Article
Hematology
Vinothkumar Rajan, Sergey Prykhozhji, Aditya Pandey, Alejandro M. Cohen, Jan K. Rainey, Jason N. Berman
Summary: This study identifies the significant role of the KIT D816V mutation in haematological malignancies and reveals its distinct activation mechanism compared to the wild type, suggesting new targets for therapeutic interventions.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nicole Naumann, Johannes Luebke, Sofie Baumann, Juliana Schwaab, Oliver Hoffmann, Sebastian Kreil, Vito Dangelo, Lukas Reiter, Peter Bugert, Thomas Kristensen, Karl Sotlar, Verena Haselmann, Sven Schneider, Georgia Metzgeroth, Christel Weiss, Henning D. Popp, Alice Fabarius, Wolf-Karsten Hofmann, Nicholas C. P. Cross, Andreas Reiter, Mohamad Jawhar
Summary: The KIT D816V mutation in systemic mastocytosis plays a key role in diagnosis and prognosis. Transcriptional activity of KIT D816V can be used to predict disease severity and patient survival.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Marcelo A. S. de Toledo, Xuhuang Fu, Tiago Maie, Eva M. Buhl, Katrin Goetz, Susanne Schmitz, Anne Kaiser, Peter Boor, Till Braunschweig, Nicolas Chatain, Ivan G. Costa, Tim H. Bruemmendorf, Steffen Koschmieder, Martin Zenke
Summary: In this study, human induced pluripotent stem cells were differentiated into mast cells, which exhibited characteristics of systemic mastocytosis disease. These cells can be used for disease modeling and drug screening.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Marcelo A. S. Toledo, Malrun Gatz, Stephanie Sontag, Karoline Gleixner, Gregor Eisenwort, Kristina Feldberg, Ahmed E. Hamouda, Frederick Kluge, Riccardo Guareschi, Giulia Rossetti, Antonio S. Sechi, Olli M. J. Dufva, Satu M. Mustjoki, Angela Maurer, Herdit M. Schueler, Roman Goetzke, Till Braunschweig, Anne Kaiser, Jens Panse, Mohamad Jawhar, Andreas Reiter, Frank Hilberg, Peter Ettmayer, Wolfgang Wagner, Steffen Koschmieder, Tim H. Bruemmendorf, Peter Valent, Nicolas Chatain, Martin Zenke
Summary: The KIT D816V mutation is a key therapeutic target for systemic mastocytosis, and nintedanib has been identified as a potential inhibitor for KIT D816V in patient-specific pluripotent stem cells.
Article
Hematology
Vanessa E. Kennedy, Cecelia Perkins, Andreas Reiter, Mohamad Jawhar, Johannes Luebke, Hanneke C. Kluin-Nelemans, William Shomali, Cheryl Langford, Justin Abuel, Olivier Hermine, Marek Niedoszytko, Aleksandra Gorska, Andrzej Mital, Patrizia Bonadonna, Roberta Zanotti, Ilaria Tanasi, Mattias Mattsson, Hans Hagglund, Massimo Triggiani, Akif Selim Yavuz, Jens Panse, Deborah Christen, Marc Heizmann, Khalid Shoumariyeh, Sabine Mueller, Chiara Elena, Luca Malcovati, Nicolas Fiorelli, Friederike Wortmann, Vladan Vucinic, Knut Brockow, Christos Fokoloros, Sotirios G. Papageorgiou, Christine Breynaert, Dominique Bullens, Michael Doubek, Anja Ilerhaus, Irena Angelova-Fischer, Oleksii Solomianyi, Judit Varkonyi, Vito Sabato, Axel Ruefer, Tanja Daniela Schug, Maud A. W. Hermans, Anna Belloni Fortina, Francesca Caroppo, Horia Bumbea, Theo Gulen, Karin Hartmann, Hanneke Oude Elberink, Juliana Schwaab, Michel Arock, Peter Valent, Wolfgang R. Sperr, Jason Gotlib
Summary: This study evaluated 92 patients with mast cell leukemia (MCL) and found that 34% of patients had an associated hematologic neoplasm. Some patients had chronic MCL, while a small percentage had leukemic MCL. The study also identified genetic mutations and treatment strategies that were associated with prognosis.
