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
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
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
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
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)
Review
Cell Biology
Jiale Ma, Shan Chen, Yanqing Huang, Jie Zi, Jinlong Ma, Zheng Ge
Summary: The case report describes a rare instance of a patient with MPL-mutated essential thrombocythemia developing into Philadelphia positive B lymphoblastic leukemia after 13 years. Treatment with a new tyrosine kinase inhibitor led to remission, but the patient eventually relapsed. This case provides evidence on the clonal relationship of myeloproliferative neoplasms and post-MPN acute lymphoblastic leukemia.
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
Biochemistry & Molecular Biology
Maysam Basim Najm, Sana Dlawar Jalal, Hisham Arif Getta
Summary: This study investigated the mutation of JAK2, CALR, and MPL genes as diagnostic and prognostic biomarkers in patients with myeloproliferative neoplasms in the Kurdistan region of Iraq. The results showed significant associations between these mutations and disease prognosis and diagnosis.
CELLULAR AND MOLECULAR BIOLOGY
(2022)
Article
Genetics & Heredity
Tatiana Makarik, Adhamjon O. Abdullaev, Elena E. Nikulina, Svetlana A. Treglazova, Elena E. Stepanova, Irina N. Subortseva, Alla M. Kovrigina, Anait L. Melikyan, Sergei M. Kulikov, Andrey B. Sudarikov
Summary: JAK2 V617F, CALR exon 9, and MPL exon 10 mutations are commonly associated with Ph-negative chronic myeloproliferative neoplasms. Despite lacking selective advantage for clonal expansion after one mutation emerges, simultaneous findings of these mutations have been reported in a small percentage of cases.
Article
Pathology
Ming-Chung Kuo, Wen-Yu Chuang, Hung Chang, Tung-Huei Lin, Jin-Hou Wu, Tung-Liang Lin, Che-Wei Ou, Yu-Shin Hung, Ting-Yu Huang, Ying-Jung Huang, Po-Nan Wang, Lee-Yung Shih
Summary: This study aimed to investigate the clinical and prognostic relevance of distinguishing pre-PMF-T from ET. Results showed that pre-PMF-T patients had older age, higher leukocyte and platelet counts, but lower hemoglobin levels compared to ET patients. Pre-PMF-T patients had lower overall, leukemia-free, and thrombosis-free survival rates. The presence of JAK2 (V617F) mutation was significantly associated with pre-PMF-T.
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
(2023)
Review
Medicine, General & Internal
Sholhui Park, Min-Kyung So, Min-Sun Cho, Dae-Young Kim, Jungwon Huh
Summary: Primary myelofibrosis (PMF) and paroxysmal nocturnal hemoglobinuria (PNH) are rare diseases, and having both at the same time is uncommon. A case with PMF and PNH with JAK2 V617F, U2AF1 and SETBP1 mutations is reported, highlighting the complex nature of these diseases and genetic mutations. Further research is needed to fully understand the clinical significance and genetic associations of the mutations found in this patient.
Article
Hematology
Wenjuan Fan, Weijie Cao, Jianxiang Shi, Fengcai Gao, Meng Wang, Linping Xu, Fang Wang, Yingmei Li, Rong Guo, Zhilei Bian, Wei Li, Zhongxing Jiang, Wang Ma
Summary: The classic BCR-ABL1-negative myeloproliferative neoplasm (MPN) is a highly heterogeneous hematologic tumor that includes three subtypes. This study aimed to clarify the role of bone marrow (BM) monocytes/macrophages in MPN patients with the JAK2(V617F) mutation. The findings provide important resources for future studies and targets for the treatment of MPN patients.
ANNALS OF HEMATOLOGY
(2023)
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
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.
Review
Cell Biology
Frederike Kramer, Ann Mullally
Summary: Mutations in calreticulin are important in the development of myeloproliferative neoplasms (MPN). These mutations result in a novel C-terminus of calreticulin that binds abnormally to the thrombopoietin receptor MPL. This surface antigen has become a target for immunotherapy in MPN. Recent advances in the development of mutant calreticulin targeting antibodies for MPN are summarized here.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2023)
