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)
Review
Hematology
Andrew T. Kuykendall
Summary: Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by activating mutations in Janus kinase 2, erythrocytosis, and bone marrow hypercellularity. The goals of treatment are to achieve control of hematocrit and blood counts to reduce the risk of thrombohemorrhagic events and improve PV-related symptoms. First-line treatment typically involves cytoreduction with hydroxyurea or interferon formulations, but inadequate response or intolerance may require second-line treatments such as ruxolitinib. This review outlines preferred treatment and patient management strategies for PV patients who do not respond adequately to or cannot tolerate first-line treatment.
ANNALS OF HEMATOLOGY
(2023)
Article
Hematology
Andrew L. Sochacki, Cosmin Adrian Bejan, Shilin Zhao, Ameet Patel, Ashwin Kishtagari, Travis P. Spaulding, Alexander J. Silver, Shannon S. Stockton, Kelly Pugh, R. Dixon Dorand, Manasa Bhatta, Nicholas Strayer, Siwei Zhang, Christina A. Snider, Thomas Stricker, Aziz Nazha, Alexander G. Bick, Yaomin Xu, Michael R. Savona
Summary: Treatment decisions in primary myelofibrosis are usually determined by various prognostic systems, but they do not routinely incorporate patient-specific comorbidities. In this study, the impact of comorbidities on survival was assessed, and it was found that specific comorbidities were associated with inferior survival in primary myelofibrosis patients. By including comorbidities in the risk evaluation, the prognostic capability of genetics-based scoring systems could be enhanced.
Article
Public, Environmental & Occupational Health
Faisal A. A. Nawaz, Mehr Muhamad Adeel Riaz, Christos Tsagkaris, Umme H. H. Faisal, Elisabeth Klager, Maria Kletecka-Pulker, Oliver Kimberger, Harald Willschke, Nagina Khan, Meshal A. A. Sultan, Atanas G. G. Atanasov
Summary: This study evaluates the impact of tweets related to psychiatry using the hashtag #PsychTwitter. The results show that #PsychTwitter generated 125,297 tweets shared by 40,058 Twitter users, with a total of 492,565,230 impressions. The most active contributors were doctors, advocacy organizations, and researchers/academics. The top countries for tweets with #PsychTwitter were the United States, the United Kingdom, Canada, India, and Australia, indicating that Twitter is a widely used platform for mental health discussions.
FRONTIERS IN PUBLIC HEALTH
(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.
Review
Genetics & Heredity
Mathilde Regimbeau, Romain Mary, Francois Hermetet, Francois Girodon
Summary: Polycythemia vera is a myeloproliferative neoplasm characterized by alterations in the JAK2 gene and other genetic mutations. Understanding the complex genomic landscape of PV has led to the identification of potential therapeutic strategies for patients.
Editorial Material
Oncology
Rupali R. Bhave, Ruben Mesa, Michael R. Grunwald
Summary: The rapid pace of drug development in hematology has led to multiple approvals for myelofibrosis (MF) and polycythemia vera (PV) in recent years. There are also many innovative agents and combinations being explored for myeloproliferative neoplasms (MPNs). In the past year, there have been advances in MF, PV, and essential thrombocythemia, focusing on strategies to optimize inhibition of signal transduction, modify epigenetics, enhance apoptosis, target DNA replication, transform host immunity, and alter the tumor microenvironment. The increased focus on MPNs brings hope for improving morbidity and mortality in this group of diseases.
Article
Oncology
Nicole Kucine, Shayla Bergmann, Spencer Krichevsky, Devin Jones, Michael Rytting, Juhi Jain, Carolyn M. Bennett, Linda M. S. Resar, John Mascarenhas, Srdan Verstovsek, Ronald Hoffman
Summary: MPN are rare disorders in young patients without standardized treatment recommendations. Interferon is suggested as upfront therapy in young patients with MPN, as it effectively controls extreme thrombocytosis and is tolerated by many. Prospective studies evaluating interferon in young MPN patients are needed.
