Article
Oncology
Paola Guglielmelli, Giuseppe G. Loscocco, Carmela Mannarelli, Elena Rossi, Francesco Mannelli, Francesco Ramundo, Giacomo Coltro, Silvia Betti, Chiara Maccari, Sara Ceglie, Patrizia Chiusolo, Chiara Paoli, Tiziano Barbui, Ayalew Tefferi, Valerio De Stefano, Alessandro M. Vannucchi
Summary: The study analyzed the impact of JAK2V617F VAF on thrombosis in PV patients, finding that VAF > 50% is an independent strong predictor of future VT, but not associated with AT. The results suggest that AT and VT may require distinct management strategies.
BLOOD CANCER JOURNAL
(2021)
Article
Multidisciplinary Sciences
Yusuke Kimishima, Tomofumi Misaka, Tetsuro Yokokawa, Kento Wada, Koki Ueda, Koichi Sugimoto, Keiji Minakawa, Kazuhiko Nakazato, Takafumi Ishida, Motohiko Oshima, Shuhei Koide, Kotaro Shide, Kazuya Shimoda, Atsushi Iwama, Kazuhiko Ikeda, Yasuchika Takeishi
Summary: The study demonstrates that clonal hematopoiesis with JAK2V617F exacerbates PH by promoting the accumulation of neutrophils in pulmonary arterial regions, ultimately leading to pulmonary arterial remodeling and increased disease severity.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Amanda Fernandes de Oliveira Costa, Leticia Olops Marani, Thiago Mantello Bianco, Adriana Queiroz Arantes, Izabela Aparecida Lopes, Diego Antonio Pereira-Martins, Leonardo Carvalho Palma, Priscila Santos Scheucher, Josiane Lilian dos Santos Schiavinato, Larissa Sarri Binelli, Cleide Araujo Silva, Susumu S. Kobayashi, Joao Agostinho Machado-Neto, Eduardo Magalhaes Rego, Robert Samuel Welner, Lorena Lobo de Figueiredo-Pontes
Summary: NK cells play a role in eliminating tumor cells through direct cytolytic activity and promoting antitumor immune response. This study suggests that NK cells in myeloproliferative neoplasms (MPN) have an immature phenotype and deficient cytotoxicity, which may lead to impaired tumor surveillance.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Yan Wang, Fei Ran, Jin Lin, Jing Zhang, Dan Ma
Summary: Simultaneous mutations in JAK2, calreticulin, and MPL genes are often overlooked, leading to misdiagnosis of Philadelphia-negative myeloproliferative neoplasms. A retrospective analysis found that the majority of double mutations in MPN patients were JAKV617F-CALR, followed by JAKV617F-MPL and CALR-MPL mutations. These patients had distinct clinical characteristics and poorer treatment response. Customized treatment may be the best option for MPN patients with co-mutations.
TECHNOLOGY IN CANCER RESEARCH & TREATMENT
(2023)
Article
Oncology
Daisuke Shinoda, Yaeko Nakajima-Takagi, Motohiko Oshima, Shuhei Koide, Kazumasa Aoyama, Atsunori Saraya, Hironori Harada, Bahityar Rahmutulla, Atsushi Kaneda, Kiyoshi Yamaguchi, Yoichi Furukawa, Haruhiko Koseki, Kazuya Shimoda, Tomoaki Tanaka, Goro Sashida, Atsushi Iwama
Summary: The insufficiency of PRC1.1, a component of polycomb repressive complex 1, promotes the development of myelofibrosis and acts as a tumor suppressor in this process. This impact is distinct from the effect of PRC2 insufficiency on the pathogenesis of myelofibrosis.
Article
Hematology
Alison R. Moliterno, Hannah Kaizer, Brandi N. Reeves
Summary: Polycythemia vera (PV) is a hematopoietic stem cell neoplasm characterized by overproduction of red blood cells, platelets, and neutrophils due to activating somatic mutations in the JAK2 gene. This disease is associated with significant burden of symptoms, high rates of vascular events, and progression to myelofibrosis phase or acute leukemia. The JAK2(V617F) variant allele frequency (VAF) plays a crucial role in the pathogenesis, diagnosis, prognosis, and treatment of PV.
Article
Hematology
Snjezana Janjetovic, Lennart Beckmann, Katharina Holstein, Christina Rolling, Benjamin Thiele, Philippe Schafhausen, Gerhard Schoen, Carsten Bokemeyer, Florian Langer, Minna Voigtlaender
Summary: The study identified a significant association between JAK2V617F-positive MPN and definite APS, with patients with APS potentially experiencing earlier onset of thrombotic events, necessitating more aggressive antithrombotic treatment strategies.
