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Articles by Michael Heuser
Clinical and molecular characteristics of FLT3 -ITD microclones in elderly patients with acute myeloid leukemia receiving less-intensive therapy
To the Editor, Internal tandem duplications (ITD) of the FMS-like Tyrosinkinase 3 (FLT3) are detected in up to 30% of all newly diagnosed acute myeloid leukemia (AML) cases, with a decreasing prevalence in elderly patients [1]. FLT3-ITD positivity in AML patients predicts poor prognosis and shorter median overall survival (OS), corresponding to an intermediate genetic risk classification per the ELN 2024 less-intensive score [2].
Retroperitoneal bulk predicts chylothorax in follicular lymphoma–control requires systemic response
To the Editor Lymphoma-associated non-traumatic chylothorax (NTC) is defined as the accumulation of triglyceride-rich pleural fluid (>1.24 mmol/L) due to a lymphoproliferative disorder [1]. It may cause dyspnea, respiratory failure, increase the risk of infections such as pleural empyema, and exacerbate malnutrition [2].
Initial leukemic epigenomic state determines hypomethylating agent response
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Abstract Hypomethylating agents (HMAs) are a mainstay of therapy for myeloid cancers, but genetic biomarkers do not predict who will respond to treatment.
By Derek Tam, Franziska Mey, Diana Lin, Christina May, Jihong Jiang, Joshua Bridgers, Kieran O’Neill, Frederick Vizeacoumar, Charles Craddock, Paresh Vyas, Luca Malcovati, Rena Buckstein, Michelle Moksa, Martin Hirst, Franco J. Vizeacoumar, Nadia Medvedev, Michael Heuser, Ryan J. Stubbins, Yu Deng, Aly Karsan, Aparna Gopal, Brett Caswell, Mackenzie MacAuley, Emilie Haniak
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Nature
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Unravelling co-mutational patterns with prognostic implications in NPM1 mutated adult acute myeloid leukemia – a HARMONY study - Leukemia
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Abstract NPM1-mutated (NPM1-mut) acute myeloid leukemia (AML) is generally associated with a more favorable outcome, although the presence of additional gene mutations can influence patient prognosis. We analyzed intensively-treated adult NPM1-mut AML patients included in the HARMONY Alliance database.
By Alberto Hernández-Sánchez, Ángela Villaverde Ramiro, Amin T. Turki, Jurjen Versluis, Javier Martinez Elicegui, Gastone Castellani, Jesse M. Tettero, Joaquín Martínez-López, Ken Mills, Guillermo Sanz, Maria Teresa Voso, Christoph Röllig, Christian Thiede, Klaus H. Metzeler, Konstanze Döhner, Michael Heuser, Torsten Haferlach, Brian J. Huntly, Hartmut Döhner, Raúl Azibeiro, Rabea Mecklenbrauck, Peter JM Valk, Jesús María Hernández-Rivas
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Nature
Verified
Differential prognostic impact of myelodysplasia-related gene mutations in a European cohort of 4978 intensively treated AML patients - Leukemia
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By Marius Bill, Jan-Niklas Eckardt, Christian Rausch, Klaus H. Metzeler, Karsten Spiekermann, Sebastian Stasik, Alexander A. Wurm, Ulf Schnetzke, Andreas Hochhaus Verified, Bernhard Wörmann, Hermann Einsele, Dennis Görlich, Andreas Burchert, Christoph Schliemann, Stefan Krause, Maher Hanoun, Johannes Schetelig, Jan Moritz Middeke, Lars Bullinger, Michael Heuser, Felicitas Thol, Claudia D. Baldus, Carsten Müller-Tidow, Jan Valka, Barbora Weinbergerova, Pierre-Yves Dumas, Sarah Bertoli, Eric Delabesse, Christian Récher, Arnaud Pigneux, Tobias Herold, Maximillian-Alexander Röhnert
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Nature
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Genetic and epigenetic alterations at secondary resistance after continued decitabine-based treatment of acute myeloid leukemia in the randomized phase II DECIDER trial | Leukemia
Therapies containing the hypomethylating agents (HMA) decitabine (DEC) or azacitidine (AZA) are standard of care for patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. However, initially responsive disease eventually develops secondary resistance [1,2,3,4].
Base edited “universal” donor CAR T-cell strategies for acute myeloid leukaemia - Leukemia
Abstract Acute myeloid leukaemia (AML) is often aggressive and life-threatening with limited curative options. Immunotherapies including chimeric antigen receptor (CAR) T-cell approaches are under investigation, but high levels of disease heterogeneity remain a major hurdle to achieving durable responses. Targeting of multiple antigens may ensure complete immunological coverage of leukaemic blast populations, but such antigens are often also present on healthy haematopoietic populations.
