Article
Oncology
Yanbo Nie, Liang Shao, Hong Zhang, Colin K. He, Hongyu Li, Junyan Zou, Long Chen, Huaiyue Ji, Hao Tan, Yani Lin, Kun Ru
Summary: CMML patients in China exhibit a unique mutational spectrum, with common mutations in epigenetic modifiers (TET2 and ASXL1), signaling transduction pathway components (NRAS), and splicing factor (SRSF2). DNMT3A, ETV6, FLT3, and NPM1 mutations are associated with progression to sAML. ASXL1 mutation and treatment modalities are independent prognostic factors for CMML.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2022)
Article
Oncology
Emmanuella Oyogoa, Lukas Streich, Philipp W. Raess, Theodore Braun
Summary: This is a case report on a 27-year-old female with chronic myeloid leukemia (CML) who developed kinase-independent resistance and disease progression. The patient initially had chronic phase (CP) CML and acquired mutations in ASXL1 and RUNX1. Due to uncontrolled disease, she progressed to a chronic myelomonocytic leukemia-like (CMML) accelerated phase (AP) disease and obtained an IDH1 mutation. The disease progression was associated with the development of an inflammatory serositis, a phenomenon not typically observed in AP-CML.
FRONTIERS IN ONCOLOGY
(2023)
Review
Oncology
Onyee Chan, Aline Renneville, Eric Padron
Summary: CMML is a rare, heterogeneous myeloid malignancy with challenging diagnosis and a need for more molecular information. Symptom-directed approaches form the basis of management, including pharmacological treatment and transplantation. Early clinical trial results show promise for novel therapies in treating CMML.
Article
Oncology
Gregor Eisenwort, Irina Sadovnik, Alexandra Keller, Daniel Ivanov, Barbara Peter, Daniela Berger, Gabriele Stefanzl, Karin Bauer, Katharina Slavnitsch, Georg Greiner, Karoline V. Gleixner, Wolfgang R. Sperr, Michael Willmann, Heinz Sill, Peter Bettelheim, Klaus Geissler, Michael Deininger, Thomas Rulicke, Peter Valent
Summary: Chronic myelomonocytic leukemia (CMML) is a stem cell-derived neoplasm characterized by dysplasia and uncontrolled expansion of monocytes. Leukemic stem cells (LSC) in CMML are found to reside in a CD34(+)/CD38(-) fraction and express a distinct profile of surface markers. During progression to secondary acute myeloid leukemia (sAML), LSC acquire or upregulate certain cytokine receptors.
Article
Oncology
Douglas Tremblay, Noa Rippel, Jonathan Feld, Siraj M. El Jamal, John Mascarenhas
Summary: Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy characterized by monocytosis, dysplasia, and proliferative features. Treatment strategies range from observation to stem cell transplantation, with therapies including hydroxyurea and hypomethylating agents. The recently approved oral decitabine/cedazuridine offers a convenient treatment option. Further research is needed to identify unique targets for CMML therapeutics.
Article
Multidisciplinary Sciences
Daniel S. Park, Son C. Nguyen, Randi Isenhart, Parisha P. Shah, Wonho Kim, R. Jordan Barnett, Aditi Chandra, Jennifer M. Luppino, Jailynn Harke, May Wai, Patrick J. Walsh, Richard J. Abdill, Rachel Yang, Yemin Lan, Sora Yoon, Rebecca Yunker, Masato T. Kanemaki, Golnaz Vahedi, Jennifer E. Phillips-Cremins, Rajan Jain, Eric F. Joyce
Summary: Researchers developed a high-throughput DNA or RNA labeling technology called HiDRO, enabling the quantitative measurement of chromatin interactions in single cells. By screening the human druggable genome, they identified over 300 factors that influence genome folding during interphase, with 43 genes validated to increase or decrease interactions between topologically associating domains. Inhibition of the kinase GSK3A was found to increase long-range chromatin looping interactions in a genome-wide and cohesin-dependent manner. These findings highlight the importance of GSK3A signaling in nuclear architecture and demonstrate the utility of HiDRO for identifying mechanisms of spatial genome organization.
