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.
Article
Biochemistry & Molecular Biology
Raquel Alves, Ana Cristina Goncalves, Joana Jorge, Antonio M. Almeida, Ana Bela Sarmento-Ribeiro
Summary: This study evaluated the therapeutic potential of elacridar, a P-glycoprotein and BCRP inhibitor, in CML cell lines. The results showed that elacridar as monotherapy was not effective, but when combined with imatinib, it could overcome resistance. This provides a new treatment option for overcoming TKI resistance.
Article
Medicine, General & Internal
Esraa K. Al-Amleh, Ola M. Al-Sanabra, Khalid M. Alqaisi, Moath Alqaraleh, Jumana Al-Nahal, Lama Hamadneh, Mohammed Imad Malki, Jehad F. Alhmoud
Summary: This study compared the effects of single and combined treatment of IM and HU on hematological parameters and gene expression in CML patients. The findings suggest that the combined therapy is more effective in raising lymphocyte count and reducing the proportion of neutrophils compared to single medicines.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Oncology
Federica Maggi, Maria Beatrice Morelli, Daniele Tomassoni, Oliviero Marinelli, Cristina Aguzzi, Laura Zeppa, Massimo Nabissi, Giorgio Santoni, Consuelo Amantini
Summary: This study found that cannabidiol (CBD) inhibits cell proliferation and cell cycle in chronic myeloid leukemia (CML) cells through the activation of transient receptor potential vanilloid 2 (TRPV2). CBD also promotes mitochondrial dysfunction and mitophagy, and affects cellular differentiation markers. Additionally, a synergistic effect was observed when CBD was combined with the standard drug imatinib, and CBD still had an effect on imatinib-resistant cells.
Article
Oncology
Frederic Millot, Meinolf Suttorp, Stephanie Ragot, Guy Leverger, Jean-Hugues Dalle, Caroline Thomas, Nathalie Cheikh, Brigitte Nelken, Marilyne Poiree, Genevieve Plat, Birgitta Versluys, Birgitte Lausen, Marina Borisevich
Summary: The study evaluated the rate of children with childhood chronic myeloid leukemia who remained in molecular response after discontinuing imatinib following sustained deep molecular response (DMR). The findings showed fluctuating molecular free remission rates at different time points post-discontinuation, with no significant influencing factors identified.
Article
Biochemistry & Molecular Biology
Sylwester Glowacki, Ewelina Synowiec, Marzena Szwed, Monika Toma, Tomasz Skorski, Tomasz Sliwinski
Summary: Chronic myeloid leukemia (CML) is caused by the BCR-ABL1 protein, inducing oxidative stress and leading to resistance to imatinib (IM). Research shows increased ROS accumulation in BCR-ABL1 positive cells, heightened DNA damage in IM-sensitive cells, and alterations in antioxidant enzyme activity and mitochondrial potential in IM-resistant cells.
Article
Infectious Diseases
Shashi B. L. Bhushan, Sunil Wanve, Parshottam Koradia, Vinay Bhomia, Pravin Soni, Sisir Chakraborty, Akash Khobragade, Shashank Joshi, Sanjeev Kumar Mendiratta, Kevin Kumar Kansagra, Anurag Parihar, Sunil Sharma, Jatin Patel
Summary: The study showed that PEG IFN-alpha 2b administered with standard of care can improve the clinical status of patients with moderate COVID-19, promote early viral clearance, decrease the duration of supplemental oxygen, and has the potential as a viable treatment option to limit the spread of SARS-CoV-2.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Cell Biology
Narissa Parry, Caroline Busch, Victoria Assmann, Jennifer Cassels, Alan Hair, G. Vignir Helgason, Helen Wheadon, Mhairi Copland
Summary: Dysregulation of the BCL-2 family is implicated in protecting CML cells, making it a viable therapeutic target. BH3 mimetics show clinical promise in the treatment of CML and can be used in combination with standard therapies. Combination of TKIs and BH3 mimetics significantly reduces cell viability and induces apoptosis in BP-CML cells. BH3 mimetics are more effective in myeloid BP-CML compared to single treatment.
