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)
Article
Cell & Tissue Engineering
Jingyuan Tong, Ting Sun, Shihui Ma, Yanhong Zhao, Mankai Ju, Yuchen Gao, Ping Zhu, Puwen Tan, Rongfeng Fu, Anqi Zhang, Ding Wang, Di Wang, Zhijian Xiao, Jiaxi Zhou, Renchi Yang, Stephen J. Loughran, Juan Li, Anthony R. Green, Emery H. Bresnick, Dong Wang, Tao Cheng, Lei Zhang, Lihong Shi
Summary: This study demonstrates that in JAK2V617F(+) ET patients, the Mk-primed HSC subpopulation significantly expands with enhanced potential, and during treatment, mutant HSCs are preferentially targeted in this subpopulation. Homozygous mutant HSCs are forced to re-enter quiescence, while their heterozygous counterparts undergo apoptosis.
Article
Hematology
Jan Stetka, Marc Usart, Lucia Kubovcakova, Shivam Rai, Tata Nageswara Rao, Joshua Sutter, Hui Hao-Shen, Stefan Dirnhofer, Florian Geier, Michael S. Bader, Jakob R. Passweg, Vania Manolova, Franz Durrenberger, Nouraiz Ahmed, Timm Schroeder, Tomas Ganz, Elizabeta Nemeth, Laura Silvestri, Antonella Nai, Clara Camaschella, Radek C. Skoda
Summary: JAK2-V617F mutation causes myeloproliferative neoplasms (MPNs) that manifest as polycythemia vera (PV), essential thrombocythemia (ET), or primary myelofibrosis. Iron deficiency is already present in PV patients at diagnosis, while ET patients have normal iron stores. Mice models with JAK2-V617F mutation exhibit iron deficiency in the PV-like phenotype but normal iron stores in the ET-like phenotype. Alterations in iron availability mainly affect premegakaryocyte-erythrocyte progenitors in JAK2-mutant mice. Ferroportin inhibitors and minihepcidins show potential for treating PV patients.
Article
Biochemistry & Molecular Biology
Nikola Slaninova, Iveta Bryjova, Zenon Lasota, Radmila Richterova, Jan Kubicek, Martin Augustynek, Ayan Seal, Ondrej Krejcar, Antonino Proto
Summary: This work analyzes the research results on the genetic hematological risks associated with secondary polyglobulia. The study focuses on identifying key markers for diagnosing high-risk patients and excluding less important markers. The results can be used as clinical guidelines for diagnosing parameters with high sensitivity and specificity.
Article
Medicine, General & Internal
Emina Babarovic, Blazen Marijic, Luka Vranic, Josipa Ban, Toni Valkovic, Ita Hadzisejdic
Summary: Cases with low level JAK2 V617F mutations may present with normal looking megakaryocytes without atypia, while those with high JAK2 V617F mutation burden often have atypical megakaryocytes with clustering and maturation defects. Platelet count and hematocrit levels differ significantly between JAK2 V617F <3% and ≥3% mutation burden. Close follow-up is necessary for patients with low JAK2 V617F positivity due to the morphological changes observed in the bone marrow.
Article
Multidisciplinary Sciences
Stella Pearson, Rognvald Blance, Fei Yan, Ya-Ching Hsieh, Bethany Geary, Fabio M. R. Amaral, Tim C. P. Somervaille, Kristina Kirschner, Anthony D. D. Whetton, Andrew Pierce
Summary: Myelofibrosis is a neoplasm that affects the bone marrow and results in reduced life quality and length. Existing drugs provide some benefit, but there is a need for new therapies to better treat myelofibrosis. By re-analyzing proteomic data, researchers identified CBL0137 as a potential drug to target Jak2 mutation-driven malignancies.
Article
Multidisciplinary Sciences
Chartsiam Tipgomut, Archrob Khuhapinant, Marieangela C. Wilson, Saiphon Poldee, Kate J. Heesom, Chanatip Metheetrairut, Orapan Sripichai, Chalermchai Mitrpant, Jan Frayne, Kongtana Trakarnsanga
Summary: This study identified 17 differentially expressed proteins in erythroblasts of PV patients compared to healthy subjects, including MTAP. The abnormal expression of these proteins may be related to the pathology of PV.
