Article
Oncology
Hannah J. Uckelmann, Elena L. Haarer, Reina Takeda, Eric M. Wong, Charlie Hatton, Christian Marinaccio, Florian Perner, Masooma Rajput, Noa J. C. Antonissen, Yanhe Wen, Lu Yang, Lorenzo Brunetti, Chun -Wei Chen, Scott A. Armstrong
Summary: The dysregulation of developmental and stem cell-associated genes is a common phenomenon during cancer development. Most patients with acute myeloid leukemia (AML) express high levels of HOXA cluster genes and MEIS1, with an NPM1 mutation (NPM1c) being common in these cases. This study reveals that NPM1c directly binds to specific chromatin targets, collaborates with the MLL1 complex, and directly regulates oncogenic gene expression in AML.
Review
Biochemistry & Molecular Biology
Carmine Liberatore, Mauro Di Ianni
Summary: The management of relapsed acute myeloid leukemia (AML) post allogeneic hematopoietic stem cell transplantation (HSCT) remains a clinical challenge. Hypomethylating agents (HMAs) have become the standard therapeutic approach due to favorable tolerability and their ability to be combined with other anti-leukemic agents. The addition of donor lymphocytes infusions (DLI) generally leads to improved outcomes, while the introduction of novel targeted drugs offers new possibilities in salvage regimens.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Xue Qing David Wang, Dandan Fan, Qinyu Han, Yiman Liu, Hongzhi Miao, Xinyu Wang, Qinglan Li, Dong Chen, Haley Gore, Pamela Himadewi, Gerd P. Pfeifer, Tomasz Cierpicki, Jolanta Grembecka, Jianzhong Su, Shasha Chong, Liling Wan, Xiaotian Zhang
Summary: Nucleophosmin (NPM1) is a nucleolar protein with various functions, and its mutation is commonly found in acute myeloid leukemia (AML). This study shows that mutant NPM1 directly binds to active chromatin regions and controls the transcription of AML-driving genes. These findings provide insights into the mechanism behind AML caused by NPM1 mutation and suggest potential therapeutic interventions.
Review
Immunology
Justin Loke, Richard Buka, Charles Craddock
Summary: While most AML patients achieve complete remission with intensive chemotherapy, many face a risk of relapse if treated with chemotherapy alone. Allogeneic stem cell transplant has become a key treatment strategy for AML patients, especially for those in first complete remission and advanced stages. Despite a decrease in transplant-related mortality, there remains a need to address the risk of disease relapse.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Hematology
Brunangelo Falini
Summary: The importance and relevance of NPM1 mutations in AML, including their involvement in chromatin-level regulation and gene expression, as well as their implications for classification and potential targeted therapies.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Review
Oncology
Li Xuan, Qifa Liu
Summary: Relapse is still the main reason for treatment failure in AML patients undergoing allo-HSCT. Evidence suggests that maintenance therapy post-transplantation, particularly targeted drugs like hypomethylating agents, FLT3 inhibitors, and isocitrate dehydrogenase inhibitors, could benefit AML patients, especially those at high risk.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Lynn Chin, Chantelle Ye Gwen Wong, Harinder Gill
Summary: Mutations in the NPM1 gene are commonly found in AML patients, and this review explores various molecular methods for monitoring minimal residual disease (MRD) in NPM1-mutated AML. It also discusses current and potential drug therapies, as well as targeted strategies for aberrant NPM1 pathways and epigenetic regulation. The effects of stress on AML presentation and the advancement of immunotherapy are also mentioned.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Weijia Fu, Aijie Huang, Lili Xu, Yanni Peng, Lei Gao, Li Chen, Jie Chen, Gusheng Tang, Jianmin Yang, Xiong Ni
Summary: Cytogenetic abnormalities are significantly associated with a worse prognosis in NPM1(mut) acute myeloid leukemia (AML) patients, and patients who undergo alloHSCT have longer survival.