Real-world experience with first-line CPX-351 treatment in patients with acute myeloid leukemia – long-term follow-up with focus on younger patients - Blood Cancer Journal
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Although the pivotal phase-3 trial establishing CPX-351 as standard of care for therapy-related AML (tAML) or AML with myelodysplasia-related changes (AML-MRC) was performed only in patients aged 60–75 years [1, 2], it is approved for adults without age limit. Still, limited data resulted in restrictive recommendations regarding its use in younger patients (<60 years) by national and international guidelines [3].
By Jan Moritz Middeke, Christoph Röllig, Matthias Stelljes, Verena I. Gaidzik, Katrin Koch, Felicitas Thol, Stefan Krause, Vladan Vucinic, Michael Heuser, Guido Kobbe, Nael Alakel, Malte von Bonin, Katja Sockel, Maher Hanoun, Katharina Götze, Eva Wagner-Drouet, Konstanze Döhner, Hartmut Döhner, Christoph Schliemann, Johannes Schetelig, Thomas Schroeder, Charlotte Neuerburg, Sara Flossdorf
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Nature
Verified
Bemcentinib as monotherapy and in combination with low-dose cytarabine in acute myeloid leukemia patients unfit for intensive chemotherapy: a phase 1b/2a trial | Nature Communications
Abstract Beyond first line, the prognosis of relapsed/refractory (R/R) acute myeloid leukemia (AML) patients is poor with limited treatment options. Bemcentinib is an orally bioavailable, potent, highly selective inhibitor of AXL, a receptor tyrosine kinase associated with poor prognosis, chemotherapy resistance and decreased antitumor immune response.
Dose-Reduced FLA-IDA in Combination with Venetoclax Is an Effective and Safe Salvage Therapy in Relapsed and Refractory Acute Myeloid Leukemia (R/R AML)
All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited. For more information, please refer to https://www.mdpi.com/openaccess.
Müssen wir für die Rente alle länger arbeiten?
Microsoft tritt für den Schutz Ihrer Privatsphäre ein. Microsoft und unsere Drittanbieter verwenden Cookies, um Informationen wie eindeutige IDs zu speichern und darauf zuzugreifen, um unsere Dienste und Anzeigen bereitzustellen, zu pflegen und zu verbessern. Wenn Sie zustimmen, personalisieren MSN und Microsoft Bing die angezeigten Inhalte und Anzeigen.
Schwächelnde Wirtschaft: Müssen wir für die Rente länger arbeiten?
„It’s the economy, stupid!“ (dt: „Es ist immer die Wirtschaft, Dummkopf!“) Mit diesem Slogan gewann Bill Clinton 1992 die amerikanische Präsidentschaft. Seine Botschaft: Was wir uns als Gesellschaft leisten wollen, muss von einer robusten Wirtschaft erarbeitet werden. Das trifft fraglos auch auf unser – zunehmend notleidendes – gesetzliches Rentensystem zu. Fundament seiner langfristigen Stabilität ist eine leistungsfähige Wirtschaft.
Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications – a HARMONY study - Leukemia
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Abstract Balanced rearrangements involving the KMT2A gene (KMT2Ar) are recurrent genetic abnormalities in acute myeloid leukemia (AML), but there is lack of consensus regarding the prognostic impact of different fusion partners. Moreover, prognostic implications of gene mutations co-occurring with KMT2Ar are not established. From the HARMONY AML database 205 KMT2Ar adult patients were selected, 185 of whom had mutational information by a panel-based next-generation sequencing analysis.
By Alberto Hernández-Sánchez, Gastone Castellani, Ángela Villaverde Ramiro, Klaus H. Metzeler, Jesse M. Tettero, Joaquín Martínez-López, Javier Martinez Elicegui, Ken Mills, Christian Thiede, Guillermo Sanz, Konstanze Döhner, Michael Heuser, Torsten Haferlach, Amin T. Turki, Brian J. Huntly, Hartmut Döhner
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Nature
Verified
Anti-T-lymphocyte globulin improves GvHD-free and relapse-free survival in myelofibrosis after matched related or unrelated donor transplantation - Bone Marrow Transplantation
Abstract Acute and chronic graft-versus-host disease (GvHD) are major complications of allogeneic hematopoietic cell transplantation (alloHCT). In vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG) as part of the conditioning regimen prior to alloHCT is frequently used as GvHD prophylaxis, but data on its role in myelofibrosis is scarce. We took advantage of an international collaborative network to investigate the impact of ATLG in myelofibrosis undergoing first alloHCT.
Finanzen: Sind Geldgeschenke zu Weihnachten eine gute Idee?
