to absolute cross section values.Comment: 21 pages, 16 figures. Accepted by Phys. Rev. D. Minor revisions to match the accepted versio

Search for Charged Current Coherent Pion Production on Carbon in a Few-GeV Neutrino Beam

The SciBooNE Collaboration has performed a search for charged current coherent pion production from muon neutrinos scattering on carbon, \nu_\mu ^{12}C \to \mu^- ^{12}C \pi^+, with two distinct data samples. No evidence for coherent pion production is observed. We set 90% confidence level upper limits on the cross section ratio of charged current coherent pion production to the total charged current cross section at 0.67\times 10^{-2} at mean neutrino energy 1.1 GeV and 1.36\times 10^{-2} at mean neutrino energy 2.2 GeV.Comment: 18 pages, 16 figures, Minor revisions to match version accepted for publication in Physical Review

Measurement of neutral current coherent neutral pion production on carbon in a few-GeV neutrino beam

The SciBooNE Collaboration reports a measurement of neutral current coherent neutral pion production on carbon by a muon neutrino beam with average energy 0.8 GeV. The separation of coherent from inclusive neutral pion production has been improved by detecting recoil protons from resonant neutral pion production. We measure the ratio of the neutral current coherent neutral pion production to total charged current cross sections to be (1.16 +/- 0.24) x 10-2. The ratio of charged current coherent pion to neutral current coherent pion production is calculated to be 0.14+0.30 -0.28, using our published charged current coherent pion measurement.Comment: seven pages, 6 fiure

Measurement of neutral current coherent neutral pion production on carbon in a few-GeV neutrino beam

The SciBooNE Collaboration reports a measurement of neutral current coherent neutral pion production on carbon by a muon neutrino beam with average energy 0.8 GeV. The separation of coherent from inclusive neutral pion production has been improved by detecting recoil protons from resonant neutral pion production. We measure the ratio of the neutral current coherent neutral pion production to total charged current cross sections to be (1.16 +/- 0.24) x 10-2. The ratio of charged current coherent pion to neutral current coherent pion production is calculated to be 0.14+0.30 -0.28, using our published charged current coherent pion measurement.Comment: seven pages, 6 fiure

Measurement of Inclusive Neutral Current Neutral Pion Production on Carbon in a Few-GeV Neutrino Beam

The SciBooNE Collaboration reports inclusive neutral current neutral pion production by a muon neutrino beam on a polystyrene target (C8H8). We obtain (7.7 \pm 0.5(stat.) \pm 0.5 (sys.)) x 10^(-2) as the ratio of the neutral current neutral pion production to total charged current cross section; the mean energy of neutrinos producing detected neutral pions is 1.1 GeV. The result agrees with the Rein-Sehgal model implemented in our neutrino interaction simulation program with nuclear effects. The spectrum shape of the neutral pion momentum and angle agree with the model. We also measure the ratio of the neutral current coherent pion production to total charged current cross section to be (0.7 \pm 0.4) x 10^(-2).Comment: 17 pages, 23 figures, accepted by Phys. Rev.