LEUKEMIA & LYMPHOMA
(2022)
Review
Oncology
Desiree Kunadt, Friedrich Stoelzel
Summary: The number of patients receiving allogeneic hematopoietic stem cell transplantation (alloHCT) has been increasing due to advances in transplant technology, supportive care, transplant safety, and donor availability. Acute myeloid leukemia (AML) is the most common indication for alloHCT, but disease relapse remains a major challenge. Maintaining a strong graft-versus-leukemia (GvL) effect is crucial for patient prognosis and long-term survival.
CANCER MANAGEMENT AND RESEARCH
(2021)
Article
Genetics & Heredity
Alessandra Venanzi, Roberta Rossi, Giovanni Martino, Ombretta Annibali, Giuseppe Avvisati, Maria Grazia Mameli, Paolo Sportoletti, Enrico Tiacci, Brunangelo Falini, Maria Paola Martelli
Summary: NPM1 mutations in AML primarily occur in exon 12, leading to changes at the C-terminus, including the creation of a new nuclear export signal (NES). Various methods, such as IHC, molecular sequencing, and WB with specific antibodies, can be used to identify NPM1-mutated AML. A novel combination of two mutations involving exon 12 was discovered, one of which was not identified by WB.
Article
Hematology
Sanam Shahid, Nicholas Ceglia, Jean-Benoit Le Luduec, Andrew Mcpherson, Barbara Spitzer, Theodota Kontopoulos, Viktoria Bojilova, M. Kazim Panjwani, Mikhail Roshal, Sohrab P. Shah, Omar Abdel-Wahab, Benjamin Greenbaum, Katharine C. Hsu
Summary: This study investigated the effects of allo-HCT on AML cells using a novel single-cell proteogenomic approach. The results demonstrated immune-related transcriptional signatures in posttransplant relapses, revealing dysfunction in activated natural killer cells and CD8+ T-cell subsets, as well as an expansion of dysfunctional T cells.
Article
Hematology
Linus Angenendt, Isabel Hilgefort, Jan-Henrik Mikesch, Bernhard Schlueter, Wolfgang E. Berdel, Georg Lenz, Matthias Stelljes, Christoph Schliemann
Summary: High posttransplant magnesium levels have been independently associated with a lower relapse rate, an increased risk of acute graft-versus-host disease, and higher non-relapse mortality in patients with acute myeloid leukemia.
ANNALS OF HEMATOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Tatjana Sauerer, Giuliano Filippini Velazquez, Christoph Schmid
Summary: AML is a heterogeneous disease characterized by the expansion of immature myeloid cells in the bone marrow and peripheral blood, leading to impaired hematopoiesis and life-threatening cytopenia. Allogeneic hematopoietic stem cell transplantation is a promising therapy, but post-transplant relapse remains a major challenge. Relapse after allo-HCT is caused by immune escape mechanisms, including dysregulated HLA, alterations in immune checkpoints, and immunosuppressive tumor microenvironment.
Article
Immunology
Shuang Fan, Tian-Zhong Pan, Li-Ping Dou, Yan-Min Zhao, Xiao-Hui Zhang, Lan-Ping Xu, Yu Wang, Xiao-Jun Huang, Xiao-Dong Mo
Summary: The study aimed to assess the efficacy of preemptive interferon-alpha (IFN-alpha) treatment in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a real-world setting. The results showed that preemptive IFN-alpha treatment can eliminate measurable residual disease (MRD) in AML patients and improve leukemia-free survival.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell & Tissue Engineering
Rutvij A. Khanolkar, Rehan M. Faridi, Megan Kinzel, Kareem Jamani, Mary L. Savoie, Mona Shafey, Faisal M. Khan, Jan Storek
Summary: In cytogenetically intermediate-risk AML patients undergoing HCT, the presence of FLT3 and NPM1 mutations does not appear to have prognostic value in predicting outcomes.