SCIENTIFIC REPORTS
(2021)
Review
Hematology
Dina Mahdi, Jessica Spiers, Alexandros Rampotas, Nicola Polverelli, Donal P. P. McLornan
Summary: Management approaches for accelerated and blast phase myeloproliferative neoplasms remain challenging, and current therapeutic outcomes for non-transplant eligible patients are poor. There is currently no specific predictive signature for the risk and timing of transformation, causing anxiety among patients and clinicians. This review provides an up-to-date understanding of the pathogenesis, discusses current therapies and outcomes, and explores the potential impact of novel agents.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Naseema Gangat, Paola Guglielmelli, Silvia Betti, Faiqa Farrukh, Alessandra Carobbio, Tiziano Barbui, Alessandro M. Vannucchi, Valerio De Stefano, Ayalew Tefferi
Summary: The study retrospectively reviewed 74 cases of CVT associated with MPNs, revealing a close association with JAK2V617F, younger age, and female gender. MPN-associated CVT had a lower likelihood of concurrent venous thromboses and intracerebral hemorrhage compared to COVID vaccine-related CVT, making it non-fatal.
AMERICAN JOURNAL OF HEMATOLOGY
(2021)
Article
Cell & Tissue Engineering
Debra Van Egeren, Javier Escabi, Maximilian Nguyen, Shichen Liu, Christopher R. Reilly, Sachin Patel, Baransel Kamaz, Maria Kalyva, Daniel J. DeAngelo, Ilene Galinsky, Martha Wadleigh, Eric S. Winer, Marlise R. Luskin, Richard M. Stone, Jacqueline S. Garcia, Gabriela S. Hobbs, Fernando D. Camargo, Franziska Michor, Ann Mullally, Isidro Cortes-Ciriano, Sahand Hormoz
Summary: The JAK2-V617F mutation affects the self-renewal and differentiation dynamics of HSCs in MPNs patients, helping to reconstruct cancer lineages, with the mutation likely occurring several decades before diagnosis and providing a selective advantage for mutant HSCs.
Article
Medicine, General & Internal
Ziqing Wang, Weiyi Liu, Dehao Wang, Erpeng Yang, Yujin Li, Yumeng Li, Yan Sun, Mingjing Wang, Yan Lv, Xiaomei Hu
Summary: Thrombosis is a common complication of myeloproliferative neoplasm (MPN) and understanding the risk factors is important for predicting and preventing thrombotic events. This study found that TET2 mutation and a history of remote thrombosis are independent risk factors for thrombosis in patients with essential thrombocythemia (ET) while the neutrophil-to-lymphocyte ratio (NLR) and a history of remote thrombosis are independent risk factors for thrombosis in patients with polycythemia vera (PV).
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Medicine, General & Internal
Li Xu, Li-Li Lu, Jian-Dong Gao
Summary: This article reports a rare case of polycythemia vera-associated minimal change disease. The patient achieved remission of proteinuria after treatment.
WORLD JOURNAL OF CLINICAL CASES
(2022)
Article
Hematology
Ruochen Jia, Thomas Balligand, Vasyl Atamanyuk, Harini Nivarthi, Erica Xu, Leon Kutzner, Jakob Weinzierl, Audrey Nedelec, Stefan Kubicek, Roman Lesyk, Oleh Zagrijtschuk, Stefan N. Constantinescu, Robert Kralovics
Summary: Targeting the GBD of CALR can inhibit the oncogenicity of mutant CALR, with specific compounds disrupting CALR-MPL interaction and inhibiting the JAK2-STAT5 pathway to selectively kill CALR-mutated cells.
