Article
Oncology
Mariarita Sciume, Giusy Ceparano, Cristina Eller-Vainicher, Sonia Fabris, Silvia Lonati, Giorgio Alberto Croci, Luca Baldini, Federica Irene Grifoni
Summary: Systemic mastocytosis (SM) is a rare neoplasm with heterogeneous clinical features, requiring individualized treatment. A patient with indolent SM developed a myeloid neoplasm with PDGFRA rearrangement, achieving complete remission with low-dose imatinib treatment.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Byung-Sik Cho, Gi-June Min, Sung-Soo Park, Silvia Park, Young-Woo Jeon, Seung-Hwan Shin, Seung-Ah Yahng, Jae-Ho Yoon, Sung-Eun Lee, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong Wook-Lee, Myung-Shin Kim, Yong-Goo Kim, Hee-Je Kim
Summary: The prognostic impact of KIT mutations and MRD monitoring for AML with RUNX1-RUNX1T1 following HSCT remains controversial. This retrospective study showed that D816V KIT mutation was associated with post-transplant relapse and poor survival, and pre- and post-transplant MRD assessments were useful for predicting outcomes. Different transplant strategies may be more beneficial based on D816V KIT mutation and pre-transplant MRD status.
Editorial Material
Hematology
Jason Gotlib, Andreas Reiter, Daniel J. DeAngelo
Summary: Avapritinib, a highly selective inhibitor of KIT D816V, has been approved for the treatment of advanced systemic mastocytosis (AdvSM). Clinical trials have shown that avapritinib can induce complete and durable responses in patients with AdvSM, including molecular remission of KIT D816V. However, managing the complex mutational landscape of AdvSM, often accompanied by hematologic neoplasms, poses challenges.
Article
Hematology
Nicole Naumann, Johannes Lubke, William Shomali, Lukas Reiter, Hans-Peter Horny, Mohamad Jawhar, Vito Dangelo, Alice Fabarius, Georgia Metzgeroth, Sebastian Kreil, Karl Sotlar, Claire Oni, Claire Harrison, Wolf-Karsten Hofmann, Nicholas C. P. Cross, Peter Valent, Deepti Radia, Jason Gotlib, Andreas Reiter, Juliana Schwaab
Summary: 45 patients with myeloid neoplasms and concurrent JAK2 V617F and KIT D816V mutations were studied, showing overlapping clinical features and discordant development of variant allele frequency for both mutations. The overall survival of patients without additional high-risk mutations was 77% at 5 years, indicating a fundamentally different prognosis compared to the impact of additional mutations in the individual disorders.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Seiichiro Katagiri, SungGi Chi, Yosuke Minami, Kentaro Fukushima, Hirohiko Shibayama, Naoko Hosono, Takahiro Yamauchi, Takanobu Morishita, Takeshi Kondo, Masamitsu Yanada, Kazuhito Yamamoto, Junya Kuroda, Kensuke Usuki, Daigo Akahane, Akihiko Gotoh
Summary: This paper discusses the role of KIT mutations and the potential of precision medicine in acute myeloid leukemia (AML). New therapies targeting KIT mutations show promise as effective treatments for AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Hematology
Stefan G. C. Mestrum, Anton H. N. Hopman, Frans C. S. Ramaekers, Math P. G. Leers
Summary: The standardization of leukocyte differentiation markers in flow cytometry by the EuroFlow Consortium has advanced the classification of leukemia and lymphoma. This review discusses the potential for incorporating proliferative and apoptotic markers into the diagnosis of myeloid malignancies, emphasizing their diagnostic and prognostic value. Recent developments in multiparameter flow cytometry have enabled quantification of these indicators in myeloid cells during different maturation stages, leading to a better understanding of the biology and pathogenesis of these malignancies.
Article
Oncology
Nevine F. Shafik, Dalia Ibraheem, Marwa Mahmoud Selim, Rasha Mahmoud Allam, Lamiaa A. Fathalla
Summary: C-KIT mutations are common in core binding factor acute myeloid leukemia and have a significant impact on the prognosis of pediatric patients, but not on adult patients.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2022)
Article
Cell Biology
Ghizlane Choukrani, Nienke Visser, Natasha Ustyanovska Avtenyuk, Mirjam Olthuis, Glenn Marsman, Emanuele Ammatuna, Harm Jan Lourens, Toshiro Niki, Gerwin Huls, Edwin Bremer, Valerie R. Wiersma
Summary: AML is a malignancy associated with poor survival rates, especially due to therapy-resistant relapse. The glycan-binding protein Gal-9 has shown tumor-selective cytotoxicity, dependent on autophagy inhibition, making it a potential therapeutic option for AML. In this study, Gal-9 was found to be cytotoxic for AML cells, including stem cells, and showed efficacy in AraC-resistant AML cases. It also enhanced the cytotoxic effect of Azacytidine, providing a possible treatment approach for AML patients not eligible for intensive AraC treatment.
