Article
Multidisciplinary Sciences
Yotaro Ochi, Kenichi Yoshida, Ying-Jung Huang, Ming-Chung Kuo, Yasuhito Nannya, Ko Sasaki, Kinuko Mitani, Noriko Hosoya, Nobuhiro Hiramoto, Takayuki Ishikawa, Susan Branford, Naranie Shanmuganathan, Kazuma Ohyashiki, Naoto Takahashi, Tomoiku Takaku, Shun Tsuchiya, Nobuhiro Kanemura, Nobuhiko Nakamura, Yasunori Ueda, Satoshi Yoshihara, Rabindranath Bera, Yusuke Shiozawa, Lanying Zhao, June Takeda, Yosaku Watatani, Rurika Okuda, Hideki Makishima, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Masashi Sanada, Akifumi Takaori-Kondo, Satoru Miyano, Seishi Ogawa, Lee-Yung Shih
Summary: In chronic myeloid leukaemia (CML), the drivers of blast crisis and resistance to tyrosine kinase inhibitors are not fully characterised. Analysis of a cohort of CML samples using genomic technologies reveals that at least one driver alteration is associated with progression and worse prognosis. Genetic abnormalities can help predict clinical outcomes and guide clinical decisions in CML.
NATURE COMMUNICATIONS
(2021)
Article
Pathology
Zelin Zhang, Xianqi Huang, Qi Yan, Yani Lin, Enbin Liu, Yingchang Mi, Shi Liang, Hao Wang, Jun Xu, Kun Ru
Summary: In this study, a model called CMLcGAN was developed for segmenting bone marrow cells, which achieved better performance compared to other segmentation models. By extracting statistical features and conducting clinical validation, the model demonstrated good accuracy in clinical prediction.
AMERICAN JOURNAL OF PATHOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Dragoslava Dikic, Andrija Bogdanovic, Dragana Markovic, Olivera Mitrovic-Ajtic, Tijana Suboticki, Milos Diklic, Milica Vukotic, Teodora Dragojevic, Emilija Zivkovic, Juan F. Santibanez, Vladan P. Cokic
Summary: This study analyzed the relationship between oxidative stress and inflammatory factors in chronic myelogenous leukemia (CML). The results showed increased oxidative stress markers, decreased antioxidant enzyme activity, increased inflammation markers, and decreased anti-inflammatory cytokine levels in CML patients. The study also found enhanced activity of the AKT/mTOR signaling pathway, suggesting that chronic inflammation is involved in the development of CML.
Article
Hematology
Hagop M. Kantarjian, Elias Jabbour, Michael Deininger, Elisabetta Abruzzese, Jane Apperley, Jorge Cortes, Charles Chuah, Daniel J. DeAngelo, John DiPersio, Andreas Hochhaus, Jeffrey Lipton, Franck E. Nicolini, Javier Pinilla-Ibarz, Delphine Rea, Gianantonio Rosti, Philippe Rousselot, Neil P. Shah, Moshe Talpaz, Shouryadeep Srivastava, Xiaowei Ren, Michael Mauro
Summary: Ponatinib has demonstrated deep and durable responses in patients with chronic-phase chronic myeloid leukemia, especially in those resistant to second-generation TKI treatment, and has shown good safety and survival outcomes.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Oncology
Kendra L. Sweet, Jorge E. Cortes, Jane F. Apperley, Mel Mann, Michael J. Mauro, Vivian G. Oehler, Cristina Ruiz, Charles A. Schiffer, Lori A. Ehrlich, Gulsum E. Pamuk, Joseph Wynne, Gautam U. Mehta, R. Angelo de Claro, Marc R. Theoret, B. Douglas Smith, Kelly J. Norsworthy
Summary: The FDA has an accelerated approval program for potentially promising drugs in treating serious conditions. All available treatments for chronic myeloid leukemia (CML) have undergone this program. A group consisting of CML experts, patient panelists, and FDA members gathered to discuss the utility of the accelerated approval program in CML and its future role in drug development, and the results are summarized here.