THROMBOSIS RESEARCH
(2021)
Article
Hematology
Graciela Rabadan Moraes, Florence Pasquier, Christophe Marzac, Eric Deconinck, Carlotta Caterina Damanti, Gwendoline Leroy, Mira El-Khoury, Wassim El Nemer, Jean-Jacques Kiladjian, Hana Raslova, Albert Najman, William Vainchenker, Caroline Marty, Christine Bellanne-Chantelot, Isabelle Plo
Summary: This study identified an EPOR variant in a large family with JAK2-positive MPN, indicating the importance of inherited-risk alleles affecting the JAK2/STAT pathway in MPN. The findings suggest potential implications for risk assessment and treatment of MPN.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anders L. Sorensen, Hans C. Hasselbalch, Mads Emil Bjorn, Claus H. Nielsen, Sabrina Cordua, Vibe Skov, Lasse Kjaer, Henrik E. Poulsen, Christina Ellervik
Summary: The study suggests a potential association between somatic mutations in MPNs and oxidative stress, with higher levels of oxidative stress markers in mutation-positive individuals. Impaired mitochondrial antioxidative defense may contribute to the development of mutations associated with MPNs.
Article
Biotechnology & Applied Microbiology
Jie Zhou, Hao Wu, Cheng Guo, Bing Li, Li-Li Zhou, Ai-Bin Liang, Jian-Fei Fu
Summary: The study identified the expression and regulation patterns of lncRNAs in JAK2V617F-positive cMPNs, along with potential carcinogenic factors and signaling pathways related to dysregulated lncRNAs and important genes. Further investigation is warranted to explore the role of these factors in the pathogenesis of cMPNs.
Article
Cell Biology
Kengo Takeda, Kenji Tago, Megumi Funakoshi-Tago
Summary: The point mutation (V617F) in the JAK2 gene promotes the expression of DDX5, which contributes to the development of MPN through the activation of STAT5. Inhibition of DDX5 suppresses mTOR activation, cell proliferation, and tumor growth in a mouse model of MPN.
CELLULAR SIGNALLING
(2023)
Article
Hematology
Samah Alimam, William Villiers, Richard Dillon, Michael Simpson, Manohursingh Runglall, Alexander Smith, Prodromos Chatzikyriakou, Paul Lavender, Anju Kanda, Ken Mills, Beatriz Bellosillo Paricio, James Kaufman-Cook, Sophie Ord, Shahram Kordasti, Deepti Radia, Claire Woodley, Yvonne Francis, Ghulam Mufti, Donal P. McLornan, Claire N. Harrison
Summary: The study identified similar patterns of gene expression and DNA methylation in patients with essential thrombocythemia (ET) with known driver mutations and those with triple-negative disease, suggesting that the ET phenotype may be primarily driven by transcriptional misregulation and may propagate downstream via MAPK, tumor necrosis factor, and NF kappa B pathways. These findings highlight potential novel mechanisms of disease initiation that require further evaluation.
Article
Oncology
Antonio Bruno Alves-Silva, Bruna Alves Fenerich, Natasha Peixoto Fonseca, Jaqueline Cristina Fernandes, Juan Luiz Coelho-Silva, Diego Antonio Pereira-Martins, Thiago Mantello Bianco, Priscila Santos Scheucher, Eduardo Magalhaes Rego, Fernando Chahud, Joao Agostinho Machado-Neto, Lorena Lobo Figueiredo-Pontes, Fabiola Traina
Summary: This study investigated the effects of phenformin on Jak2(V617F)-knockin MPN mice. The results showed that phenformin increased the percentages of LSK, MP, and MPP populations in the bone marrow, but did not reduce the disease burden. Further studies are needed to understand the effects of phenformin on early hematopoietic progenitors.
INVESTIGATIONAL NEW DRUGS
(2022)
Article
Multidisciplinary Sciences
Ron Baik, Stacia K. Wyman, Shaheen Kabir, Jacob E. Corn
Summary: This study demonstrates the use of CRISPR-Cas9 engineering to create and reverse the JAK2 V617F mutation in human cell lines and hematopoietic stem cells. The mutation was found to provide a competitive growth advantage and promote terminal differentiation of erythroid progenitors, highlighting the potential role of endogenously acquired JAK2 V617F mutations in myeloproliferative neoplasms.
Review
Microbiology
Christina Schjellerup Eickhardt-Dalboge, Anna Cacilia Ingham, Henrik V. Nielsen, Kurt Fuursted, Christen Rune Stensvold, Lee O'Brien Andersen, Morten Kranker Larsen, Lasse Kjaer, Sarah Friis Christensen, Trine Alma Knudsen, Vibe Skov, Christina Ellervik, Lars Ronn Olsen, Hans Carl Hasselbalch, Jens Jorgen Elmer Christensen, Xiaohui Chen Nielsen
Summary: This study investigates the gut microbiota in patients with essential thrombocythemia (ET) and found that they have higher richness and different bacterial composition compared to healthy controls. The relative abundance of certain bacteria within the Firmicutes phylum is lower in ET patients, including an important immunoregulative bacterium Faecalibacterium. These findings suggest a potential role of gut microbiota in immune dysregulation of ET patients.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biophysics
Juan-Carlos Hernandez-Boluda, Arturo Pereira, Nienke Zinger, Luuk Gras, Rodrigo Martino, Shankara Paneesha, Juergen Finke, Anabelle Chinea, Alessandro Rambaldi, Marie Robin, Riccardo Saccardi, Annalisa Natale, John A. Snowden, Panagiotis Tsirigotis, Carlos Vallejo, Gerald Wulf, Blanca Xicoy, Domenico Russo, Johan Maertens, Etienne Daguindau, Stig Lenhoff, Patrick Hayden, Tomasz Czerw, Donal P. McLornan, Ibrahim Yakoub-Agha
Summary: Allogeneic hematopoietic cell transplantation shows significant curative potential in patients with FGFR1-rearranged myeloid/lymphoid neoplasm. This study reports on the largest series of FGFR1-rearranged MLN patients undergoing allo-HCT, demonstrating promising overall results in the treatment of this aggressive disease.