CELL DEATH DISCOVERY
(2023)
Article
Hematology
Koji Sasaki, Shinichi Tsujimoto, Mayuko Miyake, Yuri Uchiyama, Junji Ikeda, Masahiro Yoshitomi, Yuko Shimosato, Mayu Tokumasu, Hidemasa Matsuo, Kenichi Yoshida, Kentaro Ohki, Taeko Kaburagi, Genki Yamato, Yusuke Hara, Masanobu Takeuchi, Akitoshi Kinoshita, Daisuke Tomizawa, Takashi Taga, Souichi Adachi, Akio Tawa, Keizo Horibe, Yasuhide Hayashi, Naomichi Matsumoto, Shuichi Ito, Norio Shiba
Summary: In this study, KIT D816V mutation was identified as a risk factor for relapse in pediatric patients with RUNX1-RUNX1T1-positive AML, leading to significantly inferior 5 year event-free survival compared to those without the mutation. The presence of KIT D816V minor clones in patients with CBF-AML was confirmed, highlighting the importance of examining these minor clones for prognostic evaluation.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Oncology
Junying Wu, Yudi Zhang, Tiejun Qin, Zefeng Xu, Shiqiang Qu, Lijuan Pan, Bing Li, Yujiao Jia, Chengwen Li, Huijun Wang, Qingyan Gao, Wenyu Cai, Jingye Gong, Songyang Zhao, Fuhui Li, Robert Peter Gale, Zhijian Xiao
Summary: This study compared the survival prediction accuracy of two risk models, IPSS-R and IPSS-M, in 852 patients with myelodysplastic syndromes. It found that IPSS-M showed higher accuracy in predicting survival in patients aged 60 and above, possibly due to a higher frequency of mutations related to survival in this age group.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2022)
Article
Oncology
Laura Urwanisch, Michael Stefan Unger, Helene Sieberer, Hieu-Hoa Dang, Theresa Neuper, Christof Regl, Julia Vetter, Susanne Schaller, Stephan M. Winkler, Emanuela Kerschbamer, Christian X. Weichenberger, Peter W. Krenn, Michela Luciano, Lisa Pleyer, Richard Greil, Christian G. Huber, Fritz Aberger, Jutta Horejs-Hoeck
Summary: Epigenetic alterations play a significant role in cancer development, and the reversible nature of epigenetic changes makes them attractive targets for therapy. In this study, the authors investigated the expression of HDAC genes in AML patients and cell lines, and the effects of the HDAC inhibitor TMP269 on AML cells. They found significant overexpression of various HDACs in AML and observed that TMP269 treatment had effects on the proteome and growth of AML cells. Additionally, they demonstrated that the combination of TMP269 and venetoclax resulted in enhanced cell apoptosis. These findings highlight the potential of TMP269 as a therapeutic compound for AML.
Article
Multidisciplinary Sciences
Afia Muhammad Akram, Mubashir Hassan, Asma Chaudhary, Sikandar Hayat, Qurban Ali, Taha Hussain, Amjad Zafar, Muhammad Arshad Javed
Summary: This study aimed to detect nucleotide alterations in newly diagnosed acute myeloid leukemia patients, particularly in the c-kit gene. The analysis revealed a high incidence of mutations in the gene and significant differences between mutant and non-mutant patients in terms of certain clinical and hematological parameters. The study also emphasized the potential damage caused by these mutations to the structure and function of the c-kit protein. Overall, it highlights the importance of screening for c-kit gene alterations in both CBF-AML and cytogenetically normal AML patients.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Zheng Li, Jun Wang, Shuai-Shuai Ge, Qiao-Cheng Qiu, Jia-Hui Du, Shuang-Shuang Shan, Xiang-Dong Shen, Chao-Ling Wan, Bin-Ru Wang, De-Pei Wu, Hui-Ying Qiu, Sheng-Li Xue
Summary: This study reports for the first time the potential therapeutic effect of venetoclax+midostaurin as a new combination therapy for relapsed t(8;21) AMLs with KIT mutations, showing resistance to venetoclax+AZA therapy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Nur Sebnem Ersoz, Aysun Adan
Summary: Resveratrol inhibits the growth of FLT3-ITD AML cells by modulating the activity of ceramide catabolism enzymes. It downregulates the expression of sphingosine kinase and glucosylceramide synthase, leading to inhibition of cell proliferation. Additionally, resveratrol induces apoptosis and arrests the cell cycle in leukemia cells. Combination with other inhibitors enhances its anti-cancer effects.
Article
Allergy
Leander P. De Puysseleyr, Didier G. Ebo, Jessy Elst, Margaretha A. Faber, Marie-Line Van der Poorten, Athina L. Van Gasse, Chris H. Bridts, Christel Mertens, Michel Van Houdt, Margo M. Hagendorens, Anke Verlinden, Katrien Vermeulen, Marie-Berthe Maes, Zwi N. Berneman, Vito Sabato
Summary: In patients with severe anaphylaxis but no mastocytosis in the skin and baseline serum tryptase less than 30 ng/mL, detection of the KIT D816V mutation in peripheral blood may not be very helpful in diagnosing primary mast cell disorders.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2021)