Article
Hematology
Justin Anthony Chen, Yanli Hou, Krishna M. Roskin, Daniel A. Arber, Charles D. Bangs, Linda B. Baughn, Athena M. Cherry, Mark D. Ewalt, Andrew Z. Fire, Laure Fresard, Hutton M. Kearney, Stephen B. Montgomery, Robert S. Ohgami, Kathryn E. Pearce, Beth A. Pitel, Jason D. Merker, Jason Gotlib
Summary: The resistance mechanisms to ruxolitinib in a patient with JAK2-driven hematologic malignancies may involve IKZF1 deletion and an activated B-cell receptor-like signaling phenotype.
Article
Oncology
Helna Pettersson, Jenni Adamsson, Peter Johansson, Staffan Nilsson, Lars Palmqvist, Bjoern Andreasson, Julia Asp
Summary: This study aimed to analyze genetic variants with prognostic value in a population-based MPN cohort. The study found that mutations in the SRSF2 and U2AF1 genes were significantly correlated with impaired overall survival, but not with an increased risk of vascular events. Several genetic variants with a close to 50% allele frequency were also identified, but they did not show an earlier onset of MPN.
FRONTIERS IN ONCOLOGY
(2023)
Article
Genetics & Heredity
Jin Zhang, Kefeng Shen, Min Xiao, Jinjin Huang, Jin Wang, Yaqin Wang, Zhenya Hong
Summary: Novel pathogenic mutations were discovered by targeted NGS in 4 patients diagnosed with JAK2 unmutated PV or TN MPN. NGS is required to detect non-canonical driver variants and avoid misdiagnosis of TN MPN.
FRONTIERS IN GENETICS
(2023)
Review
Oncology
Jerry L. Spivak, Alison R. Moliterno
Summary: The myeloproliferative neoplasms, including polycythemia vera, essential thrombocytosis, and primary myelofibrosis, share driver mutations that result in increased production of blood cells. In addition, these disorders also share an abnormality in MPL posttranslational processing which has not been well recognized.
FRONTIERS IN ONCOLOGY
(2021)
Article
Hematology
Liping Li, Jung-Hyun Kim, Wenyan Lu, Donna M. Williams, Joseph Kim, Leslie Cope, Raajit K. Rampal, Richard P. Koche, Lingling Xian, Li Z. Luo, Marija Vasiljevic, Daniel R. Matson, Zhizhuang Joe Zhao, Ophelia Rogers, Matthew C. Stubbs, Karen Reddy, Antonio-Rodriguez Romero, Bethan Psaila, Jerry L. Spivak, Alison R. Moliterno, Linda M. S. Resar
Summary: The study reveals HMGA1 as a novel driver of myeloproliferative neoplasms transformation, depletion of which can prevent the progression of blood cell proliferative diseases and is associated with the GATA2 gene. These findings highlight HMGA1 as a potential new therapeutic target for treating or preventing related disease progression.
Article
Oncology
Daniel Nathan, Jonathan Feld, Siraj M. El Jamal, John Mascarenhas, Douglas Tremblay
Summary: MDS/MPN-RS-T is a rare hematologic malignancy belonging to the category of myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes. It is characterized by clinical features such as anemia and thrombocytosis, but the presence of the spliceosome mutation SF3B1 leads to notable exceptions. The overall and leukemia free survival of MDS/MPN-RS-T is shorter compared to essential thrombocythemia (ET). Thrombotic risk in MDS/MPN-RS-T is associated with the presence of the mutated spliceosome gene SF3B1.
Article
Hematology
Peter Mueller, Conny K. Baldauf, Tobias R. Haage, Ana M. Waldleben, Fabian Richter, Klaus Pfizenmaier, Thomas Fischer
Summary: This study investigated the therapeutic effects of aTNFR1 and aTNFR2 antibody treatment in MPN-like disease induced by JAK2-V617F, showing that TNFR1 and TNFR2 play distinct roles in the biology of the disease. These findings may have relevance in future therapeutic settings.
Article
Oncology
Kaihong Xu, Qunfang Ge, Yanli Zhang, Guifang Ouyang, Xiao Yan
Summary: This study investigated the expression properties, structural features, and function of CALR E381A in patients with myeloproliferative neoplasms (MPN). The results showed that CALR E381A had a higher frequency in East Asian populations than as a single nucleotide polymorphism (SNP). It coexisted with other genetic variants, but did not change the physical properties of the calreticulin protein or affect cell growth.