Article
Biophysics
Francesca Bonifazi, Chiara Pavoni, Jacopo Peccatori, Fabio Giglio, Mario Arpinati, Alessandro Busca, Paolo Bernasconi, Anna Grassi, Anna Paola Iori, Francesca Patriarca, Lucia Brunello, Carmen Di Grazia, Angelo Michele Carella, Daniela Cilloni, Alessandra Picardi, Anna Proia, Stella Santarone, Roberto Sorasio, Paola Carluccio, Patrizia Chiusolo, Alessandra Cupri, Mario Luppi, Chiara Nozzoli, Donatella Baronciani, Marco Casini, Giovanni Grillo, Maurizio Musso, Francesco Onida, Giulia Palazzo, Matteo Parma, Stefania Tringali, Adriana Vacca, Daniele Vallisa, Nicoletta Sacchi, Elena Oldani, Arianna Masciulli, Angela Gheorghiu, Corrado Girmenia, Massimo Martino, Benedetto Bruno, Alessandro Rambaldi, Fabio Ciceri
Summary: The study focused on allo-HSCT for refractory/relapsed acute leukemias, with a 2-year overall survival rate of 19% and no significant differences in outcomes according to disease and donor type. Progression-free survival at 2 years was 19%, with relapse and non-relapse mortality rates of 49% and 33%. Acute and chronic GVHD occurred in 23 and 10 patients, respectively.
BONE MARROW TRANSPLANTATION
(2022)
Meeting Abstract
Hematology
Srdan Verstovsek, Jason Gotlib, Alessandro M. Vannucchi, Alessandro Rambaldi, Andreas Reiter, William Shomali, Tracy George, Jay L. Patel, Philomena Colucci, Huiling Zhen, Natalia Oliveira, Jean-Jacques Kiladjian
Article
Biophysics
Ryszard Swoboda, Myriam Labopin, Sebastian Giebel, Thomas Schroeder, Nicolaus Kroeger, Mutlu Arat, Bipin Savani, Alexandros Spyridonidis, Rose-Marie Hamladji, Victoria Potter, Ana Berceanu, Ibrahim Yakoub-Agha, Alessandro Rambaldi, Hakan Ozdogu, Jaime Sanz, Arnon Nagler, Mohamad Mohty
Summary: This study compared two different myeloablative conditioning regimens, FluTBI12 and FB4, before allo-HCT in AML patients. The results showed no significant differences in leukemia-free survival, overall survival, relapse incidence, and non-relapse mortality between the two groups. The incidence of acute and chronic GVHD also showed no statistical differences. In conclusion, FluTBI12 and FB4 are comparable myeloablative regimens for AML patients transplanted in CR1 and CR2.
BONE MARROW TRANSPLANTATION
(2023)
Article
Oncology
Alberto Biggi, Stephane Chauvie, Federico Fallanca, Luca Guerra, Fabrizio Bergesio, Massimo Menga, Andrea Bianchi, Michele Gregianin, Agostino Chiaravalloti, Orazio Schillaci, Chiara Pavoni, Caterina Patti, Marco Picardi, Alessandra Romano, Corrado Schiavotto, Roberto Sorasio, Simonetta Viviani, Giorgio La Nasa, Livio Trentin, Alessandro Rambaldi, Andrea Gallamini
Summary: This study demonstrates the accuracy of end-of-treatment FDG-PET/CT in predicting treatment outcome in lymphoma patients, and confirms the appropriateness of the Lugano classification for evaluation.
HEMATOLOGICAL ONCOLOGY
(2023)
Article
Oncology
Nicolas Boissel, Sabina Chiaretti, Cristina Papayannidis, Josep-Maria Ribera, Renato Bassan, Andrey N. Sokolov, Naufil Alam, Alessandra Brescianini, Isabella Pezzani, Georg Kreuzbauer, Gerhard Zugmaier, Robin Foa, Alessandro Rambaldi
Summary: This retrospective study included adult patients with B-cell ALL who were treated with blinatumomab for MRD+ or R/R B-cell ALL. The results showed significant treatment responses and survival benefits in both groups of patients.
