Review
Oncology
John Mascarenhas, Helene F. E. Gleitz, Helen T. Chifotides, Claire N. Harrison, Srdan Verstovsek, Alessandro Maria Vannucchi, Raajit K. Rampal, Jean-Jacques Kiladjian, William Vainchenker, Ronald Hoffman, Rebekka K. Schneider, Alan F. List
Summary: Myelofibrosis is a myeloproliferative disorder with significant biological and clinical heterogeneity. It can manifest as a cytopenic phenotype or a myeloproliferative phenotype, each with different prognosis and response to treatment. Patients with the cytopenic phenotype have worse outcomes and pose challenges in treatment. Recent data suggest that an innate immune deregulated state may be associated with the cytopenic phenotype, providing potential for novel treatment approaches.
Article
Hematology
Sebastiano Rontauroli, Sara Castellano, Paola Guglielmelli, Roberta Zini, Elisa Bianchi, Elena Genovese, Chiara Carretta, Sandra Parenti, Sebastian Fantini, Selene Mallia, Lara Tavernari, Stefano Sartini, Margherita Mirabile, Carmela Mannarelli, Francesca Gesullo, Annalisa Pacilli, Daniela Pietra, Elisa Rumi, Silvia Salmoiraghi, Barbara Mora, Laura Villani, Andrea Grilli, Vittorio Rosti, Giovanni Barosi, Francesco Passamonti, Alessandro Rambaldi, Luca Malcovati, Mario Cazzola, Silvio Bicciato, Enrico Tagliafico, Alessandro M. Vannucchi, Rossella Manfredini
Summary: This study demonstrates that gene expression profiles in MF patients correlate with their survival and clinical features, particularly high-risk patients showing inferior overall survival and leukemia-free survival. High-risk patients are enriched in post-PV and post-ET MF, JAK2V617F homozygous patients, and typically display high molecular risk mutations.
Review
Cell Biology
Giuseppe G. Loscocco, Giacomo Coltro, Paola Guglielmelli, Alessandro M. Vannucchi
Summary: Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are clonal disorders driven by mutations in JAK2, CALR, and MPL, leading to abnormal proliferation of mature cells. Mutation profiling, in combination with other variables, can be used for risk stratification and monitoring of residual disease and treatment response in MPN patients. Extensive characterization of the pathologic genome highlights selected mutations for clinical informativeness and potential impact on patient management.
Article
Medical Laboratory Technology
Yue Zhao, Deepti Reddi, Jenna McCracken, Natasha Iranzad, Cathrine Rehder, Jadee Neff, Endi Wang
Summary: The majority of MPNs with concomitant JAK2(V617F) and BCR-ABL1 are composite MPNs with a second hit residing on a different clone. Rare cases demonstrate a subclone harboring a double-hit in a background of a JAK2(V617F)-positive stem line clone. The probability of a double-hit with a BCR-ABL1(+) stem line clone is probably reduced by effective tyrosine kinase inhibitor treatment.
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
(2022)
Review
Hematology
Francesco Passamonti, Barbara Mora
Summary: The clinical phenotype of myelofibrosis is characterized by splenomegaly, symptomatology, blood cell alterations, and vascular complications. Diagnosis requires evaluations of blood counts, bone marrow morphology, genetic mutations, and disease history. Treatment options include anemia-oriented therapies and JAK inhibitors, with stem cell transplant being the only curative option. New paradigms for evaluating efficacy and translational studies show promise for future strategies in MF patients.
Article
Oncology
Ghaith Abu-Zeinah, Spencer Krichevsky, Tatiana Cruz, Gabriela Hoberman, Diana Jaber, Niamh Savage, Claudia Sosner, Ellen K. Ritchie, Joseph M. Scandura, Richard T. Silver
Summary: The study suggests that treatment of PV with rIFN alpha can reduce the risk of myelofibrosis and mortality, especially in high-risk patients.
Article
Hematology
Adrian Mosquera-Orgueira, Manuel Perez-Encinas, Alberto Hernandez-Sanchez, Teresa Gonzalez-Martinez, Eduardo Arellano-Rodrigo, Javier Martinez-Elicegui, Angela Villaverde-Ramiro, Jose-Maria Raya, Rosa Ayala, Francisca Ferrer-Marin, Maria-Laura Fox, Patricia Velez, Elvira Mora, Blanca Xicoy, Maria-Isabel Mata-Vazquez, Maria Garcia-Fortes, Anna Angona, Beatriz Cuevas, Maria-Alicia Senin, Angel Ramirez-Payer, Maria-Jose Ramirez, Raul Perez-Lopez, Sonia Gonzalez de Villambrosia, Clara Martinez-Valverde, Maria-Teresa Gomez-Casares, Carmen Garcia-Hernandez, Mercedes Gasior, Beatriz Bellosillo, Juan-Luis Steegmann, Alberto Alvarez-Larran, Jesus Maria Hernandez-Rivas, Juan Carlos Hernandez-Boluda
Summary: In this study, a prediction model called AIPSS-MF was developed based on 8 clinical variables at diagnosis, which accurately predicts overall survival and leukemia-free survival in patients with primary and secondary myelofibrosis.