Article
Hematology
Wenmin Han, Feng Zhou, Zheng Wang, Haiying Hua, Wei Qin, Zhuxia Jia, Xiaohui Cai, Meiyu Chen, Jie Liu, Hongying Chao, Xuzhang Lu
Summary: The study evaluated the mutational landscape of CMML and found that patients aged 60 years and older were more likely to have mutations such as TET2 and ASXL1. Different mutations were associated with patients' overall survival and AML-free survival.
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2022)
Letter
Dermatology
Roberto Maglie, Stefano Senatore, Gioia Di Stefano, Marta Barzacchi, Vincenza Maio, Francesca Montefusco, Maria Efenesia Baffa, Beatrice Bianchi, Marco Santucci, Emiliano Antiga
Summary: We describe an unusual case of myelodysplasia cutis in a patient with chronic myelomonocytic leukaemia.
CLINICAL AND EXPERIMENTAL DERMATOLOGY
(2022)
Article
Oncology
Johannes Lorenz Berg, Bianca Perfler, Stefan Hatzl, Marie-Christina Mayer, Sonja Wurm, Barbara Uhl, Andreas Reinisch, Ingeborg Klymiuk, Sascha Tierling, Gudrun Pregartner, Gerhard Bachmaier, Andrea Berghold, Klaus Geissler, Martin Pichler, Gerald Hoefler, Herbert Strobl, Albert Woelfler, Heinz Sill, Armin Zebisch
Summary: The study identified decreased expression of miR-125a in CMML and highlighted its significance as a mediator of HMA efficacy in this malignancy.
CLINICAL EPIGENETICS
(2021)
Article
Hematology
Mrinal M. Patnaik, Ayalew Tefferi
Summary: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms. Diagnosis is based on the presence of peripheral blood monocytosis and bone marrow dysplasia. Mutations and risk factors affect prognosis, and hypomethylating agents are commonly used for treatment. Allogeneic stem cell transplant is a potential curative option.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Computer Science, Information Systems
Takuya Fujihashi, Toshiaki Koike-Akino, Philip Orlik, Takashi Watanabe
Summary: Screen-camera communications using LCD screen and camera can achieve high transmission rates, with methods like nonlinear channel equalization and nonbinary channel coding found to be effective in improving performance. Experimental results show that our proposed scheme outperforms existing schemes in terms of transmission rates.
IEEE TRANSACTIONS ON MOBILE COMPUTING
(2021)
Article
Oncology
Liya Ma, Lingxu Jiang, Wenli Yang, Yingwan Luo, Chen Mei, Xinping Zhou, Gaixiang Xu, Weilai Xu, Li Ye, Yanlin Ren, Chenxi Lu, Peipei Lin, Jie Jin, Hongyan Tong
Summary: The study of chronic myelomonocytic leukemia (CMML) patients in China showed that a majority of patients were classified as intermediate-2 or high risk according to specific prognostic scoring system. Patients receiving hypomethylating agents (HMAs) treatment had higher overall response rate, with the HMAs monotherapy group showing prolonged overall survival compared to chemotherapy. Further research is needed to develop novel therapeutics for better outcomes.
Article
Multidisciplinary Sciences
Shaochen You, Michael J. Bollong
Summary: ChREBP, a central regulator of metabolism, senses and responds to dietary glucose levels by stimulating the transcription of glycolytic and lipogenic enzymes. A recent pharmacological screen identified novel inhibitors of ChREBP-driven transcription, providing a toolkit to investigate ChREBP activation and potential therapeutic approaches for metabolic diseases.