Hurra, der Advent ist da. Für viele bedeutet das auch: Es werden wieder Geschenke gekauft, und zwar nicht zu knapp. Im Durchschnitt wollen die Menschen in diesem Jahr zwischen 250 und 300 Euro für Weihnachtsgeschenke ausgeben, insgesamt über 18 Milliarden Euro. Natürlich wieder für die Klassiker auf dem Gabentisch: Spielwaren, Kleidung, Bücher, Kosmetik, Schmuck, Unterhaltungselektronik. Und auf der Beliebtheitsskala seit einigen Jahren ganz vorn dabei: Geldgeschenke. Zu Recht, wie ich finde.
Finanzen: Ist mein Geld in Immobilien noch sicher?
Sie waren lange Zeit DIE Anlage für Menschen, die im Alter gut abgesichert sein wollten: Immobilien, selbst genutzt oder vermietet und pünktlich zur Rente abbezahlt. Doch nach den Jahren des Aufschwungs stehen am Immobilienmarkt viele Zeichen auf Sturm. Gestiegene Zinsen und zunehmende staatliche Regelung, etwa bei Energievorschriften, verunsichern (angehende) Immobilienbesitzer. Sollte man jetzt trotzdem noch kaufen? Experten geben eine ganz klare Antwort.
Cell fate determinant Llgl1 is required for propagation of acute myeloid leukemia - Leukemia
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Abstract Scribble complex proteins can influence cell fate decisions and self-renewal capacity of hematopoietic cells. While specific cellular functions of Scribble complex members are conserved in mammalian hematopoiesis, they appear to be highly context dependent. Using CRISPR/Cas9-based genetic screening, we have identified Scribble complex-related liabilities in AML including LLGL1.
By Michael Heuser, Andreas Hochhaus Verified, Steven Lane, Sarah Graessle, Arik Horne, Franziska Bemmann
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Nature
Verified
Impact of disease burden on clinical outcomes of AML patients receiving allogeneic hematopoietic cell transplantation: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation | Bone Marrow Transplantation
Authors and Affiliations Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon Iman Abou Dalle & Ali Bazarbachi Department of Haematology, Hopital Saint-Antoine, INSERM, Paris, France Myriam Labopin & Mohamad Mohty Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Nicolaus Kröger Dept.
In vivo kinetics of early, non-random methylome and transcriptome changes induced by DNA-hypomethylating treatment in primary AML blasts - Leukemia
Abstract Despite routine use of DNA-hypomethylating agents (HMAs) in AML/MDS therapy, their mechanisms of action are not yet unraveled. Pleiotropic effects of HMAs include global methylome and transcriptome changes. We asked whether in blasts and T-cells from AML patients HMA-induced in vivo demethylation and remethylation occur randomly or non-randomly, and whether gene demethylation is associated with gene induction.
Nanoparticle-mediated targeting of the fusion gene RUNX1/ETO in t(8;21)-positive acute myeloid leukaemia - Leukemia
Abstract A hallmark of acute myeloid leukaemias (AMLs) are chromosomal rearrangements that give rise to novel leukaemia-specific fusion genes. Most of these fusion genes are both initiating and driving events in AML and therefore constitute ideal therapeutic targets but are challenging to target by conventional drug development. siRNAs are frequently used for the specific suppression of fusion gene expression but require special formulations for efficient in vivo delivery.
Das liebe Geld: Deshalb lohnt sich jetzt die Kapitallebensversicherung
Die Kapitallebensversicherung ist ein Multitalent: Absicherung der Familie im Todesfall, eigene Altersvorsorge im Erlebensfall - häufig wahlweise als ordentlicher Batzen Geld oder als lebenslange monatliche Zusatzrente. Lesen Sie mit BILDplus, warum jetzt der Abschluss der Versicherung lohnt.
A new player in IDH1 mutated myeloid neoplasias
Acute myeloid leukaemia with mutated IDH1 is most frequently found in the European LeukemiaNet intermediate risk group.
Modified risk-stratified sequential treatment (subcutaneous rituximab with or without chemotherapy) in B-cell Post-transplant lymphoproliferative disorder (PTLD) after Solid organ transplantation (SOT): the prospective multicentre phase II PTLD-2 trial |
Abstract The prospective multicentre Phase II PTLD-2 trial (NCT02042391) tested modified risk-stratification in adult SOT recipients with CD20-positive PTLD based on principles established in the PTLD-1 trials: sequential treatment and risk-stratification. After rituximab monotherapy induction, patients in complete remission as well as those in partial remission with IPI < 3 at diagnosis (low-risk) continued with rituximab monotherapy and thus chemotherapy free.
Genomic landscape of patients with FLT3-mutated acute myeloid leukemia (AML) treated within the CALGB 10603/RATIFY trial - Leukemia
Abstract The aim of this study was to characterize the mutational landscape of patients with FLT3-mutated acute myeloid leukemia (AML) treated within the randomized CALGB 10603/RATIFY trial evaluating intensive chemotherapy plus the multi-kinase inhibitor midostaurin versus placebo.
