Complex Patterns of Chromosome 11 Aberrations in Myeloid Malignancies Target CBL, MLL, DDB1 and LMO2

Exome sequencing of primary tumors identifies complex somatic mutation patterns. Assignment of relevance of individual somatic mutations is difficult and poses the next challenge for interpretation of next generation sequencing data. Here we present an approach how exome sequencing in combination with SNP microarray data may identify targets of chromosomal aberrations in myeloid malignancies. The rationale of this approach is that hotspots of chromosomal aberrations might also harbor point mutations in the target genes of deletions, gains or uniparental disomies (UPDs). Chromosome 11 is a frequent target of lesions in myeloid malignancies. Therefore, we studied chromosome 11 in a total of 813 samples from 773 individual patients with different myeloid malignancies by SNP microarrays and complemented the data with exome sequencing in selected cases exhibiting chromosome 11 defects. We found gains, losses and UPDs of chromosome 11 in 52 of the 813 samples (6.4%). Chromosome 11q UPDs frequently associated with mutations of CBL. In one patient the 11qUPD amplified somatic mutations in both CBL and the DNA repair gene DDB1. A duplication within MLL exon 3 was detected in another patient with 11qUPD. We identified several common deleted regions (CDR) on chromosome 11. One of the CDRs associated with de novo acute myeloid leukemia (P=0.013). One patient with a deletion at the LMO2 locus harbored an additional point mutation on the other allele indicating that LMO2 might be a tumor suppressor frequently targeted by 11p deletions. Our chromosome-centered analysis indicates that chromosome 11 contains a number of tumor suppressor genes and that the role of this chromosome in myeloid malignancies is more complex than previously recognized

Managing hematological cancer patients during the COVID-19 pandemic:an ESMO-EHA Interdisciplinary Expert Consensus

Background: The COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies (HMs), raising questions about the optimal care of this patient group. Methods: This consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of HMs in the COVID-19 pandemic. For this purpose, an international consortium was established including a steering committee, which prepared six working packages addressing significant clinical questions from the COVID-19 diagnosis, treatment, and mitigation strategies to specific HMs management in the pandemic. During a virtual consensus meeting, including global experts and lead by the European Society for Medical Oncology and the European Hematology Association, statements were discussed and voted upon. When a consensus could not be reached, the panel revised statements to develop consensual clinical guidance. Results and conclusion: The expert panel agreed on 33 statements, reflecting a consensus, which will guide clinical decision making for patients with hematological neoplasms during the COVID-19 pandemic.</p

Studying the Underlying Event in Drell-Yan and High Transverse Momentum Jet Production at the Tevatron

We study the underlying event in proton-antiproton collisions by examining the behavior of charged particles (transverse momentum pT > 0.5 GeV/c, pseudorapidity |\eta| < 1) produced in association with large transverse momentum jets (~2.2 fb-1) or with Drell-Yan lepton-pairs (~2.7 fb-1) in the Z-boson mass region (70 < M(pair) < 110 GeV/c2) as measured by CDF at 1.96 TeV center-of-mass energy. We use the direction of the lepton-pair (in Drell-Yan production) or the leading jet (in high-pT jet production) in each event to define three regions of \eta-\phi space; toward, away, and transverse, where \phi is the azimuthal scattering angle. For Drell-Yan production (excluding the leptons) both the toward and transverse regions are very sensitive to the underlying event. In high-pT jet production the transverse region is very sensitive to the underlying event and is separated into a MAX and MIN transverse region, which helps separate the hard component (initial and final-state radiation) from the beam-beam remnant and multiple parton interaction components of the scattering. The data are corrected to the particle level to remove detector effects and are then compared with several QCD Monte-Carlo models. The goal of this analysis is to provide data that can be used to test and improve the QCD Monte-Carlo models of the underlying event that are used to simulate hadron-hadron collisions.Comment: Submitted to Phys.Rev.