Article
Biochemistry & Molecular Biology
Maria Teresa Bochicchio, Giorgia Micucci, Silvia Asioli, Martina Ghetti, Giorgia Simonetti, Alessandro Lucchesi
Summary: Chronic myelomonocytic leukemia (CMML) is a hematological neoplasm characterized by monocytosis, splenomegaly, thrombocytopenia, and anemia. This study presented a case of CMML-2 with TET2, SRSF2, and a rare CSF3R germline mutation. The patient achieved normalization of the hemostatic process after treatment with Azacitidine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Alexandra Rezazadeh, Michael Deininger, Ehab Atallah
Summary: Chronic myelomonocytic leukemia (CMML) is a clonal hematologic malignancy with myelodysplastic and myeloproliferative features, affecting older individuals. Current treatments, such as hypomethylating agents and stem cell transplant, have limited efficacy. Recent research has identified key molecular pathways involved in disease progression, including inflammation. However, this knowledge has not yet translated into improved outcomes, suggesting the need for new approaches.
CURRENT TREATMENT OPTIONS IN ONCOLOGY
(2023)
Letter
Oncology
Ellin Berman, Brian J. Druker, Richard Burwick
JOURNAL OF CLINICAL ONCOLOGY
(2019)
Article
Oncology
Leylah M. Drusbosky, Robinson Vidva, Saji Gera, Anjanasree Lakshminarayana, Vijayashree P. Shyamasundar, Ashish Kumar Agrawal, Anay Talawdekar, Taher Abbasi, Shireen Vali, Cristina E. Tognon, Stephen E. Kurtz, Jeffrey W. Tyner, Shannon K. McWeeney, Brian J. Druker, Christopher R. Cogle
Article
Hematology
Sunil K. Joshi, Kristin Qian, William H. Bisson, Kevin Watanabe-Smith, Ariane Huang, Daniel Bottomly, Elie Traer, Jeffrey W. Tyner, Shannon K. McWeeney, Monika A. Davare, Brian J. Druker, Cristina E. Tognon
Article
Oncology
Christopher A. Eide, Stephen E. Kurtz, Andy Kaempf, Nicola Long, Anupriya Agarwal, Cristina E. Tognon, Motomi Mori, Brian J. Druker, Bill H. Chang, Alexey V. Danilov, Jeffrey W. Tyner
Review
Oncology
Theodore P. Braun, Christopher A. Eide, Brian J. Druker
Article
Oncology
Sunil K. Joshi, Jamie M. Keck, Christopher A. Eide, Daniel Bottomly, Elie Traer, Jeffrey W. Tyner, Shannon K. McWeeney, Cristina E. Tognon, Brian J. Druker
Article
Hematology
Alisa Damnernsawad, Daniel Bottomly, Stephen E. Kurtz, Christopher A. Eide, Shannon K. McWeeney, Jeffrey W. Tyner, Tamilla Nechiporuk
Summary: Drug resistance in acute myeloid leukemia (AML) poses challenges to targeted therapies. This study identified LZTR1, NF1, TSC1, and TSC2 as mediators of resistance to sorafenib, a FLT3 inhibitor, through a genome-wide CRISPR screen. The combination of FLT3 and MEK inhibitors showed enhanced efficacy in AML patients with FLT3 mutations and resistance to FLT3 inhibitors.
Article
Oncology
Renata Scopim-Ribeiro, Joao Agostinho Machado-Neto, Christopher A. Eide, Juan Luiz Coelho-Silva, Bruna Alves Fenerich, Jaqueline Cristina Fernandes, Priscila Santos Scheucher, Samantha L. Savage Stevens, Paula de Melo Campos, Sara T. Olalla Saad, Leonardo de Carvalho Palma, Lorena Lobo de Figueiredo-Pontes, Belinda Pinto Simoes, Eduardo Magalhaes Rego, Cristina E. Tognon, Brian J. Druker, Fabiola Traina
Summary: NT157 demonstrates antineoplastic effects on CML cells by inhibiting multiple signaling pathways associated with BCR-ABL1, inducing apoptosis, and significantly affecting cell proliferation, survival, and colony formation.