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
(2023)
Article
Oncology
Kaihong Xu, Qunfang Ge, Yanli Zhang, Guifang Ouyang, Xiao Yan
Summary: This study investigated the expression properties, structural features, and function of CALR E381A in MPN patients. The CALR variants p.L367fs*46, p.K385fs*47, and p.E381A were identified as the predominant types. CALR E381A coexisted with other genetic variants, with JAK2 V617F being more common. Bioinformatics analysis showed that CALR E381A did not change the physicochemical properties of the protein but affected the electrical charge and steric hindrance of amino acids. Functional analysis indicated that CALR E381A does not alter cell growth. CALR E381A may be a risk SNP suggesting an inherited predisposition for MPN disease in East Asian populations.
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
(2023)
Review
Oncology
Garima Pandey, Andrew T. Kuykendall, Gary W. Reuther
Summary: Studies suggest that the ineffectiveness of JAK2 inhibitors in the treatment of myeloproliferative neoplasms may be due to persistent activation of JAK2-dependent signaling through various cell intrinsic and extrinsic mechanisms. Targeting MEK/ERK in combination with JAK2 inhibition has the potential to improve the efficacy of JAK2 inhibitors.
BLOOD CANCER JOURNAL
(2022)
Article
Hematology
Trine Alma Knudsen, Vibe Skov, Kristen Stevenson, Lillian Werner, William Duke, Charles Laurore, Christopher J. Gibson, Anwesha Nag, Aaron R. Thorner, Bruce Wollison, Dennis Lund Hansen, Christina Ellervik, Daniel El Fassi, Karin de Stricker, Lukas Frans Ocias, Mette Brabrand, Ole Weis Bjerrum, Ulrik Malthe Overgaard, Mikael Frederiksen, Thomas Kielsgaard Kristensen, Torben A. Kruse, Mads Thomassen, Torben Mourits-Andersen, Marianne Tang Severinsen, Jesper Stentoft, Joern Starklint, Donna S. Neuberg, Lasse Kjaer, Thomas Stauffer Larsen, Hans Carl Hasselbalch, R. Coleman Lindsley, Ann Mullally
Summary: This study found that different types of mutations have different impacts on molecular response to interferon-alpha treatment in patients with myeloproliferative neoplasms (MPNs). The study also discovered treatment-emergent mutations and their associations with prior stroke.
Article
Biochemistry & Molecular Biology
Maaike G. J. M. van Bergen, Rinske van Oorschot, Saskia M. Bergevoet, Aniek O. de Graaf, Evelyn L. R. T. M. Tonnissen, Ellen Stevens-Linders, Kornelia Neveling, Pascal W. T. C. Jansen, Marijke P. A. Baltissen, Michiel Vermeulen, Amit Mandoli, Joost H. A. Martens, Frank Preijers, Joop H. Jansen, Bert A. van der Reijden
Summary: The genomic locus 8 kb downstream of the GFI1B transcription factor is associated with clonal hematopoiesis and myeloproliferative neoplasms, with a polymorphism rs621940-G in particular. However, studies show that rs621940-G does not affect GFI1B expression, autorepression, or growth of immature myeloid cells.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Hematology
Yoko Edahiro, Tomoki Ito, Akihiko Gotoh, Mika Nakamae, Fumihiko Kimura, Michiaki Koike, Keita Kirito, Hideho Wada, Kensuke Usuki, Takayuki Tanaka, Takehiko Mori, Satoshi Wakita, Toshiki Saito, Akiko Kada, Akiko M. Saito, Kazuya Shimoda, Yuka Sugimoto, Toshiro Kurokawa, Akihiro Tomita, Yoshinori Hashimoto, Koichi Akashi, Itaru Matsumura, Katsuto Takenaka, Norio Komatsu
Summary: This study retrospectively analyzed the clinical characteristics of 596 Japanese patients with PV and found that the positive rates of JAK2 V617F and JAK2 exon 12 mutations were 94.3% and 2.1% respectively. The major causes of death were secondary malignancies, acute leukemia, non-leukemic progressive disease, and thrombotic and hemorrhagic complications. Thrombotic and hemorrhagic events occurred in 4.0% and 3.5% of patients during the clinical course. The international PV prognostic score was applicable to Japanese patients with PV.
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2022)
Editorial Material
Hematology
Andrew Dunbar, Ross L. Levine
Summary: This study reveals how HSC subpopulations contribute to MPN pathogenesis and are perturbed under pegIFN therapy.