CELL DEATH DISCOVERY
(2022)
Article
Hematology
Fadi G. Haddad, Koji Sasaki, Ghayas C. Issa, Guillermo Garcia-Manero, Farhad Ravandi, Tapan Kadia, Jorge Cortes, Marina Konopleva, Naveen Pemmaraju, Yesid Alvarado, Musa Yilmaz, Gautam Borthakur, Courtney DiNardo, Nitin Jain, Naval Daver, Nicholas J. Short, Elias Jabbour, Hagop Kantarjian
Summary: This study evaluated the outcome of TKI discontinuation in CML patients and identified factors associated with success rates of treatment-free remission (TFR). The study found that TFR is safe and feasible in patients with Ph-positive CML on TKI therapy. Achieving MR4 or MR4.5 for at least 5 years was correlated with a better outcome.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rachid Lahlil, Anne Aries, Maurice Scrofani, Celine Zanetti, Desline Hennequin, Bernard Drenou
Summary: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease characterized by the presence of the BCR-ABL fusion gene. Treatment with tyrosine kinase inhibitors (TKIs) such as imatinib mesylate (IM) has significantly improved clinical outcomes for CML patients, but IM resistance remains a major challenge. The cause of IM resistance in CML cells is unclear, but additional genetic alterations in leukemic stem cells (LSCs) are a common cause of relapse. A study found that a rare subpopulation of stem cells called very small embryonic-like stem cells (VSELs) in adult CML patients is resistant to IM and less sensitive to apoptosis compared to leukemic hematopoietic stem cells (HSCs). The expression levels of certain miRNAs are also affected in these IM-resistant VSELs, including miR-126 and miR-21, which are involved in LSC leukemia-initiating capacity and growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Giordana Feriotto, Paolo Marchetti, Riccardo Rondanin, Federico Tagliati, Serena Aguzzi, Simone Beninati, Fabio Casciano, Claudio Tabolacci, Carlo Mischiati
Summary: In this study, the bis-ketone moiety of curcumin (CUR) was replaced to obtain more stable derivatives 2 and 22. The evaluation of their chemical-physical characteristics and cell experiments showed that derivatives 2 and 22 had better bioavailability and stability than CUR, and exhibited significant cytotoxicity and pro-apoptotic effects on chronic myeloid leukemia (CML) cells. Moreover, derivative 22 was able to reverse drug resistance in CML cells resistant to imatinib (IM).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Medicine, General & Internal
Ik-Chan Song, Sang-Noon Yeon, Myeong-Won Lee, Hyewon Ryu, Hyo-Jin Lee, Hwan-Jung Yun, Byung Joo Sun, Jae-Hyeong Park, Jin-Ok Jeong, Deog-Yeon Jo
Summary: This study retrospectively analyzed the prevalence of pulmonary hypertension (PH) among Korean chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs), such as dasatinib, imatinib, and nilotinib. The results showed that not only dasatinib, but also imatinib and nilotinib could induce PH in CML patients. Risk factors for developing PH included age over 60, dasatinib treatment, and positive cardiopulmonary symptoms/signs at the time of transthoracic echocardiography.
Article
Oncology
Fang Cheng, Guolin Yuan, Qiang Li, Zheng Cui, Weiming Li
Summary: This study confirmed the long-term efficacy and safety of imatinib for treating Chinese CML patients. Additionally, it demonstrated the feasibility of imatinib dose reduction and treatment-free remission attempts in patients with sustained stable deep molecular response after years of imatinib treatment in real-life settings.
FRONTIERS IN ONCOLOGY
(2023)
Editorial Material
Oncology
Eda Nuhoglu Kantarci, Ece Tolgay, Ahmet Emre Eskazan
Summary: This editorial discusses the search for the best patient-based treatment option as well as evaluates a recent study by Tiribelli et al., published in Cancer.