Article
Multidisciplinary Sciences
Mattheus H. E. Wildschut, Julien Mena, Cyril Dordelmann, Marc van Oostrum, Benjamin D. Hale, Jens Settelmeier, Yasmin Festl, Veronika Lysenko, Patrick M. Schurch, Alexander Ring, Yannik Severin, Michael S. Bader, Patrick G. A. Pedrioli, Sandra Goetze, Audrey van Drogen, Stefan Balabanov, Radek C. Skoda, Massimo Lopes, Bernd Wollscheid, Alexandre P. A. Theocharides, Berend Snijder
Summary: In this study, we integrated ex vivo drug response and proteotype analyses to discover targetable vulnerabilities and associated therapeutic strategies for myelofibrosis patients. We identified three targetable vulnerabilities, including the sensitivity to BET and HDAC inhibitors driven by CALR mutations, the sensitivity to drugs targeting pro-survival signaling and DNA replication associated with an MCM complex-high proliferative signature, and the ER stress response in homozygous CALR mutations. Our findings provide a molecularly motivated roadmap for individualized treatment of myelofibrosis patients.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Kotaro Shide, Katsuto Takenaka, Akira Kitanaka, Akihiko Numata, Takuro Kameda, Takuji Yamauchi, Atsushi Inagaki, Shohei Mizuno, Akiyoshi Takami, Shinichi Ito, Masao Hagihara, Kensuke Usuki, Takaaki Maekawa, Kazutaka Sunami, Yasunori Ueda, Miyuki Tsutsui, Miki Ando, Norio Komatsu, Keiya Ozawa, Mineo Kurokawa, Shunya Arai, Kinuko Mitani, Koichi Akashi, Kazuya Shimoda
Summary: This study conducted a real-world survey to investigate the clinical characteristics and prognosis of patients with post-essential thrombocythemia myelofibrosis (PET-MF) and post-polycythemia vera myelofibrosis (PPV-MF) in the ruxolitinib era. The findings showed that PET-MF and PPV-MF patients had similar demographics, diagnosis times, and treatment approaches. The overall survival rates were also comparable between the two groups.
ANNALS OF HEMATOLOGY
(2023)
Article
Oncology
Maria Garcia-Fortes, Juan C. Hernandez-Boluda, Alberto Alvarez-Larran, Jose M. Raya, Anna Angona, Natalia Estrada, Laura Fox, Beatriz Cuevas, Maria C. Garcia-Hernandez, Maria Teresa Gomez-Casares, Francisca Ferrer-Marin, Silvana Saavedra, Francisco Cervantes, Regina Garcia-Delgado
Summary: The presence of comorbidities in myelofibrosis patients can significantly impact survival outcomes, with conditions such as hypertension, smoking, dyslipidemia, and hepatitis C virus being the most adverse factors associated with reduced overall survival.