PEDIATRIC BLOOD & CANCER
(2021)
Article
Pathology
Christopher M. Sande, Guang Yang, Ayman Mohamed, Ben L. Legendre, Danielle Pion, Stephanie L. Ferro, Kate Grimm, Kojo S. J. Elenitoba-Johnson
Summary: This study developed a PCR and high-resolution melting (HRM) analysis-based assay for simultaneous evaluation of genetic alterations in JAK2, MPL and CALR, which are crucial for the diagnosis of Philadelphia-negative myeloproliferative neoplasms. The HRM-based assay showed high accuracy, sensitivity and specificity compared to Sanger sequencing, making it a powerful tool for rapid detection of clinically relevant disease variants.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
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
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)
Review
Biochemistry & Molecular Biology
Vincenzo Fiorentino, Pietro Tralongo, Maurizio Martini, Silvia Betti, Elena Rossi, Francesco Pierconti, Valerio De Stefano, Luigi Maria Larocca
Summary: Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are a group of blood disorders, with some cases rapidly progressing to myelofibrotic bone marrow failure. Abnormalities in the megakaryocyte lineage play a crucial role in this progression. This review analyzes prognostic factors for MPNs evolving into myelofibrotic bone marrow failure and discusses the role of the megakaryocytic lineage in different stages of MPNs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Public, Environmental & Occupational Health
Faisal A. Nawaz, Austin A. Barr, Monali Y. Desai, Christos Tsagkaris, Romil Singh, Elisabeth Klager, Fabian Eibensteiner, Emil D. Parvanov, Mojca Hribersek, Maria Kletecka-Pulker, Harald Willschke, Atanas G. Atanasov
Summary: AI has the potential to reshape medical practice and healthcare delivery. Online discussions on this topic are increasing, but many practitioners and medical students have limited understanding of AI. To promote research and resources on the intersection of AI and medicine, a Twitter-based campaign using the hashtag #MedTwitterAI was created. The analysis of tweets with the hashtag revealed significant interest and engagement from a diverse and global audience, demonstrating the effectiveness of hashtags in raising awareness and facilitating knowledge-sharing.
FRONTIERS IN PUBLIC HEALTH
(2022)
Review
Hematology
Sevastianos Chatzidavid, Nefeli Giannakopoulou, Panagiotis Theodorou Diamantopoulos, Eleni Gavriilaki, Panagiota Katsiampoura, Eleftheria Lakiotaki, Stratigoula Sakellariou, Nora-Athina Viniou, Georgios Dryllis
Summary: This case report presents a rare case of a patient with coexistence of PNH clones and a JAK2V617F positive PV, experiencing unusual thromboses without hemolysis.
THROMBOSIS JOURNAL
(2021)
Article
Pharmacology & Pharmacy
M. -L. Chen, H. -C. Zhang, E. -P. Yang
Summary: This study provides new ideas for the scientific research of myeloproliferative neoplasm (MPN) by systematically combing the literature. The research mainly focuses on the occurrence and progress mechanism of MPN, clinical significance of non-driving gene mutation, optimization of thromboprophylaxis, clinical research of long-acting interferon and JAK2 inhibitors, and exploration of better therapies for myelofibrosis and post-MPN acute myeloid leukemia.
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
(2023)
Review
Oncology
Moshe Talpaz, Jean-Jacques Kiladjian
Summary: Myelofibrosis is a serious bone marrow disorder characterized by splenomegaly, and Fedratinib, a selective JAK2 inhibitor, has shown promising results in treating MF patients by targeting the JAK/STAT signaling pathway.
Letter
Gastroenterology & Hepatology
Jean-Jacques Kiladjian, Pierre-Edouard Debureaux, Aurelie Plessier, Juliette Soret-Dulphy, Dominique Valla, Bruno Cassinat, Pierre-Emmanuel Rautou
JOURNAL OF HEPATOLOGY
(2021)
Article
Health Care Sciences & Services
Lucas Oliveira J. E. Silva, Graciela Maldonado, Tara Brigham, Aidan F. Mullan, Audun Utengen, Daniel Cabrera
Summary: This study revealed a weak positive correlation between a novel author-level complementary metric and the h-index, suggesting a bridge between the traditional citation metrics and novel social media-based metrics.
JOURNAL OF MEDICAL INTERNET RESEARCH
(2021)
Article
Hematology
Nabih Maslah, Odonchimeg Ravdan, Louis Drevon, Emmanuelle Verger, Celia Belkhodja, Christine Chomienne, Bruno Cassinat, Jean-Jacques Kiladjian, Stephane Giraudier, Marie-Helene Schlageter
Summary: This study evaluated the diagnostic performances of erythropoietin and JAK2 mutations in patients suspected of polycythemia, finding that low erythropoietin levels and JAK2 mutations have comparable positive predictive values for true polycythemia.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Cell Biology
Ralfs Buks, Tracy Dagher, Maria Giustina Rotordam, David Monedero Alonso, Sylvie Cochet, Emilie-Fleur Gautier, Philippe Chafey, Bruno Cassinat, Jean-Jacques Kiladjian, Nadine Becker, Isabelle Plo, Stephane Egee, Wassim El Nemer
Summary: The research reveals that there are elevated levels of multiple calcium binding proteins as well as endoplasmic-reticulum-residing proteins in the red blood cell membranes of patients with Polycythemia Vera (PV). Moreover, the study also indicates that the JAK2(V617F) mutation has an impact on calcium homeostasis and red blood cell ion channel activity.