BONE MARROW TRANSPLANTATION
(2022)
Article
Oncology
Luca Ceriani, Lisa Milan, Luciano Cascione, Giuseppe Gritti, Federico Dalmasso, Fabiana Esposito, Maria Cristina Pirosa, Saemi Schaer, Andrea Bruno, Stephan Dirnhofer, Luca Giovanella, Stefanie Hayoz, Christoph Mamot, Alessandro Rambaldi, Stephane Chauvie, Emanuele Zucca
Summary: Functional parameters from positron emission tomography (PET) show promise as biomarkers in different lymphoma subtypes, with radiomics features extracted using PyRadiomics Python package. A prognostic radiomics score (RS) based on PET-derived data was able to significantly predict progression-free survival (PFS), cause-specific survival (CSS), and overall survival (OS) in both testing and validation sets of DLBCL patients, showing better predictive accuracy compared to clinical international indices.
HEMATOLOGICAL ONCOLOGY
(2022)
Article
Hematology
Marina Y. Konopleva, Christoph Roellig, Jamie Cavenagh, Dries Deeren, Larisa Girshova, Juergen Krauter, Giovanni Martinelli, Pau Montesinos, Jonas A. Schaefer, Oliver Ottmann, Mario Petrini, Arnaud Pigneux, Alessandro Rambaldi, Christian Recher, Rebeca Rodriguez-Veiga, David Taussig, Norbert Vey, Sung-Soo Yoon, Marion Ott, Susanne Muehlbauer, Benjamin M. Beckermann, Olivier Catalani, Magali Genevray, Kirsten Mundt, Candice Jamois, Pierre Fenaux, Andrew H. Wei
Summary: A study evaluating the efficacy and safety of the MDM2 antagonist idasanutlin plus cytarabine in patients with relapsed/refractory acute myeloid leukemia found that this combination did not improve overall survival or complete remission rates, despite an increased overall response rate.
Article
Pathology
Irene Della Starza, Lucia A. De Novi, Alessandra Santoro, Domenico Salemi, Orietta Spinelli, Manuela Tosi, Roberta Soscia, Francesca Paoloni, Luca V. V. Cappelli, Marzia Cavalli, Valerio Apicella, Vittorio Bellomarino, Eleonora Di Lello, Antonella Vitale, Marco Vignetti, Francesco Fabbiano, Alessandro Rambaldi, Renato Bassan, Anna Guarini, Sabina Chiaretti, Robin Foa
Summary: This study compared RQ-PCR and ddPCR analysis of 116 samples from 44 acute lymphoblastic leukemia patients, confirming the advantages of ddPCR in disease level quantification and improving patient risk stratification.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2022)
Meeting Abstract
Hematology
Chiara Paoli, Paola Guglielmelli, Francesco Mannelli, Miriam Borella, Vittorio Rosti, Elisa Rumi, Maria Chiara Finazzi, Oscar Borsani, Carmela Mannarelli, Maria Esposito, Mario Xhani, Lisa Pieri, Tiziano Barbui, Alessandro Rambaldi, Alessandro Vannucchi
Meeting Abstract
Hematology
Elisabetta Sauta, Marie Robin, Matteo Bersanelli, Erica Travaglino, Manja Meggendorfer, Lin-Pierre Zhao, Juan Carlos Caballero Berrocal, Giulia Maggioni, Cristina Astrid Tentori, Massimo Bernardi, Carmen Di Grazia, Luca Vago, Giulia Rivoli, Lorenza Borin, Saverio D'Amico, Marta Ubezio, Alessia Campagna, Antonio Russo, Daniele Mannina, Luca Lanino, Patrizia Chiusolo, Luisa Giaccone, Maria Teresa Voso, Marta Riva, Esther Natalie Oliva, Matteo Zampini, Elena Riva, Olivier Nibourel, Claudia Sala, Marilena Bicchieri, Niccolo Bolli, Alessandro Rambaldi, Francesco Passamonti, Victor Savevski, Armando Santoro, Ulrich Germing, Shahram Kordasti, Valeria Santini, Maria Diez-Campelo, Guillermo Sanz, Francesc Sole, Wolfgang Kern, Uwe Platzbecker, Lionel Ades, Pierre Fenaux, Torsten Haferlach, Castellani Gastone, Matteo G. Della Porta
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)
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)