MTSS1 is a critical epigenetically regulated tumor suppressor in CML

Chronic myeloid leukemia (CML) is driven by malignant stem cells that can persist despite therapy. We have identified Metastasis suppressor 1 (Mtss1/MIM) to be downregulated in hematopoietic stem and progenitor cells from leukemic transgenic SCLtTA/Bcr-Abl mice and in patients with CML at diagnosis, and Mtss1 was restored when patients achieved complete remission. Forced expression of Mtss1 decreased clonogenic capacity and motility of murine myeloid progenitor cells and reduced tumor growth. Viral transduction of Mtss1 into lineage depleted SCLtTA/Bcr-Abl bone marrow cells decreased leukemic cell burden in recipients, and leukemogenesis was reduced upon injection of Mtss1 overexpressing murine myeloid 32D cells. Tyrosine kinase inhibitor (TKI) therapy and reversion of Bcr-Abl expression increased Mtss1 expression but failed to restore it to control levels. CML patient samples revealed higher DNA methylation of specific Mtss1 promoter CpG sites that contain binding sites for Kaiso and Rest transcription factors. In summary, we identified a novel tumor suppressor in CML stem cells that is downregulated by both Bcr-Abl kinase-dependent and -independent mechanisms. Restored Mtss1 expression markedly inhibits primitive leukemic cell biology in vivo, providing a therapeutic rationale for the Bcr-Abl-Mtss1 axis to target TKI resistant CML stem cells in patients

Off-Forward Parton Distributions

Recently, there have been some interesting developments involving off-forward parton distributions of the nucleon, deeply virtual Compton scattering, and hard diffractive vector-meson production. These developments are triggered by the realization that the off-forward distributions contain information about the internal spin structure of the nucleon and that diffractive electroproduction of vector mesons depends on these unconventional distributions. This paper gives a brief overview of the recent developments

Proof of Factorization for Deeply Virtual Compton Scattering in QCD

We show that factorization holds for the deeply virtual Compton scattering amplitude in QCD, up to power suppressed terms, to all orders in perturbation theory. Furthermore, we show that the virtuality of the produced photon does not influence the general theorem.Comment: 14 pages, Revtex, postscript figures. Improved treatement of "endpoint/breakpoint" regions. Corrected references to earlier wor

Nonforward Parton Distributions

Applications of perturbative QCD to deeply virtual Compton scattering and hard exclusive electroproduction processes require a generalization of usual parton distributions for the case when long-distance information is accumulated in nonforward matrix elements of quark and gluon light-cone operators. We describe two types of nonperturbative functions parametrizing such matrix elements: double distributions F(x,y;t) and nonforward distribution functions F_\zeta (X;t), discuss their spectral properties, evolution equations which they satisfy, basic uses and general aspects of factorization for hard exclusive processes.Comment: Final version, to be published in Phys.Rev.

Hadron Production in Diffractive Deep-Inelastic Scattering

Characteristics of hadron production in diffractive deep-inelastic positron-proton scattering are studied using data collected in 1994 by the H1 experiment at HERA. The following distributions are measured in the centre-of-mass frame of the photon dissociation system: the hadronic energy flow, the Feynman-x (x_F) variable for charged particles, the squared transverse momentum of charged particles (p_T^{*2}), and the mean p_T^{*2} as a function of x_F. These distributions are compared with results in the gamma^* p centre-of-mass frame from inclusive deep-inelastic scattering in the fixed-target experiment EMC, and also with the predictions of several Monte Carlo calculations. The data are consistent with a picture in which the partonic structure of the diffractive exchange is dominated at low Q^2 by hard gluons.Comment: 16 pages, 6 figures, submitted to Phys. Lett.

Measurement of D* Meson Cross Sections at HERA and Determination of the Gluon Density in the Proton using NLO QCD

With the H1 detector at the ep collider HERA, D* meson production cross sections have been measured in deep inelastic scattering with four-momentum transfers Q^2>2 GeV2 and in photoproduction at energies around W(gamma p)~ 88 GeV and 194 GeV. Next-to-Leading Order QCD calculations are found to describe the differential cross sections within theoretical and experimental uncertainties. Using these calculations, the NLO gluon momentum distribution in the proton, x_g g(x_g), has been extracted in the momentum fraction range 7.5x10^{-4}< x_g <4x10^{-2} at average scales mu^2 =25 to 50 GeV2. The gluon momentum fraction x_g has been obtained from the measured kinematics of the scattered electron and the D* meson in the final state. The results compare well with the gluon distribution obtained from the analysis of scaling violations of the proton structure function F_2.Comment: 27 pages, 9 figures, 2 tables, submitted to Nucl. Phys.

Low Q^2 Jet Production at HERA and Virtual Photon Structure

The transition between photoproduction and deep-inelastic scattering is investigated in jet production at the HERA ep collider, using data collected by the H1 experiment. Measurements of the differential inclusive jet cross-sections dsigep/dEt* and dsigmep/deta*, where Et* and eta* are the transverse energy and the pseudorapidity of the jets in the virtual photon-proton centre of mass frame, are presented for 0 < Q2 < 49 GeV2 and 0.3 < y < 0.6. The interpretation of the results in terms of the structure of the virtual photon is discussed. The data are best described by QCD calculations which include a partonic structure of the virtual photon that evolves with Q2.Comment: 20 pages, 5 Figure

A Search for Selectrons and Squarks at HERA

Data from electron-proton collisions at a center-of-mass energy of 300 GeV are used for a search for selectrons and squarks within the framework of the minimal supersymmetric model. The decays of selectrons and squarks into the lightest supersymmetric particle lead to final states with an electron and hadrons accompanied by large missing energy and transverse momentum. No signal is found and new bounds on the existence of these particles are derived. At 95% confidence level the excluded region extends to 65 GeV for selectron and squark masses, and to 40 GeV for the mass of the lightest supersymmetric particle.Comment: 13 pages, latex, 6 Figure

One-Loop Corrections and All Order Factorization In Deeply Virtual Compton Scattering

We calculate the one-loop corrections to a general off-forward deeply-virtual Compton process at leading twist for both parton helicity-dependent and independent cases. We show that the infrared divergences can be factorized entirely into off-forward parton distributions, even when one of the two photons is onshell. We argue that this property persists to all orders in perturbation theory. We obtain the next-to-leading order Wilson coefficients for the general leading-twist expansion of the product of two electromagnetic currents in the \overline{\rm MS} scheme.Comment: Replaced with the version submitted to Phys. Rev.

The Spin Structure of the Nucleon

We present an overview of recent experimental and theoretical advances in our understanding of the spin structure of protons and neutrons.Comment: 84 pages, 29 figure