BLOOD CANCER JOURNAL
(2023)
Letter
Oncology
Tiziano Barbui, Alessandra Carobbio, Arianna Ghirardi, Alessandra Iurlo, Valerio De Stefano, Marta Anna Sobas, Elisa Rumi, Elena Maria Elli, Francesca Lunghi, Mercedes Gasior Kabat, Beatriz Cuevas, Paola Guglielmelli, Massimiliano Bonifacio, Monia Marchetti, Alberto Alvarez-Larran, Laura Fox, Marta Bellini, Rosa Daffini, Giulia Benevolo, Gonzalo Carreno-Tarragona, Andrea Patriarca, Haifa Kathrin Al-Ali, Maria Marcio Miguel Andrade-Campos, Francesca Palandri, Claire Harrison, Maria Angeles Foncillas, Santiago Osorio, Steffen Koschmieder, Elena Magro Mazo, Jean-Jacques Kiladjian, Estefania Bolanos Calderon, Florian H. Heidel, Keina Quiroz Cervantes, Martin Griesshammer, Valentin Garcia-Gutierrez, Alberto Marin Sanchez, Juan Carlos Hernandez-Boluda, Emma Lopez Abadia, Giuseppe Carli, Miguel Sagues Serrano, Rajko Kusec, Blanca Xicoy Cirici, Margarita Guenova, Begona Navas Elorza, Anna Angona, Edyta Cichocka, Anna Kulikowska de Nalecz, Daniele Cattaneo, Cristina Bucelli, Silvia Betti, Oscar Borsani, Fabrizio Cavalca, Sara Carbonell, Natalia Curto-Garcia, Lina Benajiba, Alessandro Rambaldi, Alessandro Maria Vannucchi
BLOOD CANCER JOURNAL
(2022)
Article
Hematology
Giulia Maggioni, Matteo Bersanelli, Erica Travaglino, Ana Alfonso Pierola, Annika Kasprzak, Arnan Sangerman Montserrat, Elisabetta Sauta, Claudia Sala, Tommaso Matteuzzi, Manja Meggendorfer, Matteo Gnocchi, Lin--Pierre Zhao, Cristina Astrid Tentori, Kathrin Nachtkamp, Daniele Dall'Olio, Ettore Mosca, Marta Ubezio, Alessia Campagna, Antonio Russo, Giulia Rivoli, Massimo Bernardi, Lorenza Borin, Maria Teresa Voso, Marta Riva, Esther Natalie Oliva, Matteo Zampini, Elena Riva, Elena Saba, Saverio D'Amico, Luca Lanino, Benedetta Tinterri, Francesca Re, Marilena Bicchieri, Laura Giordano, Giovanni Angelotti, Pierandrea Morandini, Anne Sophie Kubasch, Francesco Passamonti, Alessandro Rambaldi, Victor Savevski, Armando Santoro, Arjan A. van de Loosdrecht, Alice Brogi, Valeria Santini, Shahram Kordasti, Guillermo Sanz, Francesc Sole, Norbert Gattermann, Wolfgang Kern, Uwe Platzbecker, Lionel Ades, Pierre Fenaux, Torsten Haferlach, Gastone Castellani, Ulrich Germing, Maria Diez--Campelo, Matteo G. Della Porta
Summary: This study aimed to describe sex diversity in myelodysplastic syndromes and incorporate sex information into clinical decision-making. The study found differences between men and women in terms of disease genotype, phenotype, and clinical outcomes. Moreover, new prognostic models that included sex information were developed and performed better than the revised International Prognostic Scoring System.
LANCET HAEMATOLOGY
(2023)
Review
Oncology
Federico Lussana, Gianluca Cavallaro, Pantaleo De Simone, Alessandro Rambaldi
Summary: In this review, the impact of novel immune therapies on the treatment of acute lymphoblastic leukemia (ALL) in children and adults was discussed. Results from trials evaluating the incorporation of these new drugs into frontline treatments show promising clinical benefit. Clinical conditions, such as high tumor burden or extra medullary relapse, still have poor clinical outcome despite the promising results. Combination of immunotherapies with chemotherapy in frontline treatment is being evaluated to increase the rate and depth of molecular remission. The use of tyrosine kinase inhibitors and immunotherapy in Ph-positive ALL has shown unprecedented rates of remission and long-term cure. The development of potentially curative treatment modalities for older ALL patients who cannot receive intensive chemotherapy is also highlighted.
