Article
Oncology
Bryann Pardieu, Justine Pasanisi, Frank Ling, Reinaldo Dal Bello, Justine Penneroux, Angela Su, Romane Joudinaud, Laureen Chat, Hsin Chieh Wu, Matthieu Duchmann, Gaetano Sodaro, Clementine Chauvel, Florence A. Castelli, Loic Vasseur, Kim Pacchiardi, Yannis Belloucif, Marie-Charlotte Laiguillon, Eshwar Meduri, Camille Vaganay, Gabriela Alexe, Jeannig Berrou, Chaima Benaksas, Antoine Forget, Thorsten Braun, Claude Gardin, Emmanuel Raffoux, Emmanuelle Clappier, Lionel Ades, Hugues de The, Francois Fenaille, Brian J. Huntly, Kimberly Stegmaier, Herve Dombret, Nina Fenouille, Camille Lobry, Alexandre Puissant, Raphael Itzykson
Summary: By analyzing multiple AML datasets, we identified SLC7A11 as a potential gene that is essential for AML cell survival. Inhibition of SLC7A11 using genetic and chemical methods reduced the viability and clonogenic capacity of AML cell lines. Sulfasalazine, a drug with xCT inhibitory activity, showed anti-leukemic effects against primary AML samples in vitro. Inhibition of xCT affected multiple metabolic pathways, leading to depletion of glutathione pools and oxidative stress-induced cell death in leukemic cells.
Article
Oncology
Jae Won Yoo, Suejung Jo, Moon Bae Ahn, Seongkoo Kim, Jae Wook Lee, Myungshin Kim, Bin Cho, Nack-Gyun Chung
Summary: Tyrosine kinase inhibitors are effective in treating pediatric patients with chronic myeloid leukemia, however, there is insufficient evidence to determine the superiority of one inhibitor over another. Our study compared the efficacy and safety profiles of two front-line tyrosine kinase inhibitors in pediatric patients. Both inhibitors showed good cytogenetic response rates at 12 months, but dasatinib had significantly higher molecular response rates. Both inhibitors were well tolerated, but dasatinib was associated with a greater decline in height.
Article
Oncology
Ehab Atallah, Michael J. Mauro, Andreas Hochhaus, Carla Boquimpani, Yosuke Minami, Vikalp Kumar Maheshwari, Lovneet Saini, Regina Corbin, Delphine Rea
Summary: The current standard of care for CP-CML is TKIs, but treatment recommendations for patients failing >= 2 lines of treatment are unclear. This study compared asciminib with other TKIs in >= 3L CP-CML through matching-adjusted indirect comparisons. The results showed favorable outcomes with asciminib, suggesting its therapeutic potential in this patient population.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Oncology
Jorge Cortes, Fabian Lang
Summary: CML is driven by the BCR-ABL1 fusion protein, making the ATP binding site of ABL1 an optimal target for TKIs. Despite improvements in prognosis, patients often fail treatment and require new therapeutic options.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Oncology
Timothy P. Hughes, Nelma Cristina D. Clementino, Mikhail Fominykh, Jeffrey H. Lipton, Anna G. Turkina, Elena Beatriz Moiraghi, Franck E. Nicolini, Naoto Takahashi, Tomasz Sacha, Dong-Wook Kim, Rafik Fellague-Chebra, Ranjan Tiwari, Catherine Bouard, Francois-Xavier Mahon
Summary: The ENESTop study demonstrated the durability and safety of treatment-free remission (TFR) in chronic myeloid leukemia patients who achieved sustained deep molecular response with nilotinib. Overall adverse event rates decreased over 5 years of TFR, but there was a cumulative increase in cardiovascular events with longer nilotinib exposure when reinitiating treatment.
Article
Biochemistry & Molecular Biology
Indira Singaram, Ashutosh Sharma, Shashank Pant, Muyun Lihan, Mi-Jeong Park, Melissa Pergande, Pawanthi Buwaneka, Yusi Hu, Nadim Mahmud, You-Me Kim, Stephanie Cologna, Vladimir Gevorgyan, Irum Khan, Emad Tajkhorshid, Wonhwa Cho
Summary: Membrane lipids control the cellular activity of kinases containing the SH2 domain. In this study, new nonlipidic small molecule inhibitors of the lipid-SH2 domain interaction were developed to block the cellular activity of their host proteins. The research shows that targeting lipid-protein interaction is a powerful approach to developing new small molecule drugs.
