251 research outputs found
Targeting self-renewal pathways in myeloid malignancies
A fundamental property of hematopoietic stem cells (HSCs) is the ability to self-renew. This is a complex process involving multiple signal transduction cascades which control the fine balance between self-renewal and differentiation through transcriptional networks. Key activators/regulators of self-renewal include chemokines, cytokines and morphogens which are expressed in the bone marrow niche, either in a paracrine or autocrine fashion, and modulate stem cell behaviour. Increasing evidence suggests that the downstream signaling pathways induced by these ligands converge at multiple levels providing a degree of redundancy in steady state hematopoiesis. Here we will focus on how these pathways cross-talk to regulate HSC self-renewal highlighting potential therapeutic windows which could be targeted to prevent leukemic stem cell self-renewal in myeloid malignancies
Complement deficiencies limit CD20 monoclonal antibody treatment efficacy in CLL
Monoclonal antibodies (MAbs) form a central part of chronic lymphocytic leukaemia (CLL) treatment. We therefore evaluated whether complement defects in CLL patients reduced the induction of complement-dependent cytotoxicity (CDC) by using anti-CD20 MAbs rituximab (RTX) and ofatumumab (OFA). Ofatumumab elicited higher CDC levels than RTX in all CLL samples examined, particularly in poor prognosis cohorts (11qâ and 17pâ). Serum sample analyses revealed that 38.1% of patients were deficient in one or more complement components, correlating with reduced CDC responses. Although a proportion of patients with deficient complement levels initially induced high levels of CDC, on secondary challenge CDC activity in sera was significantly reduced, compared with that in normal human serum (NHS; P<0.01; n=52). In addition, a high CLL cell number contributed to rapid complement exhaustion. Supplementing CLL serum with NHS or individual complement components, particularly C2, restored CDC on secondary challenge to NHS levels (P<0.0001; n=9). In vivo studies revealed that complement components were exhausted in CLL patient sera post RTX treatment, correlating with an inability to elicit CDC. Supplementing MAb treatment with fresh-frozen plasma may therefore maintain CDC levels in CLL patients with a complement deficiency or high white blood cell count. This study has important implications for CLL patients receiving anti-CD20 MAb therapy
Correction: CD93 is expressed on chronic myeloid leukemia stem cells and identifies a quiescent population which persists after tyrosine kinase inhibitor therapy
Correction to: Leukemia
https://doi.org/10.1038/s41375-019-0684-
emission rates in absorptions at rest on Li, Li, Be, C and O
An experimental study of the reaction
on Li, Li, Be, C and O -shell nuclei is
presented. The data were collected by the FINUDA spectrometer operating at the
DANE -factory (LNF-INFN, Italy). Emission rates for the reaction in
the mentioned nuclei are measured and compared with the few existing data. The
spectra of several observables are discussed; indications of Quasi-Free
absorptions by a pair embedded in the nucleus can be obtained from
the study of the missing mass distributions.Comment: Version accepted by PR
A study of the proton spectra following the capture of in Li and C with FINUDA
Momenta spectra of protons emitted following the capture of in Li
and C have been measured with 1% resolution. The C spectrum is
smooth whereas for Li a well defined peak appears at about 500 MeV/. The
first observation of a structure in this region was identified as a strange
tribaryon or, possibly, a -nuclear state. The peak is correlated with a
coming from decay in flight, selected by setting momenta
larger than 275 MeV/. The could be produced, together with a 500
MeV/ proton, by the capture of a in a deuteron-cluster substructure of
the Li nucleus. The capture rate for such a reaction is (1.62\pm
0.23_{stat} ^{+0.71}_{-0.44}(sys))%/K^-_{stop}, in agreement with the existing
observations on He targets and with the hypothesis that the Li nucleus
can be interpreted as a cluster.Comment: 21 pages, 10 figures. Accepted for publication in NP
Proton spectra from Non-Mesonic Weak Decay of p-shell Lambda-Hypernuclei and evidence for the two-nucleon induced process
New spectra from the FINUDA experiment of the Non Mesonic Weak Decay (NMWD)
proton kinetic energy for 9(Lambda)Be, 11(Lambda)B, 12(Lambda)C, 13(Lambda)C,
15 (Lambda)N and 16(Lambda)O are presented and discussed along with the
published data on 5(Lambda)He and 7(Lambda)Li. Exploiting the large mass number
range and the low energy threshold (15 MeV) for the proton detection of FINUDA,
an evaluation of both Final State Interactions (FSI) and the two nucleon
induced NMWD contributions to the decay process has been done. Based on this
evaluation, a linear dependence of FSI on the hypernuclear mass number A is
found and for the two nucleon stimulated decay rate the experimental value of
Gamma2/Gammap=0.43+-0.25 is determined for the first time. A value for the two
nucleon stimulated decay rate to the total decay rate
Gamma2/GammaNMWD=0.24+-0.10 is also extracted.Comment: 11 pages and 2 figure
Production of H and H with the (K,) reaction
The production of neutron rich -hypernuclei via the
(,) reaction has been studied using data collected with the
FINUDA spectrometer at the DANE -factory (LNF). The analysis of the
inclusive momentum spectra is presented and an upper limit for the
production of H and H from Li and Li, is
assessed for the first time.Comment: 11 pages, 3 figures. Accepted for publication in PL
Hypernuclear spectroscopy with K at rest on Li, Be, C and O
The FINUDA experiment collected data to study the production of hypernuclei
on different nuclear targets. The hypernucleus formation occurred through the
strangeness-exchange reaction K^-_{stop} + \; ^AZ \rightarrow \; ^A_{\Lambda}Z
+ \pi^-. From the analysis of the momentum of the emerging , binding
energies and formation probabilities of Li, Be,
C and O have been measured and are here
presented. The behavior of the formation probability as a function of the
atomic mass number A is also discussed.Comment: Accepted for publication in PL
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