Ivosidenib and Azacitidine in IDH1-Mutated Acute Myeloid Leukemia
Related Articles Abstract Background The combination of ivosidenib — an inhibitor of mutant isocitrate dehydrogenase 1 (IDH1) — and azacitidine showed encouraging clinical activity in a phase 1b trial involving patients with newly diagnosed IDH1-mutated acute myeloid leukemia. Methods Download a PDF of the Research Summary.
Ivosidenib and Azacitidine in IDH1-Mutated Acute Myeloid Leukemia
Article Figures/Media Metrics Related Articles Abstract Background The combination of ivosidenib — an inhibitor of mutant isocitrate dehydrogenase 1 (IDH1) — and azacitidine showed encouraging clinical activity in a phase 1b trial involving patients with newly diagnosed IDH1-mutated acute myeloid leukemia.
Weltklimarat (IPCC): Nachhaltigkeit ist Megatrend in der Geldanlage
Im August 2021 nahm sich die Fridays-for-Future-Bewegung in Frankfurt die Finanzbranche vor: „Wenn die Erde eine Bank wäre, hättet ihr sie schon längst gerettet.“ Nach Meinung der Bewegung spielt die Finanzbranche eine Rolle, wenn nicht gar eine Schlüsselrolle beim Umbau der Wirtschaft in Richtung Nachhaltigkeit – konkret mithilfe der sogenannten ESG-Kriterien: In Finanzprodukten müssten die Belange von Umwelt (Environmental), Menschen und Gesellschaft (Social) und verantwortungsvollem...
Germline variants drive myelodysplastic syndrome in young adults
Fig. 1: Incidence and variation in age of onset by causal gene. References 1. Churpek JE, Pyrtel K, Kanchi K-L, Shao J, Koboldt D, Miller CA, et al. Genomic analysis of germ line and somatic variants in familial myelodysplasia/acute myeloid leukemia. Blood. 2015;126:2484–90. CAS Article Google Scholar 2. Guidugli L, Johnson AK, Alkorta-Aranburu G, Nelakuditi V, Arndt K, Churpek JE, et al.
Safety and efficacy of BAY1436032 in IDH1-mutant AML: phase I study results
Abstract The mutant IDH1 (mIDH1) inhibitor BAY1436032 demonstrated robust activity in preclinical AML models, supporting clinical evaluation. In the current dose-escalation study, BAY1436032 was orally administered to 27 mIDH1 AML subjects across 4 doses ranging from 300 to 1500 mg twice-daily. BAY1436032 exhibited a relatively short half-life and apparent non-linear pharmacokinetics after continuous dosing.
Effective drug treatment identified by in vivo screening in a transplantable patient-derived xenograft model of chronic myelomonocytic leukemia
Abstract To establish novel and effective treatment combinations for chronic myelomonocytic leukemia (CMML) preclinically, we hypothesized that supplementation of CMML cells with the human oncogene Meningioma 1 (MN1) promotes expansion and serial transplantability in mice, while maintaining the functional dependencies of these cells on their original genetic profile.
Message from the void: MRD analysis from ctDNA
Michael Heuser and Courteney K. Lai Blood 2019 133:2631-2633; doi: https://doi.org/10.1182/blood-2019-04-901181 To view this item, select one of the options below. If you already have a subscription, you may gain access using your ASH username and password. If you are a Librarian or institutional account administrator you can use this link to manage your account and view usage reports.
Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party
Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party Gerrit J. Schuurhuis, Michael Heuser, Sylvie Freeman, Marie-Christine Béné, Francesco Buccisano, Jacqueline Cloos, David Grimwade, Torsten Haferlach, Robert K. Hills, Christopher S. Hourigan, Jeffrey L. Jorgensen, Wolfgang Kern, Francis Lacombe, Luca Maurillo, Claude Preudhomme, Bert A. van der Reijden, Christian Thiede, Adriano Venditti, Paresh Vyas, Brent L. Wood, Roland B.
Clinical Impact of KMT2C and SPRY4 Expression Levels in Intensively Treated Younger Adult Acute Myeloid Leukemia Patients
To evaluate the prognostic impact of gene expression levels (ELs) of two tumor suppressor genes, sprouty 4 (SPRY4, located on 5q) and lysine methyltransferase 2C (KMT2C, located on 7q) in correlation to clinical characteristics and genetic abnormalities assessed at initial diagnosis in acute myeloid leukemia (AML). Gene expression levels were measured on cDNA by RT-qPCR from diagnostic bone marrow samples of 275 intensively treated adult AML patients (median age, 48 years).
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