Molecular monitoring of minimal residual disease in two patients with MLL-rearranged acute myeloid leukemia and haploidentical transplantation after relapse

This report describes the clinical courses of two acute myeloid leukemia patients. Both had MLL translocations, the first a t(10;11)(p11.2;q23) with MLL-AF10 and the second a t(11;19)(q23;p13.1) with MLL-ELL fusion. They achieved a clinical remission under conventional chemotherapy but relapsed shortly after end of therapy. Both had a history of invasive mycoses (one had possible pulmonary mycosis, one systemic candidiasis). Because no HLA-identical donor was available, a haploidentical transplantation was performed in both cases. Using a specially designed PCR method for the assessment of minimal residual disease (MRD), based on the quantitative detection of the individual chromosomal breakpoint in the MLL gene, all patients achieved complete and persistent molecular remission after transplantation. The immune reconstitution after transplantation is described in terms of total CD3+/CD4+, CD3+/CD8+, CD19+, and CD16+/CD56+ cell numbers over time. The KIR and HLA genotypes of donors and recipients are reported and the possibility of a KIR-mediated alloreactivity is discussed. This report illustrates that haploidentical transplantation may offer a chance of cure without chronic graft-versus-host disease in situations where no suitable HLA-identical donor is available even in a high-risk setting and shows the value of MRD monitoring in the pre- and posttransplant setting

STAT3 gain-of-function is not responsible for low total IgE levels in patients with autoimmune chronic spontaneous urticaria

BackgroundThe pathogenesis of chronic spontaneous urticaria (CSU) has not been clarified entirely. Type IIb autoimmune chronic spontaneous urticaria (CSUaiTIIb) is a distinct subtype of CSU that is often difficult to treat and is connected to low levels of total IgE. Previous findings indicate that an enhanced signal transducer and activator of transcription 3 (STAT3) may be responsible for reduced IgE serum levels.ObjectiveOur aim was to investigate a possible underlying gain-of-function mutation or activating polymorphism in STAT3 that could be responsible for the low levels of IgE in patients with CSUaiTIIb.MethodsWe included 10 patients with CSUaiTIIb and low levels of IgE and sequenced selected single nucleotide polymorphisms (SNP) in STAT3 associated with common autoimmune diseases. Exon sequencing was performed for the most relevant exons of STAT3. To test for a gain-of-function of STAT3, we performed a phospho-specific flow cytometry analysis of STAT3 in peripheral blood mononuclear cells before and after stimulation with interleukin-6.ResultsNo differences were found in the prevalence of the tested SNPs between our patients and a control population. Moreover, we could not find any mutations or variants on the tested exons of STAT3. The function of STAT3 was also not altered in our patients.ConclusionIn total, we could not find any evidence for our hypothesis that low IgE in patients with CSUaiTIIb is linked to mutations in STAT3 or altered activity of STAT3. Thus, it remains to be discovered what causes the low serum levels of IgE in patients with CSUaiTIIb

Acute myeloid leukemia: negative prognostic impact of early blast persistence can be in part overcome by a later remission prior to post-induction therapy

In acute myeloid leukemia, there is an ongoing debate on the prognostic value of the early bone marrow assessment in patients receiving intensive therapy. In this retrospective study, we analyzed the prognostic impact of the early response in 1,008 patients with newly diagnosed acute myeloid leukemia, who were treated at our institution with intensive chemotherapy followed by consolidation chemotherapy and/or allogeneic hematopoietic stem cell transplantation (HSCT). We found that early blast persistence has an independent negative prognostic impact on overall survival, eventfree survival and relapse-free survival. This negative prognostic impact may only be overcome in patients showing at least a partial remission at the early bone marrow assessment and who subsequently achieve blast clearance by additional induction chemotherapy prior to consolidation therapy with allogeneic HSCT. In accordance, we propose that the time slope of remission is an additional leukemia-related dynamic parameter that reflects chemosensitivity and thus may inform post-induction therapy decision-making. In addition to patient-related factors, European LeukemiaNet risk group, measurable residual disease monitoring and donor availability, this may particularly apply to European LeukemiaNet intermediate-risk patients, for whom a decision between consolidation chemotherapy and allogeneic HSCT remains challenging in many cases

Nanomechanical control of an optical antenna

Resonant optical nanoantennas hold great promise for applications in physics and chemistry1–6. Their operation relies on their ability to concentrate light on spatial scales much smaller than the wavelength. In this work, we mechanically tune the length and gap between two triangles comprising a single gold bow-tie antenna by precise nanomanipulation with the tip of an atomic force microscope. At the same time, the optical response of the nanostructure is determined by means of dark-field scattering spectroscopy. We find no unique single ‘antenna resonance’. Instead, the plasmon mode splits into two dipole resonances for gap sizes on the order of a few tens of nanometres, governed by the full three-dimensional shape of the antenna arms. This result opens the door to new nano-optomechanical devices, where mechanical changes on the nanometre scale control the optical properties of artificial structures