Article
Cell & Tissue Engineering
Sharon Muggeo, Laura Crisafulli, Paolo Uva, Elena Fontana, Marta Ubezio, Emanuela Morenghi, Federico Simone Colombo, Rosita Rigoni, Clelia Peano, Paolo Vezzoni, Matteo Giovanni Della Porta, Anna Villa, Francesca Ficara
Summary: PBX1 plays a crucial role in regulating the balance between self-renewal and differentiation in hematopoietic stem cells, as well as maintaining proto-oncogenic transcriptional pathways. Studies have shown that lack of PBX1 can prevent the development of MPN caused by the JAK2V617F mutation, suggesting that modulation of the PBX1-driven transcriptional program could be a novel therapeutic approach.
Letter
Oncology
Giuseppe Auteri, Daniela Bartoletti, Christian Di Pietro, Emanuele Sutto, Camilla Mazzoni, Andrea Davide Romagnoli, Nicola Vianelli, Tiziana Lazzarotto, Michele Cavo, Francesca Palandri
Article
Oncology
Paola Ulivi, Milena Urbini, Elisabetta Petracci, Matteo Canale, Alessandra Dubini, Daniela Bartolini, Daniele Calistri, Paola Cravero, Eugenio Fonzi, Giovanni Martinelli, Ilaria Priano, Kalliopi Andrikou, Giuseppe Bronte, Lucio Crino, Angelo Delmonte
Summary: Molecular characterization of advanced non-small-cell lung cancer (NSCLC) is essential for treatment decision making, and next-generation sequencing (NGS) is the best strategy in this context. In this study, we analyzed a series of young NSCLC patients using a wide NGS gene panel assay. The most frequently mutated genes were TP53, KRAS, STK11, etc. We found a significant association between STK11 and KRAS mutations and high tumor mutational burden (TMB), while EGFR and EML4-ALK alterations were more common in tumors with low TMB. The results obtained from this approach showed perfect concordance with those obtained from a single or few genes approach.
Article
Hematology
Giuseppe Alberto Palumbo, Massimo Breccia, Claudia Barate, Massimiliano Bonifacio, Elena Maria Elli, Alessandra Iurlo, Novella Pugliese, Elena Rossi, Paola Guglielmelli, Francesca Palandri
Summary: Objectives Polycythemia vera (PV) is a clonal hematopoietic stem cell disorder characterized by overproduction of red blood cells. Treatment patterns for PV patients in Italy vary greatly across different aspects. This survey highlights the need for more precise clinical guidance for routine care of PV patients.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Andrea Ghelli Luserna di Rora, Mouna Jandoubi, Giovanni Martinelli, Giorgia Simonetti
Summary: Uncontrolled proliferative signals and cell cycle dysregulation are important drivers of leukemia, and new compounds targeting cell cycle proteins and oncogenic mechanisms show promising therapeutic potential. The development of kinase inhibitors, microtubule-depolymerizing agents, P53-restoring agents, G-quadruplex-stabilizing molecules, and inhibitors of CDK2, CHK1, PI3K delta, STAT5, BRD4, and BRPF1 have shown effectiveness in inhibiting leukemia growth. Further investigation is needed to evaluate their toxicity, bio-availability, and efficacy in clinical settings.
Article
Nutrition & Dietetics
Sara Salucci, Alberto Bavelloni, Anna Bartoletti Stella, Francesco Fabbri, Ivan Vannini, Manuela Piazzi, Karyna Volkava, Katia Scotlandi, Giovanni Martinelli, Irene Faenza, William Blalock
Summary: Approximately 7% of childhood cancers and 1% of adult cancers are soft tissue sarcomas, with rhabdomyosarcoma being the most common subtype. Despite current therapeutic protocols, survival rates for RMS have not improved significantly in the past decade. Curcumin, derived from the Curcuma longa plant, has low toxicity and has shown anti-tumorigenic effects in vitro. This study evaluated curcumin's activity in RMS cell lines and identified the major pathways affected by curcumin's anti-tumorigenic effects. Curcumin treatment resulted in cell cycle arrest, inhibited migration and colony formation, and induced apoptosis. Proteome profiler analysis revealed that curcumin primarily influenced signaling through AKT-mTOR, STAT, AMPK, and p53 pathways in a subtype-specific manner. Combinational therapeutic targeting of these pathways may be the best option for RMS treatment.