CLINICAL CANCER RESEARCH
(2023)
Article
Multidisciplinary Sciences
Golnaz Ensieh Kazemi-Sefat, Mohammad Keramatipour, Mohammad Vaezi, Seyed Mohsen Razavi, Kaveh Kavousi, Amin Talebi, Shahrbanoo Rostami, Marjan Yaghmaei, Bahram Chahardouli, Saeed Talebi, Kazem Mousavizadeh
Summary: This study identified important genetic variants in patients with myeloid blast crisis chronic myeloid leukemia (CML) using integrated genomic sequencing. These variants affect genes involved in leukemia stem cell proliferation, self-renewal, and differentiation. RNA sequencing was used to confirm these variants. This approach provides insights into the pathophysiology of CML and may aid in its management.
SCIENTIFIC REPORTS
(2022)
Review
Chemistry, Multidisciplinary
Shenghan Teng, Jianrong Steve Zhou
Summary: This review summarizes the recent advances in transition metal-catalyzed asymmetric alkylation of heteroarenes using alkenes, covering literature from 2000 to late 2021. The reactions are classified into different categories based on the metal-mediated substrate activation, and the corresponding reaction mechanisms and catalyst design are discussed.
CHEMICAL SOCIETY REVIEWS
(2022)
Article
Oncology
Kiyomi Morita, Hagop M. Kantarjian, Koji Sasaki, Ghayas C. Issa, Nitin Jain, Marina Konopleva, Nicholas J. Short, Koichi Takahashi, Courtney D. DiNardo, Tapan M. Kadia, Guillermo Garcia-Manero, Naval Daver, Guillermo Montalban Bravo, Jorge E. Cortes, Farhad Ravandi, Elias Jabbour
Summary: Dasatinib monotherapy has shown modest clinical activity in CML-LBP, while combination therapy of hyper-CVAD and dasatinib has significantly improved the outcome of Ph-positive ALL. Patients with CML-LBP are less likely to achieve deep molecular remission compared to those with Ph-positive ALL, but their survival outcomes are similar. In Ph-positive ALL, achieving deeper molecular remission is associated with better survival outcomes.
Article
Biochemistry & Molecular Biology
Dan Wang, Huan Yang, Yun Zhang, Rong Hu, Dongjie Hu, Qunxian Wang, Yannan Liu, Mingjing Liu, Zijun Meng, Weihui Zhou, Weihong Song
Summary: Increased levels of CBS and H2S have been found in pediatric CML patients and cells, inhibition of CBS can reduce cell proliferation, induce apoptosis, and inhibit cell migration.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Pharmacology & Pharmacy
Hyacinthe Johnson-Ansah, Benjamin Maneglier, Francoise Huguet, Laurence Legros, Martine Escoffre-Barbe, Martine Gardembas, Pascale Cony-Makhoul, Valerie Coiteux, Laurent Sutton, Wajed Abarah, Camille Pouaty, Jean-Michel Pignon, Bachra Choufi, Sorin Visanica, Benedicte Deau, Laure Morisset, Emilie Cayssials, Mathieu Molimard, Stephane Bouchet, Francois-Xavier Mahon, Franck Nicolini, Philippe Aegerter, Jean-Michel Cayuela, Marc Delord, Heriberto Bruzzoni-Giovanelli, Philippe Rousselot
Summary: This study evaluated the value of therapeutic drug monitoring (TDM) in imatinib treatment for patients with chronic myelogenous leukemia. The results showed that TDM strategy significantly increased the plasma concentration of imatinib and improved the treatment outcome for patients.
Review
Oncology
Maiko Matsushita
Summary: Although TKIs are effective in treating CML patients, LSCs are resistant to them. Immunotherapies targeting LSCs may be crucial in curing CML.