Article
Hematology
Kazuhide Iizuka, Soji Morishita, Yuji Nishizaki, Yoshikazu Iizuka, Noriyoshi Iriyama, Tomonori Ochiai, Naotake Yanagisawa, Hajime Yasuda, Jun Ando, Akihiko Gotoh, Masami Takei, Yoshihiro Hatta, Hideki Nakamura, Tomohiro Nakayama, Norio Komatsu
Summary: von Willebrand factor ristocetin cofactor (vWF activity) and platelet count (PLT) are negatively correlated in patients with polycythemia vera (PV) and essential thrombocythemia (ET). However, vWF activity does not always normalize upon controlling PLT in those patients. A stronger negative correlation between vWF activity and PLT was observed in calreticulin mutation-positive (CALR+) ET than in Janus kinase 2 mutation-positive (JAK2+) PV or ET groups.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2022)
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
Floris C. Loeff, Kevin Rijs, Esther H. M. van Egmond, Willem H. Zoutman, Xiaohang Qiao, Wilhelmina G. M. Kroes, Sabrina A. J. Veld, Marieke Griffioen, Maarten H. Vermeer, Jacques Neefjes, J. H. Frederik Falkenburg, Constantijn J. M. Halkes, Inge Jedema
AMERICAN JOURNAL OF HEMATOLOGY
(2019)
Article
Oncology
Christiaan van Weeghel, Annemijn P. A. Wierenga, Mieke Versluis, Thorbald van Hall, Pieter A. van der Velden, Wilma G. M. Kroes, Ulrich Pfeffer, Gregorius P. M. Luyten, Martine J. Jager
Article
Oncology
Zahra Souri, Annemijn P. A. Wierenga, Christiaan van Weeghel, Pieter A. van Der Velden, Wilma G. M. Kroes, Gregorius P. M. Luyten, Sjoerd H. van Der Burg, Aart G. Jochemsen, Martine J. Jager
Article
Oncology
Wibowo Arindrarto, Daniel M. Borras, Ruben A. L. de Groen, Redmar R. van den Berg, Irene J. Locher, Saskia A. M. E. van Diessen, Rosalie van der Holst, Edith D. van der Meijden, M. Willy Honders, Rick H. de Leeuw, Wina Verlaat, Inge Jedema, Wilma G. M. Kroes, Jeroen Knijnenburg, Tom van Wezel, Joost S. P. Vermaat, Peter J. M. Valk, Bart Janssen, Peter de Knijff, Cornelis A. M. van Bergen, Erik B. van den Akker, Peter A. C. 't Hoen, Szymon M. Kielbasa, Jeroen F. J. Laros, Marieke Griffioen, Hendrik Veelken
Summary: The study established whole transcriptome RNA sequencing as a comprehensive platform for AML diagnostics by developing HAMLET, a bioinformatics pipeline that accurately detects fusion genes, small variants, and tandem duplications. HAMLET has the potential to provide accurate diagnostic information relevant for AML classification, risk assessment, and targeted therapy on a single technology platform.
Article
Multidisciplinary Sciences
Palash C. Maity, Mayas Bilal, Marvyn T. Koning, Marc Young, Cornelis A. M. van Bergen, Valerio Renna, Antonella Nicolo, Moumita Datta, Eva Gentner-Goebel, Rob S. Barendse, Sebastiaan F. Somers, Ruben A. L. de Groen, Joost S. P. Vermaat, Daniela Steinbrecher, Christof Schneider, Eugen Tausch, Tamara Bittolo, Riccardo Bomben, Andrea Nicola Mazzarello, Giovanni del Poeta, Wilma G. M. Kroes, J. Tom van Wezel, Katharina Imkeller, Christian E. Busse, Massimo Degano, Tamam Bakchoul, Axel Ronald Schulz, Henrik Mei, Paolo Ghia, Konstantia Kotta, Kostas Stamatopoulos, Hedda Wardemann, Antonella Zucchetto, Nicholas Chiorazzi, Valter Gattei, Stephan Stilgenbauer, Hendrik Veelken, Hassan Jumaa
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Hematology
Francesco Saettini, Cecilia Poli, Jaime Vengoechea, Sonia Bonanomi, Julio C. Orellana, Grazia Fazio, Fred H. Rodriguez, Loreani P. Noguera, Claire Booth, Valentina Jarur-Chamy, Marissa Shams, Maria Iascone, Maja Vukic, Serena Gasperini, Manuel Quadri, Amairelys Barroeta Seijas, Elizabeth Rivers, Mario Mauri, Raffaele Badolato, Giovanni Cazzaniga, Cristina Bugarin, Giuseppe Gaipa, Wilma G. M. Kroes, Daniele Moratto, Monique M. van Ostaijen-ten Dam, Frank Baas, Silvere van der Maarel, Rocco Piazza, Zeynep H. Coban-Akdemir, James R. Lupski, Bo Yuan, Ivan K. Chinn, Lucia Daxinger, Andrea Biondi
Summary: Agammaglobulinemia, recurrent infections, hypertrophic cardiomyopathy and neutropenia were found in three novel patients in this study. Variants in the gene for folliculin interacting protein 1 (FNIP1) were identified, leading to impaired B-cell metabolism and development. This study highlights the importance of FNIP1 in B-cell development and metabolism.