INVESTIGATIONAL NEW DRUGS
(2021)
Article
Oncology
Paul Yenerall, Rahul K. Kollipara, Kimberley Avila, Michael Peyton, Christopher A. Eide, Daniel Bottomly, Shannon K. McWeeney, Yan Liu, Kenneth D. Westover, Brian J. Druker, John D. Minna, Ralf Kittler
Summary: LentiMutate technology efficiently identifies drug resistance mutations in drug targets by leveraging the error-prone nature of HIV-1 reverse transcriptase. This technique, validated with clinically relevant EGFR resistance mutations, has been successfully applied to multiple clinical anticancer drugs, uncovering novel resistance mutations in imatinib and AMG 510.
Article
Oncology
Tingting Liu, Vi Lam, Elana Thieme, Duanchen Sun, Xiaoguang Wang, Fei Xu, Lili Wang, Olga V. Danilova, Zheng Xia, Jeffrey W. Tyner, Stephen E. Kurtz, Alexey V. Danilov
Summary: AZD5991 targets Mcl-1 effectively in lymphoid malignancies and overcomes resistance. Inhibition of Mcl-1 results in mitochondrial dysfunction, with TP53 and oxidative phosphorylation playing crucial roles in resistance to Mcl-1 inhibition.
CLINICAL CANCER RESEARCH
(2021)
Article
Hematology
Stephen E. Kurtz, Christopher A. Eide, Andy Kaempf, Nicola Long, Daniel Bottomly, Olga Nikolova, Brian J. Druker, Shannon K. McWeeney, Bill H. Chang, Jeffrey W. Tyner, Anupriya Agarwal
Summary: Using ex vivo drug screening, a combination of p38 MAPK inhibitor doramapimod and BCL2 inhibitor venetoclax showed enhanced efficacy compared to single agents in acute myeloid leukemia (AML) patient samples, while sparing primary stromal cells. Sensitivity to each agent was associated with different tumor cell differentiation states, but the combination mitigated resistance and enhanced efficacy. The mechanism behind the enhanced efficacy may involve inhibition of p38 MAPK-mediated phosphorylation of BCL2. These findings suggest a potential strategy for treating AML by targeting both p38 MAPK and BCL2.
Review
Oncology
Jeffrey W. Tyner, Franziska Haderk, Anbarasu Kumaraswamy, Linda B. Baughn, Brian Van Ness, Song Liu, Himangi Marathe, Joshi J. Alumkal, Trever G. Bivona, Keith Syson Chan, Brian J. Druker, Alan D. Hutson, Peter S. Nelson, Charles L. Sawyers, Christopher D. Willey
Summary: The diversity of cancer and the problem of drug resistance present major challenges in cancer treatment, but understanding the types and biological causes of resistance can provide opportunities for personalized therapies.
Article
Oncology
Kyle A. Romine, Tamilla Nechiporuk, Daniel Bottomly, Sophia Jeng, Shannon K. McWeeney, Andy Kaempf, M. Ryan Corces, Ravindra Majeti, Jeffrey W. Tyner
Summary: The study identified monocytic differentiation regulators and AHR signaling as primary determinants of response to BET inhibitors (BETi). Screens identified BCL2 and CDK6 as druggable vulnerabilities for rescuing BETi sensitivity. Combination of BETi with venetoclax significantly enhanced sensitivity in monocytic AML patient samples refractory to venetoclax in vitro.
BLOOD CANCER DISCOVERY
(2021)
Article
Biochemistry & Molecular Biology
Bruna Alves Fenerich, Jaqueline Cristina Fernandes, Ana Paula Nunes Rodrigues Alves, Juan Luiz Coelho-Silva, Renata Scopim-Ribeiro, Priscila Santos Scheucher, Christopher A. Eide, Cristina E. Tognon, Brian J. Druker, Eduardo Magalhaes Rego, Joao Agostinho Machado-Neto, Fabiola Traina
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2020)
Article
Oncology
Haijiao Zhang, Yusuke Nakauchi, Thomas Kohnke, Melissa Stafford, Daniel Bottomly, Rozario Thomas, Beth Wilmot, Shannon K. McWeeney, Ravindra Majeti, Jeffrey W. Tyner