NATURE CHEMICAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Binoy Yohannan, Binsah George
Summary: This article provides a comprehensive summary of the current management of Lymphoid Blast Crisis (BC), which is one of the most feared complications of chronic myeloid leukemia (CML). The incidence of BC has significantly decreased in the BCR-ABL tyrosine kinase inhibitor era, but there is still a need for novel therapies to improve the clinical outcomes of patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Jiasheng Wang, Benjamin Tomlinson, Hillard M. Lazarus
Summary: The search for effective therapies for the highly heterogenous disease acute myeloid leukemia (AML) has been difficult. However, sophisticated molecular studies have identified defects within AML cells that can be targeted using small molecule agents, leading to the development of several FDA-approved medications. Additionally, emerging small molecules offer new treatment options for AML, and the combination of these agents with cytotoxic drugs and immunotherapy may further improve outcomes.
CURRENT TREATMENT OPTIONS IN ONCOLOGY
(2023)
Article
Oncology
Fadi G. Haddad, Hagop M. Kantarjian, Aram Bidikian, Elias J. Jabbour, Nicholas J. Short, Jing Ning, Lianchun Xiao, Naveen Pemmaraju, Courtney D. DiNardo, Tapan M. Kadia, Kayleigh R. Marx, Guillermo Garcia-Manero, Farhad Ravandi, Koji Sasaki, Ghayas C. Issa
Summary: Bariatric surgery has a negative impact on the treatment outcomes of patients with chronic myeloid leukemia, leading to lower early molecular response rates, longer time to achieve complete cytogenetic or major molecular responses, and lower survival rates.
Review
Hematology
Sabine Kayser, Mark J. Levis
Summary: Research on the pathogenic mechanisms of AML has made remarkable advances in recent years, especially in the importance of cytogenetic and molecular aberrations. The development of new compounds targeting AML at a molecular level, based on increased understanding of AML pathogenesis facilitated by next-generation sequencing, has turned many hopeful predictions into therapeutic realities.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Review
Pharmacology & Pharmacy
Gustavo P. Amarante-Mendes, Aamir Rana, Tarcila Santos Datoguia, Nelson Hamerschlak, Gabriela Brumatti
Summary: The constitutively active BCR-ABL1 tyrosine kinase plays a role in leukemia and initiates a complex signaling transduction cascade. Tyrosine kinase inhibitors have revolutionized the treatment of CML, but complete cure is not achieved. Other mechanisms exist in the later stages of the disease.
Review
Chemistry, Multidisciplinary
Tianyuan Ci, Wentao Zhang, Yingyu Qiao, Huangjuan Li, Jing Zang, Hongjun Li, Nianping Feng, Zhen Gu
Summary: This review discusses the current state and advances in anti-leukemia drugs and therapies, with a focus on the development of drug delivery systems for leukemia treatment. These delivery systems improve the pharmacokinetics of drugs in vivo, targeting specific cells or tumor microenvironment and reversing drug resistance, leading to enhanced tumor elimination and reduced adverse effects.
CHEMICAL SOCIETY REVIEWS
(2022)
Review
Oncology
Fadi Haddad, Amer M. Zeidan, Naval Daver
Summary: Immune checkpoint inhibitors have shown relatively low objective response rates in AML, but have demonstrated durable stable disease and hematologic improvement in a subset of patients. Novel AML and myelodysplastic syndrome-specific checkpoints, as well as anti-CD47/SIRP alpha therapy, show promising efficacy and safety, particularly in TP53-mutated AML. Other T cell-based immune therapies are also being investigated.
Review
Cell & Tissue Engineering
Hanieh Mojtahedi, Niloufar Yazdanpanah, Nima Rezaei
Summary: CML is driven by the BCR-ABL1 oncoprotein, and TKI therapy has been successful. However, mechanisms leading to resistance and disease progression in CML LSCs call for targeted therapies to eradicate them.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Chemistry, Multidisciplinary
Yangyang Du, Mingda Han, Kunxia Cao, Qing Li, Jiuxia Pang, Liping Dou, Shujun Liu, Zhan Shi, Fei Yan, Shouhua Feng
Summary: Reprogramming the m(6)A landscape using gold nanorods selectively taken up by leukemia cells inhibits leukemia cell growth by disrupting redox balance and inducing ferroptosis. The nanorods abrogate endogenous m(6)A demethylase activity, leading to global m(6)A hypomethylation and post-transcriptional regulation of downstream genes. Combination treatment with the nanorods and tyrosine kinases inhibitors synergistically overcomes m(6)A-mediated TKI resistance and enhances immunotherapy outcome in leukemia.