Article
Biology
Alberto Magi, Gianluca Mattei, Alessandra Mingrino, Chiara Caprioli, Chiara Ronchini, GianMaria Frige, Roberto Semeraro, Davide Bolognini, Alessandro Rambaldi, Anna Candoni, Emanuela Colombo, Luca Mazzarella, Pier Giuseppe Pelicci
Summary: DNA methylation patterns in sparse CpG regions drive chemoresistance in Acute Myeloid Leukemia patients.
COMMUNICATIONS BIOLOGY
(2023)
Correction
Biology
Alberto Magi, Gianluca Mattei, Alessandra Mingrino, Chiara Caprioli, Chiara Ronchini, Gianmaria Frige, Roberto Semeraro, Davide Bolognini, Alessandro Rambaldi, Anna Candoni, Emanuela Colombo, Luca Mazzarella, Pier Giuseppe Pelicci
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Gabriele Casirati, Andrea Cosentino, Adele Mucci, Mohammed Salah Mahmoud, Iratxe Ugarte Zabala, Jing Zeng, Scott B. Ficarro, Denise Klatt, Christian Brendel, Alessandro Rambaldi, Jerome Ritz, Jarrod A. Marto, Danilo Pellin, Daniel E. Bauer, Scott A. Armstrong, Pietro Genovese
Summary: Epitope engineering of donor haematopoietic stem/progenitor cells endows haematopoietic lineages with selective resistance to CAR T cells or monoclonal antibodies, without affecting protein function or regulation, enabling the targeting of genes that are essential for leukaemia survival and reducing the risk of tumour immune escape.
Letter
Oncology
Alessandra Carobbio, Alessandro Maria Vannucchi, Elisa Rumi, Valerio De Stefano, Alessandro Rambaldi, Giuseppe Carli, Maria Luigia Randi, Heinz Gisslinger, Francesco Passamonti, Juergen Thiele, Naseema Gangat, Ayalew Tefferi, Tiziano Barbui
BLOOD CANCER JOURNAL
(2023)
Meeting Abstract
Oncology
Hermann Einsele, Larry D. Anderson, Nina Shah, Sundar Jagannath, Jesus Berdeja, Sagar Lonial, Noopur Raje, David S. Siegel, Yi Lin, Philippe Moreau, Ibrahim Yakoub-Agha, Michel Delforge, Hartmut Goldschmidt, Katja Weisel, Michele Cavo, Donna Reece, Alessandro Rambaldi, Anna Truppel-Hartmann, Payal Patel, Liping Huang, Timothy B. Campbell, Kristen Hege, Jesus San-Miguel, Nikhil C. Munshi, Albert Oriol
ONCOLOGY RESEARCH AND TREATMENT
(2022)
Proceedings Paper
Computer Science, Interdisciplinary Applications
Yeman Brhane Hagos, Ayse U. Akarca, Alan Ramsay, Riccardo L. Rossi, Sabine Pomplun, Alessia Moioli, Andrea Gianatti, Christopher Mcnamara, Alessandro Rambaldi, Sergio A. Quezada, David Linch, Giuseppe Gritti, Teresa Marafioti, Yinyin Yuan
Summary: Multispectral immunofluorescence (M-IF) analysis is a valuable tool for investigating tissue sections and spatial interaction of cells. In this study, a deep learning-based tool called DeepMIF was developed to accurately detect and quantify cell phenotypes on M-IF images and visualize them. The results demonstrate that DeepMIF is an accurate and efficient tool for the analysis and visualization of M-IF images.
MEDICAL IMAGE COMPUTING AND COMPUTER ASSISTED INTERVENTION, MICCAI 2022, PT IV
(2022)