Article
Oncology
Lina Degenfeld-Schonburg, Susanne Gamperl, Gabriele Stefanzl, Anna-Katharina Schruef, Irina Sadovnik, Karin Bauer, Dubravka Smiljkovic, Gregor Eisenwort, Barbara Peter, Georg Greiner, Emir Hadzijusufovic, Juliana Schwaab, Wolfgang R. Sperr, Gregor Hoermann, Sonja Kopanja, Zsolt Szepfalusi, Konrad Hoetzenecker, Peter Jaksch, Andreas Reiter, Michel Arock, Peter Valent
Summary: Systemic mastocytosis (SM) is a complex hematopoietic neoplasm with clinical symptoms caused by organ infiltration by mast cells (MC) and the release of pro-inflammatory mediators. The growth and survival of MC in SM are triggered by various oncogenic mutant forms of the tyrosine kinase KIT, including the prevalent variant D816V. Two novel drugs, avapritinib and nintedanib, were found to effectively inhibit the growth and survival of neoplastic MC expressing different KIT mutant forms, including D816V, V560G, and K509I, making them potential candidates for the treatment of advanced SM.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Article
Immunology
Geethani Bandara, Guido H. Falduto, Andrea Luker, Yun Bai, Annika Pfeiffer, Justin Lack, Dean D. Metcalfe, Ana Olivera
Summary: The HMC-1.2 cell line expresses two oncogenic mutations, while the HMC-1.3 cell line expresses only one oncogenic mutation. The HMC-1.3 cells are more sensitive to interventional drugs and have increased tumorigenicity, suggesting they may serve as an improved preclinical model for mastocytosis.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Mariarita Sciume, Giusy Ceparano, Cristina Eller-Vainicher, Sonia Fabris, Silvia Lonati, Giorgio Alberto Croci, Luca Baldini, Federica Irene Grifoni
Summary: Systemic mastocytosis (SM) is a rare neoplasm with heterogeneous clinical features, requiring individualized treatment. A patient with indolent SM developed a myeloid neoplasm with PDGFRA rearrangement, achieving complete remission with low-dose imatinib treatment.
FRONTIERS IN ONCOLOGY
(2021)
Article
Hematology
Nicole Naumann, Johannes Lubke, William Shomali, Lukas Reiter, Hans-Peter Horny, Mohamad Jawhar, Vito Dangelo, Alice Fabarius, Georgia Metzgeroth, Sebastian Kreil, Karl Sotlar, Claire Oni, Claire Harrison, Wolf-Karsten Hofmann, Nicholas C. P. Cross, Peter Valent, Deepti Radia, Jason Gotlib, Andreas Reiter, Juliana Schwaab
Summary: 45 patients with myeloid neoplasms and concurrent JAK2 V617F and KIT D816V mutations were studied, showing overlapping clinical features and discordant development of variant allele frequency for both mutations. The overall survival of patients without additional high-risk mutations was 77% at 5 years, indicating a fundamentally different prognosis compared to the impact of additional mutations in the individual disorders.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Pathology
Peter Valent, Cem Akin, Wolfgang R. Sperr, Hans-Peter Horny, Michel Arock, Dean D. Metcalfe, Stephen J. Galli
Summary: Mastocytosis is a group of heterogeneous neoplasms characterized by an increase and accumulation of clonal mast cells in various organ systems. It can present as cutaneous mastocytosis or systemic mastocytosis, and the latter is further divided into different variants based on histopathological and molecular features, clinical variables, and organ involvement. The oncogenic machinery triggered by mutant forms of KIT plays a key role in MC expansion and disease progression, and genetic background, somatic mutations, and comorbidities also contribute to the course and prognosis. This article provides an update on the genetics, etiology, and pathology of mastocytosis, focusing on diagnostic criteria and new treatment concepts.
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE
(2023)
Article
Hematology
Andreas Reiter, Juliana Schwaab, Daniel J. DeAngelo, Jason Gotlib, Michael W. Deininger, Kristen M. Pettit, Ivan Alvarez-Twose, Alessandro M. Vannucchi, Jens Panse, Uwe Platzbecker, Olivier Hermine, Ingunn Dybedal, Hui-Min Lin, Svetlana N. Rylova, Katrin Ehlert, Sasa Dimitrijevic, Deepti H. Radia
Summary: Avapritinib has shown high efficacy and safety in patients with AdvSM who had received prior systemic therapy, leading to significant clinical responses in the majority of patients with improvements in various growth indicators.
Article
Allergy
Merel C. Onnes, Abdulrazzaq Alheraky, Martijn C. Nawijn, Tim E. Sluijter, Andre B. Mulder, Suzanne Arends, Hanneke N. G. Oude Elberink
Summary: In patients with normal bsT and grade IV WVA, the REMA score is a relatively reliable method for detecting those at risk of CMD. KIT mutation analysis in peripheral blood can serve as an additional screening method in patients with low REMA scores.