Article
Oncology
Zahra Souri, Aart G. Jochemsen, Mieke Versluis, Annemijn P. A. Wierenga, Fariba Nemati, Pieter A. van der Velden, Wilma G. M. Kroes, Robert M. Verdijk, Gregorius P. M. Luyten, Martine J. Jager
Article
Oncology
Zahra Souri, Annemijn P. A. Wierenga, Emine Kilic, Erwin Brosens, Stefan Bohringer, Wilma G. M. Kroes, Robert M. Verdijk, Pieter A. van Der Velden, Gregorius P. M. Luyten, Martine J. Jager
Summary: Specific miRNAs are associated with the inflammatory phenotype in uveal melanoma (UM), with differential expression between disomy 3/BAP1-positive and monosomy 3/BAP1-negative UM. This suggests a potential role for BAP1 loss in regulating HLA expression and inflammation through miRNAs in UM.
Article
Oncology
Zahra Souri, Aart G. Jochemsen, Annemijn P. A. Wierenga, Wilma G. M. Kroes, Rob M. Verdijk, Pieter A. van der Velden, Gregorius P. M. Luyten, Martine J. Jager
Summary: In Uveal Melanoma (UM), increased expression of several HDACs is associated with the loss of chromosome 3. This study found a positive correlation between the expression of HDACs 1, 3, and 8 and T-cell infiltrates, while HDACs 2 and 11 were negatively correlated with macrophages. Furthermore, stimulation with interferon-gamma induced an increase in certain HDACs, suggesting a potential link with the loss of chromosome 3/BAP1 and inflammation in UM.
Article
Oncology
Zahra Souri, Annemijn P. A. Wierenga, Wilma G. M. Kroes, Pieter A. van der Velden, Robert M. Verdijk, Michael Eikmans, Gregorius P. M. Luyten, Martine J. Jager
Summary: Uveal melanoma (UM) is a rare ocular malignancy with high-risk features expressing higher levels of LAG3 and its ligands, potentially serving as targets for immunotherapy in UM.
Meeting Abstract
Ophthalmology
Annemijn P. A. Wierenga, Niels J. Brouwer, Robert M. Verdijk, Marc-Henri Stern, Sjoerd G. van Duinen, Wilma G. M. Kroes, Marina Marinkovic, Gregorius P. M. Luyten, Martine J. Jager
ACTA OPHTHALMOLOGICA
(2021)
Meeting Abstract
Ophthalmology
A. P. A. Wierenga, N. J. Brouwer, R. M. Verdijk, S. G. van Duinen, W. G. M. Kroes, M. Marinkovic, G. P. M. Luyten, M. J. Jager
ACTA OPHTHALMOLOGICA
(2020)
Article
Ophthalmology
Mehmet Dogrusoz, Niels J. Brouwer, Stefan J. R. de Geus, Long Ly, Stefan Bohringer, Sjoerd G. van Duinen, Wilma G. M. Kroes, Pieter A. van der Velden, Geert W. Haasnoot, Marina Marinkovic, Gregorius P. M. Luyten, Tero T. Kivela, Martine J. Jager
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2020)
Article
Ophthalmology
Annemijn P. A. Wierenga, Jinfeng Cao, Henk Mouthaan, Christiaan van Weeghel, Robert M. Verdijk, Sjoerd G. van Duinen, Wilma G. M. Kroes, Mehmet Dogrusoz, Marina Marinkovic, Sjoerd S. H. van der Burg, Gregorius P. M. Luyten, Martine J. Jager
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2019)
Meeting Abstract
Genetics & Heredity
Esther Nibbeling, Roos Klinkenberg, Corine Buitenhuis, Marlies Hogenboom, Peter van Balen, Wilma Kroes
MOLECULAR CYTOGENETICS
(2019)