Article
Hematology
Jochen J. Frietsch, Sarah Flossdorf, James F. Beck, Nicolaus Kroeger, Katharina Fleischhauer, Peter Dreger, Johannes Schetelig, Martin Bornhaeuser, Andreas Hochhaus, Inken Hilgendorf
Summary: This retrospective analysis examined the outcomes of young adults who underwent allogeneic haematopoietic stem cell transplantation (HSCT) in Germany. The study found that the outcomes of young adults after HSCT improved over time and were influenced by factors such as underlying disease, age at disease onset, stem cell source, and donor type. However, the survival rate of HSCT recipients after 10 years was significantly lower compared to the general population of young adults.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
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
Oncology
Jorge E. Cortes, Andreas Hochhaus, Naoto Takahashi, Richard A. Larson, Ghayas C. Issa, Felice Bombaci, Nicholas Ramscar, Sophie Ifrah, Timothy P. Hughes
Summary: Asciminib, a BCR-ABL1 inhibitor that works through the STAMP mechanism, has shown favorable efficacy and safety in patients with chronic myeloid leukemia in chronic phase. The ongoing ASC4FIRST trial aims to compare the effectiveness of Asciminib with investigator-selected TKIs in newly diagnosed patients with chronic myeloid leukemia.
Article
Oncology
Andreas Hochhaus, Delphine Rea, Carla Boquimpani, Yosuke Minami, Jorge E. Cortes, Timothy P. Hughes, Jane F. Apperley, Elza Lomaia, Sergey Voloshin, Anna Turkina, Dong-Wook Kim, Andre Abdo, Laura Maria Fogliatto, Philipp le Coutre, Koji Sasaki, Dennis Dong Hwan Kim, Susanne Saussele, Mario Annunziata, Naeem Chaudhri, Lynette Chee, Valentin Garcia-Gutierrez, Shruti Kapoor, Alex Allepuz, Sara Quenet, Veronique Bedoucha, Michael J. Mauro
Summary: Asciminib, a BCR-ABL1 inhibitor that targets the ABL Myristoyl Pocket (STAMP), is approved worldwide for the treatment of adults with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (CML-CP) who have been previously treated with at least 2 tyrosine kinase inhibitors (TKIs). In the ASCEMBL study, asciminib demonstrated superior efficacy and better safety and tolerability compared to bosutinib in patients with CML-CP who had received at least 2 prior TKIs. The major molecular response rate at week 96 was significantly higher with asciminib than with bosutinib, and fewer adverse events and treatment discontinuations were observed with asciminib.
Article
Urology & Nephrology
Camilo Montero, Nancy Yomayusa, Rodolfo Torres, Jorge Cortes, Carlos Alvarez, Juan Gallo, Guillermo Aldana, Andres Acevedo, Maria Rios, Johana Echeverri, Zuly Yepes, Adriana Silva, Diana Gayon, Jorge Perez, Milciades Ibanez
Summary: This study aimed to evaluate asymptomatic CMV reactivation and CMV disease in kidney transplant recipients with positive CMV serostatus. The results showed that asymptomatic CMV reactivation was higher in patients who received thymoglobulin induction, while the rates of CMV disease were similar between the two treatment groups. The significant difference in asymptomatic CMV reactivation between the two groups did not affect graft function and histology.
Article
Oncology
Michael J. Mauro, Timothy P. Hughes, Dong-Wook Kim, Delphine Rea, Jorge E. Cortes, Andreas Hochhaus, Koji Sasaki, Massimo Breccia, Moshe Talpaz, Oliver Ottmann, Hironobu Minami, Yeow Tee Goh, Daniel J. DeAngelo, Michael C. Heinrich, Valle Gomez-Garcia de Soria, Philipp le Coutre, Francois-Xavier Mahon, Jeroen J. W. M. Janssen, Michael Deininger, Naranie Shanmuganathan, Mark B. Geyer, Silvia Cacciatore, Fotis Polydoros, Nithya Agrawal, Matthias Hoch, Fabian Lang
Summary: Asciminib has been approved for patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CML-CP) who have received >= 2 prior tyrosine kinase inhibitors or have the T315I mutation. A phase 1 trial evaluated the safety and efficacy of asciminib monotherapy in 115 CML-CP patients without T315I. After a median exposure of approximately 4 years, most patients remained on asciminib and achieved significant molecular responses.
Article
Oncology
Fabio Efficace, Francesco Cottone, Betina Yanez, Vamsi Kota, Fausto Castagnetti, Giovanni Caocci, Massimiliano Bonifacio, Andrea Patriarca, Isabella Capodanno, Maria Cristina Miggiano, Mario Tiribelli, Massimo Breccia, Luigia Luciano, Valentina Giai, Alessandra Iurlo, Elisabetta Abruzzese, Carmen Fava, Shira Dinner, Jessica K. Altman, Gianantonio Rosti, Jorge Cortes, Marco Vignetti, David Cella
Summary: Patient-reported symptom monitoring from the beginning of therapy in patients with CML may be critical to improve adherence to therapy and early molecular response rates. The current findings suggest that systematic monitoring of patient-reported symptoms is associated with high adherence rates.