Article
Oncology
Arnon Nagler, Jacques-Emmanuel Galimard, Myriam Labopin, Didier Blaise, William Arcese, Silvia Maria Trisolini, Depei Wu, Arnaud Pigneux, Gwendolyn Van Gorkom, Marie-Therese Rubio, Tobias Gedde-Dahl, Anne Huynh, Francesco Lanza, Norbert-Claude Gorin, Mohamad Mohty
Summary: AML patients who required two chemotherapy courses to achieve complete remission had inferior leukemia free survival and overall survival rates, as well as higher relapse incidence. Allogeneic transplantation may be a better option for these patients to improve outcomes.
Article
Hematology
Tania Brandstoetter, Johannes Schmoellerl, Reinhard Grausenburger, Sebastian Kollmann, Eszter Doma, Jani Huuhtanen, Thorsten Klampfl, Thomas Eder, Florian Grebien, Gregor Hoermann, Johannes Zuber, Satu Mustjoki, Barbara Maurer, Veronika Sexl
Summary: Gain-of-function mutations in the STAT3 gene are frequently found in patients with LGLL, NK/T-cell leukemia, and adult T-cell leukemia/lymphoma. Murine hematopoietic stem and progenitor cell models expressing mutated STAT3Y640F showed increased proliferation and self-renewal potential. Through gene expression analysis and chromatin occupancy profiling, a conserved set of direct transcriptional targets of STAT3Y640F, including SBNO2, was identified. The STAT3-SBNO2 axis is also present in other STAT3-driven hematopoietic malignancies, suggesting SBNO2 as a potential therapeutic target.
Article
Hematology
Heikki Kuusanmaki, Sari Kytola, Ida Vanttinen, Tanja Ruokoranta, Amanda Ranta, Jani Huuhtanen, Minna Suvela, Alun Parsons, Annasofia Holopainen, Anu Partanen, Milla E. L. Kuusisto, Sirpa Koskela, Riikka Raty, Maija Itala-Remes, Imre Vastrik, Olli Dufva, Sanna Siitonen, Kimmo Porkka, Krister Wennerberg, Caroline A. Heckman, Pia Ettala, Marja Pyorala, Johanna Rimpilainen, Timo Siitonen, Mika Kontro
Summary: The BCL-2 inhibitor venetoclax has revolutionized the treatment of acute myeloid leukemia (AML) in patients not benefiting from intensive chemotherapy. However, treatment failure remains a challenge, and predictive markers are needed, particularly for relapsed or refractory AML. Ex vivo drug sensitivity testing may correlate with outcomes, but its prospective predictive value remains unexplored.
Article
Multidisciplinary Sciences
Benedicte Sjo Tislevoll, Monica Hellesoy, Oda Helen Eck Fagerholt, Stein-Erik Gullaksen, Aashish Srivastava, Even Birkeland, Dimitrios Kleftogiannis, Pilar Ayuda-Duran, Laure Piechaczyk, Dagim Shiferaw Tadele, Jorn Skavland, Baliakas Panagiotis, Randi Hovland, Vibeke Andresen, Ole Morten Seternes, Tor Henrik Anderson Tvedt, Nima Aghaeepour, Sonia Gavasso, Kimmo Porkka, Inge Jonassen, Yngvar Floisand, Jorrit Enserink, Nello Blaser, Bjorn Tore Gjertsen
Summary: In this study, the initial signaling response to standard induction chemotherapy in 32 acute myeloid leukemia (AML) patients was investigated using 36-dimensional mass cytometry. The reduction of extracellular-signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK) phosphorylation in the myeloid cell compartment 24 h post-chemotherapy was found to be a significant predictor of patient 5-year overall survival in this cohort. This study demonstrates the value of mass cytometry in early response evaluation in AML and highlights the potential of functional signaling analyses in precision oncology diagnostics.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Inge G. P. Geelen, Stein-Erik Gullaksen, Mette M. Ilander, Ulla Olssen-Stromberg, Satu Mustjoki, Johan Richter, Nicole M. A. Blijlevens, Willem M. Smit, Bjorn T. Gjertsen, Tobias Gedde-Dahl, Berit Markevarn, Malika M. A. Koppes, Peter E. Westerweel, Henrik Hjorth-Hansen, Jeroen J. W. M. Janssen
Summary: To improve molecular response in chronic phase chronic myeloid leukemia (CML) patients who had not achieved at least a molecular response BCR-ABL1(IS) (MR4.0) after at least 2 years of imatinib therapy, a prospective evaluation was conducted to determine if they could achieve MR4.0 after switching to a combination of nilotinib and 9 months of pegylated interferon-alpha 2b (PegIFN). The primary endpoint of confirmed MR4.0 at month 12 was reached by 44% of patients, with 81% of patients achieving an unconfirmed MR4.0. However, premature discontinuations were common due to mood disturbances after the introduction of PegIFN, raising concerns about the feasibility of the combination therapy for this patient population and treatment goal. A comprehensive clinical substudy program was implemented to assess the impact on the immunological profile.