Review
Hematology
Nicola Polverelli, Juan Carlos Hernandez-Boluda, Tomasz Czerw, Tiziano Barbui, Mariella D'Adda, Hans Joachim Deeg, Markus Ditschkowski, Claire Harrison, Nicolaus Martin Kroger, Ruben Mesa, Francesco Passamonti, Francesca Palandri, Naveen Pemmaraju, Uday Popat, Damiano Rondelli, Alessandro Maria Vannucchi, Srdan Verstovsek, Marie Robin, Antonio Colecchia, Luigi Grazioli, Enrico Damiani, Domenico Russo, Jessica Brady, David Patch, Slawomir Blamek, Gandhi Laurent Damaj, Patrick Hayden, Donal P. McLornan, Ibrahim Yakoub-Agha
Summary: Splenomegaly is a common complication in myelofibrosis patients and can negatively impact outcomes of allogeneic hematopoietic cell transplantation (HCT). This Position Paper provides a shared position statement on the management of splenomegaly before HCT. The assessment, prevalence, and clinical significance of splenomegaly are discussed, along with the need for therapeutic intervention. Specific scenarios, such as splanchnic vein thrombosis and COVID-19, are also addressed.
LANCET HAEMATOLOGY
(2023)
Article
Oncology
Francesca Palandri, Massimo Breccia, Camilla Mazzoni, Giuseppe Auteri, Elena Maria Elli, Malgorzata M. M. Trawinska, Nicola Polverelli, Mario Tiribelli, Giulia Benevolo, Alessandra Iurlo, Alessia Tieghi, Florian H. H. Heidel, Giovanni Caocci, Eloise Beggiato, Gianni Binotto, Francesco Cavazzini, Maurizio Miglino, Costanza Bosi, Monica Crugnola, Monica Bocchia, Bruno Martino, Novella Pugliese, Mattia Biondo, Marta Venturi, Luigi Scaffidi, Alessandro Isidori, Daniele Cattaneo, Mauro Krampera, Fabrizio Pane, Daniela Cilloni, Gianpietro Semenzato, Roberto M. M. Lemoli, Antonio Cuneo, Elisabetta Abruzzese, Daniela Bartoletti, Simona Paglia, Nicola Vianelli, Michele Cavo, Massimiliano Bonifacio, Giuseppe A. A. Palumbo
Summary: This study explored the prognostic factors of cytopenic myelofibrosis (MF) and found that high molecular risk mutations, intermediate 2/high Dynamic International Prognostic Score System, and intermediate 2/high Myelofibrosis Secondary to Polycythemia Vera and Essential Thrombocythemia Prognostic Model were associated with cytopenic MF. Patients with cytopenia received lower doses of ruxolitinib and had worse treatment outcomes, suggesting the need for alternative therapeutic strategies.
Letter
Oncology
Francesca Palandri, Elena M. Elli, Giuseppe Auteri, Massimiliano Bonifacio, Giulia Benevolo, Florian H. Heidel, Simona Paglia, Malgorzata M. Trawinska, Costanza Bosi, Elena Rossi, Mario Tiribelli, Alessia Tieghi, Alessandra Iurlo, Nicola Polverelli, Giovanni Caocci, Gianni Binotto, Francesco Cavazzini, Eloise Beggiato, Daniela Cilloni, Caterina Tatarelli, Francesco Mendicino, Maurizio Miglino, Monica Bocchia, Monica Crugnola, Camilla Mazzoni, Andrea D. Romagnoli, Giovanni Rindone, Sara Ceglie, Alessandra D'Addio, Eleonora Santoni, Daniele Cattaneo, Daniela Bartoletti, Roberto M. Lemoli, Mauro Krampera, Antonio Cuneo, Gianpietro C. Semenzato, Roberto Latagliata, Elisabetta Abruzzese, Nicola Vianelli, Michele Cavo, Alessandro Andriani, Valerio De Stefano, Giuseppe A. Palumbo, Massimo Breccia
BLOOD CANCER JOURNAL
(2023)
Article
Genetics & Heredity
Anna Ferrari, Roberto Fiocca, Elena Bonora, Chiara Domizio, Eugenio Fonzi, Davide Angeli, Gian Domenico Raulli, Sandro Mattioli, Giovanni Martinelli, Chiara Molinari
Summary: This study conducted genomic analysis on a neoadjuvant chemotherapy-resistant gastroesophageal tumor and identified a novel gene fusion, MSI2-C17orf64, that has never been reported before. This finding highlights the potential of MSI2 as a therapeutic target.
Article
Oncology
Arianna Orsini, Luca Mastracci, Isotta Bozzarelli, Anna Ferrari, Federica Isidori, Roberto Fiocca, Marialuisa Lugaresi, Antonietta D'Errico, Deborah Malvi, Erica Cataldi-Stagetti, Paola Spaggiari, Anna Tomezzoli, Luca Albarello, Ari Ristimaki, Luca Bottiglieri, Kausilia K. Krishnadath, Riccardo Rosati, Uberto Fumagalli Romario, Giovanni De Manzoni, Jari Rasanen, Giovanni Martinelli, Sandro Mattioli, Elena Bonora
Summary: Esophageal adenocarcinoma (EAC) is a severe malignancy with increasing incidence, poorly understood pathogenesis, and low survival rates. TP53 gene alterations, especially missense mutations, negatively affect cancer-specific survival in EAC. HNF1alpha gene disruption is associated with other gene alterations and is identified as a new EAC-mutated gene.