Article
Multidisciplinary Sciences
Derek W. Brown, Weiyin Zhou, Youjin Wang, Kristine Jones, Wen Luo, Casey Dagnall, Kedest Teshome, Alyssa Klein, Tongwu Zhang, Shu-Hong Lin, Olivia W. Lee, Sairah Khan, Jacqueline B. Vo, Amy Hutchinson, Jia Liu, Jiahui Wang, Bin Zhu, Belynda Hicks, Andrew St Martin, Stephen R. Spellman, Tao Wang, H. Joachim Deeg, Vikas Gupta, Stephanie J. Lee, Neal D. Freedman, Meredith Yeager, Stephen J. Chanock, Sharon A. Savage, Wael Saber, Shahinaz M. Gadalla, Mitchell J. Machiela
Summary: The study identified 6 germline susceptibility loci and high frequencies of mosaic chromosomal alterations (mCAs) in myelofibrosis cases. The mCAs involving JAK2 were found to be strong promoters of clonal expansion in mutated clones of myelofibrosis cases.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Tamara K. Moyo, Ashwin Kishtagari, Matthew T. Villaume, Brandon McMahon, Sanjay R. Mohan, Tess Stopczynski, Sheau-Chiann Chen, Run Fan, Yuankai Huo, Hyeonsoo Moon, Yucheng Tang, Cosmin A. Bejan, Merrida Childress, Ingrid Anderson, Kyle Rawling, Rhea M. Simons, Ashley Moncrief, Rebekah Caza, Laura Dugger, Aunshka Collins, Channing Dudley, P. Brent Ferrell, Michael Byrne, Stephen A. Strickland, Gregory D. Ayers, Bennett A. Landman, Emily F. Mason, Ruben A. Mesa, Jeanne M. Palmer, Laura C. Michaelis, Michael R. Savona
Summary: This study evaluated the safety and efficacy of a combination treatment of a selective PI3KS inhibitor, umbralisib, and a JAK inhibitor, ruxolitinib, for patients with MF. The results showed that the combination treatment was well tolerated and could potentially resensitize patients to ruxolitinib.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Aaron T. Gerds
Summary: Mutations play a critical role in understanding the pathobiology of JAK/STAT activation in myeloproliferative neoplasms (MPNs), shaping the diagnostic classification, prognosis, and disease progression biology. Current research is focused on understanding the mechanisms of mutation occurrence and developing strategies to target them for disease management.
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
(2021)
Article
Hematology
Yoko Edahiro
Summary: Polycythemia vera and essential thrombocythemia are the most common subtypes of Philadelphia chromosome-negative myeloproliferative neoplasm. The main treatment strategy for these diseases is to prevent thrombotic complications, with hydroxyurea being the first-line agent. However, alternative treatment options such as JAK inhibitors and HDAC inhibitors have also been developed.
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2022)
Article
Hematology
Roni Tamari, Donal P. Mclornan, Kwang Woo Ahn, Noel Estrada-Merly, Juan Carlos Hernandez-Boluda, Sergio Giralt, Jeanne Palmer, Robert Peter Gale, Zachariah Defilipp, David I. Marks, Marjolein van der Poel, Leo F. Verdonck, Minoo Battiwalla, Miguel Angel Diaz, Vikas Gupta, Haris Ali, Mark Robert Litzow, Hillard M. Lazarus, Usama Gergis, Asad Bashey, Jane Liesveld, Shahrukh Hashmi, Jeffrey J. Pu, Amer Beitinjaneh, Christopher Bredeson, David Rizzieri, Bipin N. Savani, Muhammad Bilal Abid, Siddhartha Ganguly, Vaibhav Agrawal, Vera Ulrike Bacher, Baldeep Wirk, Tania Jain, Corey Cutler, Mahmoud Aljurf, Tamila Kindwall-Keller, Mohamed A. Kharfan-Dabaja, Gerhard C. Hildebrandt, Attaphol Pawarode, Melhem M. Solh, Jean A. Yared, Michael R. Grunwald, Sunita Nathan, Taiga Nishihori, Sachiko Seo, Bart L. Scott, Ryotaro Nakamura, Betul Oran, Tomasz Czerw, Ibrahim Yakoub-Agha, Wael Saber
Summary: A prognostic model was developed for myelofibrosis patients undergoing allogeneic hematopoietic cell transplantation. Factors such as patient age, donor compatibility, and hemoglobin levels were found to be associated with mortality risk. The proposed scoring system could accurately predict overall survival and transplant-related mortality in two large cohorts.
Article
Biochemistry & Molecular Biology
Elena Genovese, Margherita Mirabile, Sebastiano Rontauroli, Stefano Sartini, Sebastian Fantini, Lara Tavernari, Monica Maccaferri, Paola Guglielmelli, Elisa Bianchi, Sandra Parenti, Chiara Carretta, Selene Mallia, Sara Castellano, Corrado Colasante, Manjola Balliu, Niccolo Bartalucci, Raffaele Palmieri, Tiziana Ottone, Barbara Mora, Leonardo Potenza, Francesco Passamonti, Maria Teresa Voso, Mario Luppi, Alessandro Maria Vannucchi, Enrico Tagliafico, Rossella Manfredini
Summary: Myelofibrosis is a type of myeloproliferative neoplasm with poor prognosis and no response to traditional therapies. Driver mutations in JAK2 and CALR impact ROS production and oxidative DNA damage, with CALR-mutated patients showing higher ROS levels and lower antioxidant activity compared to JAK2-mutated patients. High plasma levels of total antioxidant capacity are associated with adverse clinical features and poor overall survival, particularly in patients with JAK2 mutations, suggesting a different response to oxidative stress as a potential mechanism underlying myelofibrosis progression.