Article
Immunology
Qingya Cui, Peiqi Liang, Haiping Dai, Wei Cui, Mengjie Cai, Zixuan Ding, Qinfen Ma, Jia Yin, Zheng Li, Sining Liu, Liqing Kang, Li Yao, Jiannong Cen, Hongjie Shen, Mingqing Zhu, Lei Yu, Depei Wu, Xiaowen Tang
Summary: Resistance to TKIs and chemotherapy in CML-BP may be overcome by CAR-T-38 cell therapy, targeting CD38 antigen, leading to significant therapeutic responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Magdalena Hinterbrandner, Viviana Rubino, Carina Stoll, Stefan Forster, Noah Schnuriger, Ramin Radpour, Gabriela M. Baerlocher, Adrian F. Ochsenbein, Carsten Riether
Summary: The study showed that leukemia stem cells (LSCs) in chronic myeloid leukemia (CML) can be killed by CD8(+) cytotoxic T cells (CTLs) in vitro, but Tregs in CML bone marrow protect LSCs from CTL-mediated elimination in vivo. TNFRSF4 was identified as a potential target to reduce the function of Tregs and enhance antileukemic immunity in CML.
Article
Hematology
Vaidehi Krishnan, Florian Schmidt, Zahid Nawaz, Prasanna Nori Venkatesh, Kian Leong Lee, Xi Ren, Zhu En Chan, Mengge Yu, Meera Makheja, Nirmala Arul Rayan, Michelle Gek Liang Lim, Alice Man Sze Cheung, Sudipto Bari, Wee Joo Chng, Hein Than, John Ouyang, Owen Rackham, Tuan Zea Tan, William Ying Khee Hwang, Charles Chuan, Shyam Prabhakar, S. Tiong Ong
Summary: Using single-cell RNA sequencing, we identified 8 significant features in the bone marrow of chronic myeloid leukemia patients that correlated with sensitivity or resistance to imatinib treatment. By employing machine learning, we accurately predicted imatinib response with over 80% accuracy, including no false positives for predicting blast crisis transformation. Patients with major molecular response exhibited a signature erythroid-specifying regulon, while those who progressed to transformation showed an inflammatory regulon.
Article
Hematology
Aram Bidikian, Elias Jabbour, Ghayas C. C. Issa, Nicholas J. J. Short, Koji Sasaki, Hagop Kantarjian
Summary: Achieving major molecular response (MMR) with BCR::ABL1 tyrosine kinase inhibitors (TKIs) is important in the treatment of chronic myeloid leukemia (CML). However, patients who achieve a major cytogenetic response (MCyR) within the first 2 years of TKI therapy can still have good long-term outcomes, even without achieving MMR. The value of MMR is less pronounced among older CML patients, who often face mortality due to comorbidities unrelated to CML.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Magdalena Ostafin, Olga Ciepiela, Michal Pruchniak, Malgorzata Wachowska, Edyta Ulinska, Piotr Mrowka, Eliza Glodkowska-Mrowka, Urszula Demkow
Summary: Patients with acute leukemia exhibit significantly impaired release of NETs by neutrophils during both the course of the disease and treatment, with full restoration of neutrophil function achieved only after successful completion of treatment. This impairment may be attributed to disease- and treatment-related factors, contributing to the deficient innate immune response and secondary immunodeficiency observed in this population.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Tomasz M. Grzywa, Agnieszka A. Koppolu, Wiktor Paskal, Klaudia Klicka, Malgorzata Rydzanicz, Jaroslaw Wejman, Rafal Ploski, Pawel K. Wlodarski
Summary: Melanoma tumors are highly heterogeneous, which leads to challenges in diagnosis and treatment failures. This study revealed significant differences in genetic mutations between high and low proliferation compartments of melanoma tumors, highlighting the functional role of genetic heterogeneity in melanoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Aniela Brodzikowska, Monika Ciechanowska, Michal Kopka, Albert Stachura, Pawel K. Wlodarski
Summary: This study aims to summarize current medical literature on dental pulp inflammation models using lipopolysaccharide (LPS). Through data gathered from 115 papers, the study presents the known effects of LPS on different cell types in dental pulp and focuses on specific receptors and particles involved in molecular pathways. This review provides an essential foundation for further research using in vitro models of pulpitis.