ANNALS OF HEMATOLOGY
(2023)
Letter
Hematology
Lok Lam Ngai, Diana Hanekamp, Fleur Janssen, Jannemieke Carbaat-Ham, Maaike A. M. A. Hofland, Mona M. H. E. Fayed, Angele Kelder, Laura Oudshoorn-van Marsbergen, Willemijn J. Scholten, Alexander N. Snel, Costa Bachas, Jesse M. Tettero, Dimitri A. Breems, Thomas Fischer, Bjorn T. Gjertsen, Laimonas Griskevicius, Gunnar Juliusson, Arjan A. van de Loosdrecht, Johan A. Maertens, Markus G. Manz, Thomas Pabst, Jakob R. Passweg, Kimmo Porkka, Peter J. M. Valk, Patrycja Gradowska, Bob Lowenberg, David C. de Leeuw, Jeroen J. W. M. Janssen, Gert J. Ossenkoppele, Jacqueline Cloos
Article
Biophysics
Arnon Nagler, Myriam Labopin, Stephan Mielke, Jakob Passweg, Didier Blaise, Tobias Gedde-Dahl, Jan J. J. Cornelissen, Urpu Salmenniemi, Ibrahim Yakoub-Agha, Peter Remenyi, Gerard Socie, Gwendolyn van Gorkom, Helene Labussiere-Wallet, Xiao-Jun Huang, Marie Therese Rubio, Jenny Byrne, Charles Craddock, Laimonas Griskevicius, Fabio Ciceri, Mohamad Mohty
Summary: This study compared the outcomes of hematopoietic stem cell transplants in acute myeloid leukemia patients in first complete remission from different donor sources. The results showed that acute graft-versus-host disease (GVHD) was more common in all non-sibling donor groups. Chronic GVHD rates were also higher in certain unrelated donor groups. However, overall survival and leukemia-free survival did not differ significantly between donor types.
BONE MARROW TRANSPLANTATION
(2023)
Article
Oncology
Rama Al Hamed, Maud Ngoya, Jacques-Emmanuel Galimard, Henrik Sengeloev, Tobias Gedde-Dahl, Aleksandr Kulagin, Uwe Platzbecker, Ibrahim Yakoub-Agha, Jenny L. Byrne, Thomas Valerius, Gerard Socie, Nicolaus Kroeger, Didier Blaise, Ali Bazarbachi, Jaime Sanz, Fabio Ciceri, Arnon Nagler, Mohamad Mohty
Summary: This retrospective study investigates the impact of time on allogeneic hematopoietic cell transplantation (allo-HCT) outcomes for patients with acute myeloid leukemia (AML) in second complete remission (CR2). The results show that outcomes of allo-HCT in CR2 have significantly improved over time, with the most favorable outcomes achieved with a matched sibling donor (MSD).