Letter
Hematology
Paola Guglielmelli, Arianna Ghirardi, Alessandra Carobbio, Arianna Masciulli, Chiara Maccari, Barbara Mora, Elisa Rumi, Ana Triguero, Maria Chiara Finazzi, Helna Pettersson, Chiara Paoli, Francesco Mannelli, Daniele Vanni, Alessandro Rambaldi, Francesco Passamonti, Alberto Alvarez-Larran, Bjorn Andreasson, Alessandro M. Vannucchi, Tiziano Barbui
Article
Hematology
Carlo Visco, Luigi Marcheselli, Roberto Mina, Marianna Sassone, Anna Guidetti, Domenico Penna, Chiara Cattaneo, Valentina Bonuomo, Alessandro Busca, Andres Jose Maria Ferreri, Riccardo Bruna, Luigi Petrucci, Roberto Cairoli, Marco Salvini, Lorenza Bertu, Marco Ladetto, Sofia Pilerci, Antonello Pinto, Safaa Ramadan, Francesco Marchesi, Michele Cavo, Luca Arcaini, Elisa Coviello, Alessandra Romano, Pellegrino Musto, Massimo Massaia, Nicola Fracchiolla, Monia Marchetti, Annamaria Scattolin, Maria Chiara Tisi, Antonio Cuneo, Matteo Della Porta, Livio Trentin, Marco Turrini, Filippo Gherlinzoni, Agostino Tafuri, Sara Galimberti, Monica Bocchia, Valeria Cardinali, Daniela Cilloni, Alessandro Corso, Daniele Armiento, Luigi Rigacci, Elettra Ortu La Barbera, Carlo Gambacorti-Passerini, Giuseppe Visani, Daniele Vallisa, Adriano Venditti, Carmine Selleri, Annarita Conconi, Patrizia Tosi, Francesco Lanza, Anna Candoni, Mauro Krampera, Paolo Corradini, Francesco Passamonti, Francesco Merli
Summary: This study investigated the clinical behavior and clinical parameters of lymphoma patients with COVID-19, with the aim of identifying predictors of death. The results showed that lymphoma patients had poor outcomes when diagnosed with COVID-19, but treatment for lymphoma did not impact survival. The study also identified four easy-to-use factors associated with the risk of death.
Article
Hematology
John Mascarenhas, Francesco Passamonti, Kate Burbury, Tarec Christoffer El-Galaly, Aaron Gerds, Vikas Gupta, Brian Higgins, Kathrin Wonde, Candice Jamois, Bruno Kovic, Ling-Yuh Huw, Sudhakar Katakam, Margherita Maffioli, Ruben Mesa, Jeanne Palmer, Marta Bellini, David M. Ross, Alessandro M. Vannucchi, Abdulraheem Yacoub
Summary: Idasanutlin, an MDM2 antagonist, has shown clinical activity and rapid reduction in JAK2 mutation burden in patients with polycythemia vera (PV), but long-term tolerability is limited due to high gastrointestinal toxicity.
Article
Hematology
Margherita Maffioli, Barbara Mora, Somedeb Ball, Alessandra Iurlo, Elena Maria Elli, Maria Chiara Finazzi, Nicola Polverelli, Elisa Rumi, Marianna Caramella, Maria Cristina Carraro, Mariella D'Adda, Alfredo Molteni, Cinzia Sissa, Francesca Lunghi, Alessandro Vismara, Marta Ubezio, Anna Guidetti, Sabrina Caberlon, Michela Anghilieri, Rami Komrokji, Daniele Cattaneo, Matteo Giovanni Della Porta, Toni Giorgino, Lorenza Bertu, Marco Brociner, Andrew Kuykendall, Francesco Passamonti
Summary: Ruxolitinib is commonly used in the treatment of myelofibrosis, but many patients lose response over time. This study identified predictors of survival and developed a prognostic model to identify patients who may benefit from a treatment switch.
Article
Hematology
Claire N. Harrison, Nicolaas Schaap, Alessandro M. Vannucchi, Jean-Jacques Kiladjian, Francesco Passamonti, Sonja Zweegman, Moshe Talpaz, Srdan Verstovsek, Shelonitda Rose, Jun Zhang, Oumar Sy, Ruben A. Mesa
Summary: This study evaluated the efficacy and safety of Fedratinib in patients with low baseline platelet counts. The results indicated that Fedratinib 400 mg/day is safe and effective for patients with low platelet counts, and no initial dose adjustment is required.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Review
Oncology
Naveen Pemmaraju, Srdan Verstovsek, Ruben Mesa, Vikas Gupta, Jacqueline S. Garcia, Joseph M. Scandura, Stephen T. Oh, Francesco Passamonti, Konstanze Dohner, Adam J. Mead
Summary: This article discusses the definition of disease modification in myelofibrosis and the recent clinical trials of developing therapeutic drugs, emphasizing the need for surrogate measures of survival in early-stage trials.