Article
Oncology
Joanna Drozd-Sokolowska, Krzysztof Madry, Kinga Siewiorek, Magdalena Feliksbrot-Bratosiewicz, Tomasz Stoklosa, Beata Gierej, Agnieszka Stefaniak, Malgorzata Paszkowska-Kowalewska, Jacek Sokolowski, Bartlomiej Sankowski, Grzegorz Wladyslaw Basak
Summary: The combination of azacitidine and venetoclax has been approved for treating adult treatment-naive acute myeloid leukemia patients. This treatment may also be an alternative for patients with mixed phenotype acute leukemia, for which there are no established treatment guidelines. Additionally, the incidence of tumor lysis syndrome after treatment with azacitidine and venetoclax was found to be 17%.
Article
Oncology
Marcin M. Machnicki, Anna Rzepakowska, Joanna I. Janowska, Monika Pepek, Alicja Krop, Katarzyna Pruszczyk, Piotr Stawinski, Malgorzata Rydzanicz, Jakub Grzybowski, Barbara Gornicka, Maciej Wnuk, Rafal Ploski, Ewa Osuch-Wojcikiewicz, Tomasz Stoklosa
Summary: In this study, the genomic profile of hypopharyngeal cancer was investigated using targeted next-generation sequencing. The results showed that the mutational profile of hypopharyngeal cancers might be similar to other head and neck cancers, with some minor differences, and multiple candidate actionable and prognostic genetic alterations were identified. Additionally, the study demonstrated for the first time that the KMT2C gene may function as a tumor suppressor in HNSCC.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Iga Stukan, Marek Gryzik, Grazyna Hoser, Andrew Want, Wioleta Grabowska-Pyrzewicz, Mikolaj Zdioruk, Mariola Napiorkowska, Marcin Cieslak, Karolina Krolewska-Golinska, Barbara Nawrot, Grzegorz Basak, Urszula Wojda
Summary: Chemotherapy is widely used for cancer treatment but often leads to therapy resistance. This study discovered that the novel compound BK124.1 can overcome chemotherapy resistance in chronic myeloid leukemia. BK124.1 showed efficacy in animal and cellular models, targeting multidrug resistant leukemia blasts and cancer stem cells. Future development of BK124.1 could offer a cure for chronic myeloid leukemia and other chemotherapy-resistant cancers.
Article
Biochemistry & Molecular Biology
Aleksander Salomon-Perzynski, Joanna Barankiewicz, Marcin Machnicki, Irena Misiewicz-Krzeminska, Michal Pawlak, Sylwia Radomska, Agnieszka Krzywdzinska, Aleksandra Bluszcz, Piotr Stawinski, Malgorzata Rydzanicz, Natalia Jakacka, Iwona Solarska, Katarzyna Borg, Zofia Spyra-Gorny, Tomasz Szpila, Bartosz Pula, Sebastian Grosicki, Tomasz Stoklosa, Rafal Ploski, Ewa Lech-Maranda, Jana Jakubikova, Krzysztof Jamroziak
Summary: Tracking genetic changes during multiple myeloma progression reveals different patterns of mutation evolution, with mutation loss pathway associated with better treatment response. Many druggable genes are mutated, even in heavily pre-treated patients. Redefining R-ISS at relapse is clinically valuable.
Article
Oncology
Joanna Drozd-Sokolowska, Krzysztof Madry, Joanna Barankiewicz, Katarzyna Kobylinska, Przemyslaw Biecek, Jagoda Rytel, Ewa Karakulska-Prystupiuk, Kamila Skwierawska, Aleksander Salomon-Perzynski, Tomasz Stoklosa, Grzegorz Wladyslaw Basak
Summary: COVID-19 is a frequent complication of AZA-VEN treatment during the COVID-19 pandemic, leading to death in a significant proportion of patients.
Review
Oncology
Klaudia Klicka, Tomasz M. Grzywa, Aleksandra Mielniczuk, Alicja Klinke, Pawel K. Wlodarski
Summary: miR-200 family is a dysregulated miRNA family in cancer that has the potential to be used as diagnostic and prognostic biomarkers. They regulate various features of cancer and their levels correlate with clinical parameters such as patients' survival.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Wioleta Dudka, Grazyna Hoser, Shamba S. S. Mondal, Laura Turos-Korgul, Julian Swatler, Monika Kusio-Kobialka, Magdalena Wolczyk, Agata Klejman, Marta Brewinska-Olchowik, Agata Kominek, Milena Wiech, Marcin M. M. Machnicki, Ilona Seferynska, Tomasz Stoklosa, Katarzyna Piwocka
Summary: This study reveals that ISR inhibition combined with imatinib treatment can effectively eliminate TKI-resistant leukemia cells. The combined treatment inhibits the STAT5 and RAS/RAF/MEK/ERK pathways, reducing cell resistance.