Meeting Abstract
Oncology
M. Kjellander Kynning, Y. Nannya, G. Todisco, T. Yoshizato, B. Tesi, T. Mortera-Blanco, A. -C. Bjorklund, O. Bruck, K. Ohyashiki, T. Ishikawa, Y. Ochi, T. Haferlach, S. Mustjoki, E. Hellstrom-Lindberg, S. Ogawa, J. Ungerstedt
Article
Genetics & Heredity
Deborah F. Nacer, Johan Vallon-Christersson, Nicklas Nordborg, Hans Ehrencrona, Anders Kvist, Ake Borg, Johan Staaf
Summary: The study found that breast tumors in patients screened for PGVs showed more aggressive characteristics, especially in the case of triple-negative breast cancer (TNBC). However, the ability to improve screening accuracy using current patient and tumor characteristics remains questionable and further research is needed.
Article
Oncology
Anna Ofverholm, Therese Toerngren, Anna Rosen, Brita Arver, Zakaria Einbeigi, Karin Haraldsson, Anne Kinhult Stahlbom, Ekaterina Kuchinskaya, Annika Lindblom, Beatrice Melin, Ylva Paulsson-Karlsson, Marie Stenmark-Askmalm, Emma Tham, Anna von Wachenfeldt, Anders Kvist, Ake Borg, Hans Ehrencrona
Summary: This study assessed the genetic variation in a large cohort of women with suspected HBOC and found that extending clinical genetic screening from BRCA1 and BRCA2 to 13 established cancer predisposition genes almost doubles the diagnostic yield. This has implications for genetic counseling and clinical guidelines.
Editorial Material
Biochemistry & Molecular Biology
Anna Rosen, Mateja Krajc, Hans Ehrencrona, Svetlana Bajalica-Lagercrantz
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Oncology
Johanna Vikkula, Kristiina Uusi-Rauva, Tuuli Ranki, Iiro Toppila, Maria Aalto-Setala, Katariina Pousar, Lotta Vassilev, Kimmo Porkka, Raija Silvennoinen, Oscar Bruck
Summary: This study analyzed data from 509 adult MM patients and found that treatment pattern diversity increased with improved access to novel treatments. For patients eligible for stem cell transplantation, high first-year hospitalization costs were followed by stable resource requirements.
Article
Oncology
Eirini Giannakopoulou, Madeleine Lehander, Stina Virding Culleton, Weiwen Yang, Yingqian Li, Terhi Karpanen, Tetsuichi Yoshizato, Even H. Rustad, Morten Milek Nielsen, Ravi Chand Bollineni, Trung T. Tran, Marina Delic-Sarac, Thea Johanne Gjerdingen, Karolos Douvlataniotis, Maarja Laos, Muhammad Ali, Amy Hillen, Stefania Mazzi, Desmond Wai Loon Chin, Adi Mehta, Jeppe Sejero Holm, Amalie Kai Bentzen, Marie Bill, Marieke Griffioen, Tobias Gedde-Dahl, Soren Lehmann, Sten Eirik W. Jacobsen, Petter S. Woll, Johanna Olweus
Summary: The study identifies a T cell receptor reactive against a driver mutation in FLT3 in acute myeloid leukemia and demonstrates the efficacy of engineered T cells against this mutation in immunotherapy.
Article
Hematology
Maryan M. Ali, Tobias Gedde-Dahl, Liv T. Osnes, Flavie Perrier, Marit B. Veierod, Geir E. Tjonnfjord, Per O. Iversen
Summary: Allogeneic hematopoietic stem cell transplantation is an effective treatment for hematologic malignancies, but graft-versus-host disease (GVHD) is a major challenge. Extracorporeal photopheresis (ECP) is a commonly used treatment for GVHD, but its use for GVHD prevention is limited. This randomized controlled trial found no significant difference in GVHD prevention between ECP and standard drug-based prophylaxis.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)