Review
Oncology
Francesco Passamonti, Emanuele Nicastri, Alice Di Rocco, Attilio Guarini, Adalberto Ibatici, Stefano Luminari, Malgorzata Mikulska, Carlo Visco
Summary: This review provides the latest data on patients with lymphoma and COVID-19, and discusses practical guidance from diagnosis to follow-up. Lymphoma patients are at a higher risk of severe COVID-19 and may not be fully protected by vaccination. Passive immunization with monoclonal antibodies and antiviral drugs have shown effectiveness in managing lymphoma patients with COVID-19.
HEMATOLOGICAL ONCOLOGY
(2023)
Review
Hematology
Francesco Passamonti, Barbara Mora
Summary: The clinical phenotype of myelofibrosis is characterized by splenomegaly, symptomatology, blood cell alterations, and vascular complications. Diagnosis requires evaluations of blood counts, bone marrow morphology, genetic mutations, and disease history. Treatment options include anemia-oriented therapies and JAK inhibitors, with stem cell transplant being the only curative option. New paradigms for evaluating efficacy and translational studies show promise for future strategies in MF patients.
Article
Oncology
John Mascarenhas, Marina Kremyanskaya, Andrea Patriarca, Francesca Palandri, Timothy Devos, Francesco Passamonti, Raajit K. Rampal, Adam J. Mead, Gabriella Hobbs, Joseph M. Scandura, Moshe Talpaz, Nikki Granacher, Tim C. P. Somervaille, Ronald Hoffman, Marielle J. Wondergem, Mohamed E. Salama, Gozde Colak, Jike Cui, Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Srdan Verstovsek, Natalia Curto-Garcia, Claire Harrison, Vikas Gupta
Summary: In patients with myelofibrosis who are naive to JAKi treatment, the rational combination of the BET inhibitor pelabresib and ruxolitinib showed good tolerability and durable improvements in spleen and symptom burden.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Editorial Material
Hematology
Michele Merli, Francesco Passamonti, Luca Arcaini
Summary: Recent clinical studies have shown that patients with Hepatitis C virus-associated indolent lymphoproliferative disorders (LPD) can achieve lymphoma responses when treated solely with direct-acting antivirals (DAAs). However, the molecular mechanisms underlying LPD responses to DAAs are not well understood. In this paper, the authors provide new molecular insights, reporting intraclonal diversification and persistence of B-cell clones in most cases, even after viral eradication and positive clinical outcomes. These findings suggest that achieving a molecular response may not be necessary for a 'functional cure' in these patients. Further immunogenetic and mutational studies are needed to better understand this biological puzzle and refine treatment strategies.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Editorial Material
Hematology
Francesco Passamonti, Alessandra Bandera
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
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)
Article
Oncology
Nicola Stefano Fracchiolla, Mariarita Sciume, Cristina Papayannidis, Antonella Vitale, Sabina Chiaretti, Mario Annunziata, Fabio Giglio, Prassede Salutari, Fabio Forghieri, Davide Lazzarotto, Monia Lunghi, Annalisa Imovilli, Barbara Scappini, Massimiliano Bonifacio, Michelina Dargenio, Carmela Gurrieri, Elisabetta Todisco, Marzia Defina, Maria Ilaria Del Principe, Patrizia Zappasodi, Marco Cerrano, Lidia Santoro, Elena Tagliaferri, Enrico Barozzi, Pasquale De Roberto, Marta Canzi, Elisa Buzzatti, Chiara Sartor, Francesco Passamonti, Robin Foa, Antonio Curti, Thomas Wirth
Summary: This retrospective study evaluated the efficacy and safety of blinatumomab and inotuzumab ozogamicin in the treatment of relapsed B-lymphoblastic leukemia. The study demonstrated the feasibility and effectiveness of sequential immunotherapy using these two drugs in terms of minimal residual disease, overall survival, and disease-free survival.
Article
Oncology
Francesco Passamonti, Youbei Lou, Manoj Chevli, Pranav Abraham
Summary: This observational study evaluated the outcomes of US myelofibrosis patients who received ruxolitinib treatment, and found that subsequent treatment with fedratinib led to improved survival compared to non-fedratinib treatment.