Article
Cell Biology
Lewandowski Krzysztof, Kopydlowska Agata, Kandula Zuzanna, Bartlomiej Sankowski, Marcin Machnicki, Baranska Marta, Gwozdz-Bak Kinga, Kubicki Tadeusz, Plotka Anna, Przysiecka Lucja, Dworacki Grzegorz, Kozlowski Piotr, Stoklosa Tomasz
Summary: 3%-14% of BCR-ABL negative MPNPh- patients have concurrent MGUS. A 50-year-old patient with type 2 CALR Lys385Asnfs*47 mutation positive essential thrombocythemia (ET) developed symptomatic multiple myeloma (MM) 13 years after ET diagnosis during PEG-INF2 alpha treatment. The origin of MM cells in MPNPh- patients remains unknown, but research suggests that mutant CALR protein may impact the function and genomic stability of myeloid cells.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2023)
Article
Oncology
Anna Deregowska, Monika Pepek, Iwona Solarska, Marcin M. Machnicki, Katarzyna Pruszczyk, Marek Dudzinski, Joanna Niesiobedzka-Krezel, Ilona Seferynska, Waldemar Sawicki, Maciej Wnuk, Tomasz Stoklosa
Summary: In this study, the telomeric complex expression and function in the molecular pathogenesis of CML were analyzed. It was found that the telomere length in CD34+ CML cells shortened during the progression of the disease, which was correlated with the expression level of BCR::ABL1 transcript but not with telomerase activity. The increased expression of BCR::ABL1 was positively correlated with the expression of TRF2, RAP1, TPP1, DKC1, TNKS1, and TNKS2 genes. These findings provide insight into the mechanisms responsible for the genomic instability of leukemic cells and CML progression.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Toxicology
Anna Deregowska, Anna Lewinska, Aleksandra Warzybok, Tomasz Stoklosa, Maciej Wnuk
Summary: This study demonstrates that in imatinib-resistant CML cells, there is a decrease in telomere length, lower protein levels of TRF2 and RAP1, and increased expression of TERRA. Additionally, enhanced activity of the glycolytic pathway is observed in these cells. A negative correlation between telomere length and advanced glycation end products (AGE) is also revealed in CD34+ cells from CML patients. Overall, affected expression of shelterin complex proteins, TERRA levels, and glucose consumption rate may contribute to telomere dysfunction in imatinib-resistant CML cells.
TOXICOLOGY IN VITRO
(2023)
Article
Reproductive Biology
Izabela Walasik, Klaudia Klicka, Tomasz M. Grzywa, Iwona Szymusik, Miros law Wielgos, Bronis lawa Pietrzak, Artur Ludwin, Pawel Wlodarski
Summary: This study evaluated the potential of circulating miRNAs as biomarkers for endometriosis. The results showed that miR-451a and miR-3613-5p were significantly decreased in the plasma of endometriosis patients, while miR-125b-5p and miR-199a-3p did not differ between groups. Therefore, miR-3613-5p may be a better biomarker for endometriosis.
REPRODUCTIVE BIOLOGY
(2023)
Article
Pathology
Kinga Szczepaniak, Wiktor Paskal, Zofia Kusmierczyk, Jaroslaw Wejman, Joanna Ostrowska, Wieslaw Tarnowski, Pawel Wlodarski
Summary: Alterations of PD1/PD-L1 pathway may lead to an excessive inflammatory response in the intestinal wall in inflammatory bowel diseases (IBD). The expression of PD-1 and PD-L1 in different compartments of the intestinal wall is heterogeneous and may depend on individual characteristics.
POLISH JOURNAL OF PATHOLOGY
(2022)