Autoantibody profiles in microscopic colitis

Fragestellung: Die Ätiologie der mikroskopischen Kolitis ist unklar, diskutiert werden eine Autoimmungenese oder eine medikamentöse Induktion. In einer multizentrischen Querschnittsstudie wurde ein Antikörper-Profil von Patienten mit kollagener und lymphozytärer Kolitis mit dem einer Kontrollgruppe verglichen. Methodik: Bei 26 Patienten mit kollagener und 16 Patienten mit lymphozytärer Kolitis wurden detaillierte anamnestische Daten und ein umfangreiches Autoantikörper-Profil mit den korrelierenden Daten einer Kontrollgruppe von 43 gastroenterologisch Gesunden verglichen. Es wurden Antikörper gegen folgende Strukturen bestimmt: Antinukleäre Antikörper (ANA), antineutrophile cytoplasmatische Antikörper (p-ANCA), Saccharomyces cerevisae (ASCA), intestinale Becherzellen, Pancreasazini, Inselzellen, Gewebe Transglutaminase (TTG), Gliadin, Schilddrüsenmikrosomen (MAK), Glutamatdecarboxylase (GADA) sowie Tyrosinphosphatase (IA-2). Ergebnisse: Patienten mit kollagener und lymphozytärer Kolitis waren signifikant häufiger mit H2-Rezeptorantagonisten und Nicht-steroidalen-Anti-Rheumatika behandelt (p=0,026 und p=0,014). Bei 43% (18/42) bestanden zusätzlich Erkrankungen mit vermuteter Autoimmungenese und/oder Schilddrüsenerkrankungen. Für die kollagene, nicht aber für die lymphozytäre Kolitis ergaben sich gegenüber der Kontrolle signifikant häufiger positive Befunde für ANA (IgG), Gliadin (IgA) sowie ASCA (IGA und IgG). Die kollagene Kolitis war in 15%, die lymphozytäre Kolitis in 13% mit positiven ASCA assoziiert. In der Symptomatik finden sich keine wesentlichen Unterschiede zwischen kollagener- und lymphozytärer Kolitis. Schlußfolgerungen: Die untersuchten Antikörper besitzen keine diagnostische Bedeutung für die mikroskopische Kolitis. Positive ANA und hohe Assoziationen mit Autoimmunerkrankungen wie rheumatoide Arthritis und Sprue könnten ein Hinweis auf eine Autoimmunpathogenese sein. Nicht-steroidale Antirheumatika und H2-Rezeptorantagonisten könnten ebenfalls pathogenetisch bedeutsam sein.Objective: The etiology of microscopic colitis is unclear, an autoimmune response and pharmacological induction have been proposed as possible mechanisms. We conducted a multicentre cross-sectionel study to compare the antibody profiles of patients with collagenous and lymphocytic colitis with those of a control group. Methods: The medical histories and antibody profiles of 26 patients with collagenous and 16 patients with lymphocytic colitis were compared with eachother and the corresponding data of 43 controls without gastroenterological disease. Antibodies of the following structures were determined: antinuclear antibodies (ANA), antineutophil cytoplasmic antibodies (p-ANCA), anti-saccharomyces cerevisiae antibodies (ASCA), intestinal goblet cell antibodies, pancreatic acini, islet cells, tissue transglutaminase (TTG), gliadin, thyroid microsomal antibodies (MAB), glutamate decarboxylase (GADA), tyrosine phosphatase (IA-2). Results: Patients with collagenous and lymphocytic colitis had been treated significantly more often with H2-receptor antgonists and non-steroidal anti-inflammatory drugs (p=0,026 and 0,014, respectively). Additional diseases of presumed autoimmune etiology or thyroid dieseases were present in 43% (18/42) of patients. Compared to the controls we found significantly more positive findings for ANA immunoglobulin G (IgG), gliadin immunoglobulin A (IgA) and ASCA (IgA and IgG) in patients with collagenous colitis but not in those with lymphocytic colitis. Collagenous colitis was associated with positive ASCA in 15% of patients and lymphocytic colitis in 13%. In comparison the data remained do not differ between the subgroups. Conclusions: The autoantibodies investigated are of no diagnostic relevance to microscopic colitis. Positive ANA and strong associations with other autoimmune diseases like rheumatoid arthritis and celiac disease point to an autoimmune etiology. Non-steroidal antiinflamatory drugs and H2-receptor antagonists might also be of pathogentic significance

Atomic force microscope based Kelvin probe measurements : application to an electrochemical reaction

An atomic force microscope (AFM) was utilized as a Kelvin probe to determine work functions of several metals and semiconductors quantitarively. Most of the experimental data show excellent agreement with published values measured by photoemission. Variations in work functions as low as 5 mV could be detected with a typical lateral resolution of 20 nm. This method allowed us to analyze and explain the energetics of an electrochemical reaction on the surface of WSe2, which could be in situ induced and controlled by an externally applied voltage between AFM tip and sample. Thus it could be exploited for etching nanostructures

Kooperative Automation zur Längsführung im urbanen Straßenverkehr

Die Automatisierung der Fahraufgabe kann dazu beitragen, das Fahren sicherer, effizienter und komfortabler zu gestalten. Für verhältnismäßig strukturierte Umgebungen wie Autobahnen ist diese Entwicklung bereits weit fortgeschritten. Adaptive Geschwindigkeitsregelung (ACC), Spurhalteassistent und andere Fahrerassistenzsysteme entlasten den Fahrer dort bereits heute. Die Markteinführung erster Systeme zum hochautomatisierten Fahren auf der Autobahn wird ab 2020 erwartet . Im urbanen Umfeld ist das Verkehrsgeschehen jedoch deutlich komplexer und unstrukturierter. Im Rahmen des Projekts Next Generation Car (NGC) verfolgt das Institut für Verkehrssystemtechnik des DLR mit dem System urbanDRIVE das Ziel einer kooperativen Automation zur längs- und quergeführten Fahrt im urbanen Straßenraum. Als Baustein davon wurde mit urbanDRIVE 1.0 eine Automationsfunktion zur Längsführung entwickelt, prototypisch umgesetzt und im Testfeld AIM im öffentlichen Verkehr in Braunschweig getestet. Der Beitrag erläutert dieses System