Review
Oncology
Giuseppe Schepisi, Caterina Gianni, Michela Palleschi, Sara Bleve, Chiara Casadei, Cristian Lolli, Laura Ridolfi, Giovanni Martinelli, Ugo De Giorgi
Summary: To date, various therapeutic strategies, including immunotherapies, have been successful in prolonging the survival of breast cancer patients. Our article focuses on the application of chimeric antigen receptor-based immunotherapy in breast cancer.
Article
Oncology
Francesca Palandri, Haifa Kathrin Al-Ali, Paola Guglielmelli, Mike W. Zuurman, Rajendra Sarkar, Vikas Gupta
Summary: Bone marrow fibrosis (BMF) is a negative prognostic factor for myelofibrosis (MF). The JUMP trial investigated the safety and efficacy of the JAK1/JAK2 inhibitor ruxolitinib in symptomatic MF patients. This post hoc analysis found that patients with low-grade fibrosis (LGF) had better response rates and survival estimates compared to patients with high-grade fibrosis (HGF). Early initiation of ruxolitinib therapy was associated with increased response rates in all patients.
Article
Oncology
Francesca Palandri, Elena Rossi, Giuseppe Auteri, Massimo Breccia, Simona Paglia, Giulia Benevolo, Elena M. Elli, Francesco Cavazzini, Gianni Binotto, Alessia Tieghi, Mario Tiribelli, Florian H. Heidel, Massimiliano Bonifacio, Novella Pugliese, Giovanni Caocci, Monica Crugnola, Francesco Mendicino, Alessandra D'Addio, Simona Tomassetti, Bruno Martino, Nicola Polverelli, Sara Ceglie, Camilla Mazzoni, Rikard Mullai, Alessia Ripamonti, Bruno Garibaldi, Fabrizio Pane, Antonio Cuneo, Mauro Krampera, Gianpietro Semenzato, Roberto M. Lemoli, Nicola Vianelli, Giuseppe A. Palumbo, Alessandro Andriani, Michele Cavo, Roberto Latagliata, Valerio De Stefano
Summary: The prognostic relevance of complete response to hydroxyurea, predictors of response, and patients' triggers for switching to ruxolitinib in polycythemia vera are uncertain. Many PV patients receive underdosed hydroxyurea, leading to lower response and toxicity rates. Splenomegaly and other symptoms are the main drivers for early switch to ruxolitinib despite poor response to hydroxyurea.
Article
Oncology
Francesca Palandri, Giuseppe A. Palumbo, Massimiliano Bonifacio, Elena M. Elli, Mario Tiribelli, Giuseppe Auteri, Malgorzata M. Trawinska, Nicola Polverelli, Giulia Benevolo, Alessia Tieghi, Fabrizio Cavalca, Giovanni Caocci, Eloise Beggiato, Gianni Binotto, Francesco Cavazzini, Maurizio Miglino, Costanza Bosi, Monica Crugnola, Monica Bocchia, Bruno Martino, Novella Pugliese, Marta Venturi, Alessandro Isidori, Daniele Cattaneo, Mauro Krampera, Fabrizio Pane, Daniela Cilloni, Gianpietro Semenzato, Roberto M. Lemoli, Antonio Cuneo, Elisabetta Abruzzese, Filippo Branzanti, Nicola Vianelli, Michele Cavo, Florian Heidel, Alessandra Iurlo, Massimo Breccia
Summary: Predictors of early discontinuation of ruxolitinib therapy and death on therapy were investigated in patients with myelofibrosis. Low platelet and hemoglobin levels, primary myelofibrosis, no spleen response at 3 months, and low starting dose of ruxolitinib were associated with a higher probability of therapy failure. A predictive model was built to identify patients at higher risk of failure with ruxolitinib monotherapy, who should consider alternative frontline strategies.
Review
Hematology
Patrice Nasnas, Claudio Cerchione, Gerardo Musuraca, Giovanni Martinelli, Alessandra Ferrajoli
Summary: Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by the uncontrolled proliferation of mature B lymphocytes. Targeted therapies, including BTK inhibitors and BCL2 inhibitors, have become the standard of care for CLL treatment in the United States and Europe. These therapies have a good safety profile overall, but can also have unique toxicities.
HEMATOLOGY REPORTS
(2023)