Measurement of the W+W−W^+W^- Production Cross Section and Search for Anomalous WWγWW\gamma and WWZWWZ Couplings in ppˉp \bar p Collisions at s=1.96\sqrt{s} = 1.96 TeV

This Letter describes the current most precise measurement of the $W$ boson pair production cross section and most sensitive test of anomalous $WW\gamma$ and $WWZ$ couplings in $p \bar p$ collisions at a center-of-mass energy of 1.96 TeV. The $WW$ candidates are reconstructed from decays containing two charged leptons and two neutrinos, where the charged leptons are either electrons or muons. Using data collected by the CDF II detector from 3.6 fb$^{-1}$ of integrated luminosity, a total of 654 candidate events are observed with an expected background contribution of $320 \pm 47$ events. The measured total cross section is $\sigma (p \bar p \to W^+ W^- + X) = 12.1 \pm 0.9 \textrm{(stat)} ^{+1.6}_{-1.4} \textrm{(syst)}$ pb, which is in good agreement with the standard model prediction. The same data sample is used to place constraints on anomalous $WW\gamma$ and $WWZ$ couplings.Comment: submitted to Phys. Rev. Let

Search for massive resonances decaying in to WW,WZ or ZZ bosons in proton-proton collisions at root s=13 TeV

Peer reviewe

Search for the production of dark matter in association with top-quark pairs in the single-lepton final state in proton-proton collisions at √s=8 TeV

Peer reviewe

Search for vector-like T quarks decaying to top quarks and Higgs bosons in the all-hadronic channel using jet substructure

Peer reviewe

Precise determination of the mass of the Higgs boson and tests of compatibility of its couplings with the standard model predictions using proton collisions at 7 and 8 TeV

Peer reviewe

Search for Technicolor Particles Produced in Association with a W Boson at CDF

submitted to Phys. Rev. LettWe present a search for the technicolor particles $\rho_{T}$ and $\pi_{T}$ in the process $p\bar{p} \to \rho_{T} \to W\pi_{T}$ at a center of mass energy of $\sqrt{s}=1.96 \mathrm{TeV}$. The search uses a data sample corresponding to approximately $1.9 \mathrm{fb}^{-1}$ of integrated luminosity accumulated by the CDF II detector at the Fermilab Tevatron. The event signature we consider is $W\to \ell\nu$ and $\pi_{T} \to b\bar{b}, b\bar{c}$ or $b\bar{u}$ depending on the $\pi_{T}$ charge. We select events with a single high-$p_T$ electron or muon, large missing transverse energy, and two jets. Jets corresponding to bottom quarks are identified with multiple $b$-tagging algorithms. The observed number of events and the invariant mass distributions are consistent with the standard model background expectations, and we exclude a region at 95% confidence level in the $\rho_T$-$\pi_T$ mass plane. As a result, a large fraction of the region $m(\rho_T) = 180$ - $250 \mathrm{GeV}/c^2$ and $m(\pi_T) = 95$ - $145 \mathrm{GeV}/c^2$ is excluded.We present a search for the technicolor particles ρT and πT in the process pp̅ →ρT→WπT at a center of mass energy of √s=1.96  TeV. The search uses a data sample corresponding to approximately 1.9  fb-1 of integrated luminosity accumulated by the CDF II detector at the Fermilab Tevatron. The event signature we consider is W→ℓν and πT→bb̅ , bc̅ or bu̅ depending on the πT charge. We select events with a single high-pT electron or muon, large missing transverse energy, and two jets. Jets corresponding to bottom quarks are identified with multiple b-tagging algorithms. The observed number of events and the invariant mass distributions are consistent with the standard model background expectations, and we exclude a region at 95% confidence level in the ρT-πT mass plane. As a result, a large fraction of the region m(ρT)=180–250  GeV/c2 and m(πT)=95–145  GeV/c2 is excluded.Peer reviewe

Observation of top quark pairs produced in association with a vector boson in pp collisions at s=8 √s=8TeV

Measurements of the cross sections for top quark pairs produced in association with a W or Z boson are presented, using 8 TeV pp collision data corresponding to an integrated luminosity of 19.5 fb −1 , collected by the CMS experiment at the LHC. Final states are selected in which the associated W boson decays to a charged lepton and a neutrino or the Z boson decays to two charged leptons. Signal events are identified by matching reconstructed objects in the detector to specific final state particles from t t ¯ W tt¯W or t t ¯ Z tt¯Z decays. The t t ¯ W tt¯W cross section is measured to be 382 − 102 + 117 fb with a significance of 4.8 standard deviations from the background-only hypothesis. The t t ¯ Z tt¯Z cross section is measured to be 242 − 55 + 65 fb with a significance of 6.4 standard deviations from the background-only hypothesis. These measurements are used to set bounds on five anomalous dimension-six operators that would affect the t t ¯ W tt¯W and t t ¯ Z tt¯Z cross sections