CLINICAL AND TRANSLATIONAL ALLERGY
(2022)
Article
Oncology
Ruben A. Mesa, Erin M. Sullivan, David Dubinski, Brittany Carroll, Valerie M. Slee, Susan Jennings, Celeste C. Finnerty, Linda S. Bohannon, Susan D. Mathias, Betsy J. Lahue, Mariana C. Castells
Summary: This study examined the perceptions and management strategies of US health care providers treating systemic mastocytosis (SM). Most patients were found to have nonadvanced disease, but symptoms significantly disrupted their lives. Physicians estimated that SM is diagnosed within months of symptom onset, contrary to previous reports of longer delays.
Article
Allergy
Leander P. De Puysseleyr, Didier G. Ebo, Jessy Elst, Margaretha A. Faber, Marie-Line Van der Poorten, Athina L. Van Gasse, Chris H. Bridts, Christel Mertens, Michel Van Houdt, Margo M. Hagendorens, Anke Verlinden, Katrien Vermeulen, Marie-Berthe Maes, Zwi N. Berneman, Vito Sabato
Summary: In patients with severe anaphylaxis but no mastocytosis in the skin and baseline serum tryptase less than 30 ng/mL, detection of the KIT D816V mutation in peripheral blood may not be very helpful in diagnosing primary mast cell disorders.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2021)
Article
Dermatology
Yuka Shibata, Seiichi Hirota, Ikuo Saito, Akihiko Asahina
Summary: DCM is the least common subtype of cutaneous mastocytosis and is generally more severe. This case suggests that spontaneous resolution can be expected in DCM even after a long period of time, and that serum tryptase level serves as a good surrogate marker to monitor the clinical course.
JOURNAL OF DERMATOLOGY
(2021)
Article
Oncology
Kerstin Maria Kampa-Schittenhelm, Olaf Salitzky, Figen Akmut, Barbara Illing, Lothar Kanz, Helmut Rainer Salih, Marcus Matthias Schittenhelm
Article
Biochemistry & Molecular Biology
Kerstin Maria Kampa-Schittenhelm, Michael Charles Heinrich, Figen Akmut, Katharina Henriette Rasp, Barbara Illing, Hartmut Doehner, Konstanze Doehner, Marcus Matthias Schittenhelm
Article
Oncology
Matthew R. Kearney, Emerson Y. Chen, Gina M. Vaccaro, John Strother, Andrea Burt, Kendra Todd, Jeff Donovan, Kerstin M. Kampa-Schittenhelm, Charles D. Lopez
ANTICANCER RESEARCH
(2019)
Article
Medicine, General & Internal
Marcus Matthias Schittenhelm, Bianca Walter, Vasileia Tsintari, Birgit Federmann, Mihada Bajrami Saipi, Figen Akmut, Barbara Illing, Ulrike Mau-Holzmann, Falko Fend, Charles Darin Lopez, Kerstin Maria Kampa-Schittenhelm
Article
Medicine, General & Internal
K. M. Kampa-Schittenhelm, T. Haverkamp, M. Bonin, V Tsintari, H. J. Buehring, L. Haeusser, G. Blumenstock, S. T. Dreher, T. Ganief, F. Akmut, B. Illing, U. A. Mau-Holzmann, I Bonzheim, E. Schleicher, W. Vogel, M. M. Schittenhelm
Article
Medicine, General & Internal
Johannes Kliebhan, Andrej Besse, Kerstin Kampa-Schittenhelm, Marcus Schittenhelm, Christoph Driessen
Summary: The p53_R273H mutation leads to increased glucose uptake, lactic acidosis, and accelerated tumor growth in tumor cells. We present a case of mantle cell lymphoma with this mutation, characterized by severe lactic acidosis, hypoglycemia, and aggressive disease.
CLINICAL CASE REPORTS
(2022)
Meeting Abstract
Hematology
Marcus M. Schittenhelm, Max Kaiser, Gunnar Blumenstock, Kerstin Maria Kampa-Schittenhelm
Meeting Abstract
Hematology
Kerstin Maria Kampa-Schittenhelm, Ulrike Mau-Holzmann, Charles Lopez, Marcus M. Schittenhelm
Meeting Abstract
Hematology
Kerstin Maria Kampa-Schittenhelm, Hans-Joerg Buehring, Michael Bonin, Wichard Vogel, Lothar Kanz, Thomas Haverkamp, Marcus M. Schittenhelm
Meeting Abstract
Hematology
Marcus M. Schittenhelm, Figen Akmut, Barbara Illing, Julia Frey, Katja Schuster, Abhijit Ramachandran, Lothar Kanz, Kerstin M. Kampa-Schittenhelm
Meeting Abstract
Hematology
Kerstin M. Kampa-Schittenhelm, Figen Akmut, Barbara Illing, Charles Lopez, Marcus M. Schittenhelm
Meeting Abstract
Hematology
Kerstin M. Kampa-Schittenhelm, Barbara Illing, Figen Akmut, Michael Walter, Charles D. Lopez, Marcus M. Schittenhelm