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)
Letter
Oncology
Jean-Jacques Kiladjian, Christoph Klade, Pencho Georgiev, Dorota Krochmalczyk, Liana Gercheva-Kyuchukova, Miklos Egyed, Petr Dulicek, Arpad Illes, Halyna Pylypenko, Lylia Sivcheva, Jiri Mayer, Vera Yablokova, Kurt Krejcy, Victoria Empson, Hans C. Hasselbalch, Robert Kralovics, Heinz Gisslinger
Article
Oncology
Claire N. Harrison, Vikas K. Gupta, Aaron T. Gerds, Raajit Rampal, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew T. Kuykendall, Alessandro M. Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larran, Andrea Patriarca, Marina Kremyanskaya, Adam J. Mead, Sanjay Akhani, Yuri Sheikine, Gozde Colak, John Mascarenhas
Summary: Myelofibrosis (MF) is a rare type of blood cancer that leads to scarring in the bone marrow and a lack of healthy blood cell production. The current standard treatment, ruxolitinib, has limited efficacy in improving symptoms long term. Pelabresib is a new drug being developed for MF. This article describes the design of the ongoing MANIFEST-2 study, which is evaluating the effectiveness and safety of pelabresib and ruxolitinib compared to placebo and ruxolitinib in MF patients.
Article
Oncology
Ruben Mesa, Claire Harrison, Stephen T. Oh, Aaron T. Gerds, Vikas Gupta, John Catalano, Francisco Cervantes, Timothy Devos, Marek Hus, Jean-Jacques Kiladjian, Ewa Lech-Maranda, Donal McLornan, Alessandro M. Vannucchi, Uwe Platzbecker, Mei Huang, Bryan Strouse, Barbara Klencke, Srdan Verstovsek
Summary: JAK inhibitors are effective for myelofibrosis, but do not address anemia. Momelotinib, targeting ACVR1/ALK2, JAK1 and JAK2, shows activity against anemia, symptoms, and splenomegaly.
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.
Review
Hematology
Jean-Jacques Kiladjian, Bruno Cassinat
Summary: Myeloproliferative neoplasms (MPNs) are a common cause of primary splanchnic vein thrombosis, present in about 40% of patients. Diagnosis can be challenging due to confounding factors like portal hypertension or bleeding complications. However, improved diagnostic tools, including molecular markers, have helped in accurate diagnosis and prognosis estimation. A multidisciplinary approach is crucial to determine the subtype and recommend appropriate tests and treatment strategies for patients with splanchnic vein thrombosis and MPNs.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Review
Oncology
Nabih Maslah, Lina Benajiba, Stephane Giraudier, Jean-Jacques Kiladjian, Bruno Cassinat
Summary: Myeloproliferative neoplasms are characterized by driver mutations targeting the JAK/STAT pathway and often display additional mutations targeting various pathways. The disease progression typically involves a chronic phase followed by an accelerated phase or transformation into more aggressive diseases. Recent studies have shed light on the rates and mechanisms of mutation acquisition and selection in hematopoietic cells, using novel techniques to decipher clonal architecture and mutation-induced cell modifications at the single cell level.
Article
Hematology
Vikas Gupta, John Mascarenhas, Marina Kremyanskaya, Raajit K. Rampal, Moshe Talpaz, Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Srdan Verstovsek, Gozde Colak, Debarshi Dey, Claire Harrison
Summary: A study suggests that pelabresib in combination with ruxolitinib may have higher efficacy in treating JAKi treatment-naive MF patients compared to JAKi monotherapy, with significant improvements in spleen volume reduction and total symptom scores.
Article
Hematology
Regis Peffault de Latour, Jeff Szer, Ilene C. Weitz, Alexander Roth, Britta Hochsmann, Jens Panse, Kensuke Usuki, Morag Griffin, Jean-Jacques Kiladjian, Carlos M. de Castro, Hisakazu Nishimori, Temitayo Ajayi, Mohammed Al-Adhami, Pascal Deschatelets, Cedric Francois, Federico Grossi, Antonio M. Risitano, Peter Hillmen
Summary: The PEGASUS trial demonstrated the long-term efficacy and safety of pegcetacoplan in improving outcomes for patients with paroxysmal nocturnal haemoglobinuria. Both treatment groups showed significant improvements in haemoglobin concentration and quality of life, indicating the potential of pegcetacoplan as a therapeutic option.
LANCET HAEMATOLOGY
(2022)
Article
Hematology
Nabih Maslah, Emmanuelle Verger, Stephane Giraudier, Mathias Chea, Ronald Hoffman, John Mascarenhas, Bruno Cassiant, Jean-Jacques Kiladjian
Summary: This study demonstrates the direct effect of MDM2 inhibition on the selection of MPN patients' cells harboring TP53 mutations. TP53 mutations are late events in MPN, mainly occurring in the driver clone, and clonal evolution frequently consists of sequential branching instead of linear consecutive acquisition of mutations in the same clone.