Article
Oncology
Koji Sasaki, Kiyomi Morita, Hagop Kantarjian, Guillermo Garcia-Manero, Elias Jabbour, Farhad Ravandi, Marina Konopleva, Gautam Borthakur, William Wierda, Naval Daver, Koichi Takahashi, Courtney Dinardo, Guillermo Montalban Bravo, Ghayas C. Issa, Sherry A. Pierce, Kelly A. Soltysiak, Martha S. Tingen, Jorge E. Cortes
Summary: This study investigated the impact of geographic disparities on cancer survival. The study found that factors such as age, income, race, and distance to cancer centers were predictive of survival. The results showed significant disparities in cancer care based on geographic locations.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Article
Virology
Pankaj Ahluwalia, Ashutosh Vashisht, Harmanpreet Singh, Nikhil Shri Sahajpal, Ashis K. Mondal, Kimya Jones, Jaspreet Farmaha, Ryan Bloomquist, Caroline Marie Carlock, Drew Fransoso, Christina Sun, Tyler Day, Comfort Prah, Trinh Vuong, Patty Ray, Danielle Bradshaw, Marisol Miranda Galvis, Sadanand Fulzele, Girindra Raval, Justin Xavier Moore, Jorge Cortes, Jeffrey N. James, Vamsi Kota, Ravindra Kolhe
Summary: This study aimed to investigate the temporal changes in the humoral immune response among healthcare workers in Augusta, GA, USA, and explore any associations with ethno-demographic features. The findings showed a significant decline in neutralizing antibody (NAb) and IgG levels at 8-12 months post-vaccination, with a more pronounced decline in White HCWs. Booster doses were found to increase antibody levels significantly, while participants without booster doses experienced a decline in antibody levels at 12 months post-vaccination.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Review
Hematology
Mahesh Swaminathan, Jorge E. E. Cortes
Summary: Gemtuzumab-ozogamicin (GO) is an ADC approved for the treatment of CD33(+) AML. Despite initial recall due to lack of efficacy and hepatotoxicities, subsequent phase 3 studies showed significant survival benefits with lower and fractionated doses of GO in combination with standard chemotherapy. GO at a dose of 6 mg/m(2) was associated with higher grade > 3 hepatotoxicities and VOD compared to 3 mg/m(2). GO has been reapproved in 2017 and is currently being studied for its role in combination therapies and MRD elimination in CD33(+) AML patients.
THERAPEUTIC ADVANCES IN HEMATOLOGY
(2023)
Meeting Abstract
Hematology
Gemma Shay, Michael W. Deininger, Tim H. Bruemmendorf, Jeffrey H. Lipton, Leif Stenke, Eric Leip, Simon Purcell, Andrea Viqueira, Jorge E. Cortes
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Meeting Abstract
Oncology
Richard F. Schlenk, Pau Montesinos, Antonio Romero-Aguilar, Radovan Vrhovac, Elzbieta Patkowska, Hee-Je Kim, Pavel Zak, Po-Nan Wang, James Hanyok, Li Liu, Yasser Mostafa Kamel, Arnaud Lesegretain, Jorge Cortes, Mikkael A. Sekeres, Herve Dombret, Sergio Amadori, Jianxiang Wang, Alexander E. Perl, Mark J. Levis, Harry P. Erba
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Meeting Abstract
Oncology
Muhannad Sharara, Kellen Cristine Tjioe, Marisol Miranda Galvis, Gagan Agrawal, Andrew Balas, Jorge Cortes
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Meeting Abstract
Oncology
Ana Toreli, Marisol Miranda-Galvis, Marcelo Addas-Carvalho, Eliana Miranda, Leonardo Fechio, Adriana Duarte, Audrey Basso, Gislaine Duarte, Samuel Medina, Fernando Pericole, Bruno Benites, Ravindra Kolhe, Kimya Jones, Harmanpreet Singh, Sara Teresinha Olalla Saad, Carmino Antonio de Souza, Jorge Cortes, Katia Pagnano
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Meeting Abstract
Oncology
Mark J. Levis, Harry P. Erba, Pau Montesinos, Radovan Vrhovac, Elzbieta Patkowska, Hee-Je Kim, Pavel Zak, Po-Nan Wang, Jaime E. Connolly Rohrbach, Ken C. N. Chang, James Hanyok, Li Liu, Yasser Mostafa Kamel, Arnaud Lesegretain, Jorge Cortes, Mikkael A. Sekeres, Herve Dombret, Sergio Amadori, Jianxiang Wang, Richard F. Schlenk, Alexander E. Perl
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)