Review
Biochemistry & Molecular Biology
Agnieszka Kaczmarska, Patrycja Sliwa, Joanna Zawitkowska, Monika Lejman
Summary: Pediatric acute lymphoblastic leukemia (ALL) with t(9;22)(q34;q11.2) is a rare malignancy in children, with approximately 3-5% of patients having the Philadelphia chromosome. Treatment outcomes have improved significantly in recent years, with tyrosine kinase inhibitor (TKI)-imatinib playing a key role in increasing overall survival for ALL Ph+ patients. Genetic analyses, particularly focusing on the IKZF1 gene, provide important prognostic information for pediatric ALL Ph+ cases, highlighting the need for targeted therapies and immunotherapy to enhance patient outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Ibrahim Aldoss, Zhaohui Gu, Michelle Afkhami, Sally Mokhtari, Vinod Pullarkat
Summary: Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk subgroup of B-cell ALL with distinct genotypes, similar to Ph-positive ALL but lacking the BCR::ABL1 fusion. Ph-like ALL patients have poor responses to conventional chemotherapy and lower survival rates compared to other B-cell ALL subtypes. Innovative therapeutic approaches, such as tyrosine kinase inhibitors, antibody-drug conjugates, and immunotherapies, are being explored for the treatment of Ph-like ALL. Accurate diagnosis and risk stratification are crucial for improving outcomes and increasing access to hematopoietic cell transplantation for high-risk patients in their first complete remission.
LEUKEMIA & LYMPHOMA
(2023)
Article
Hematology
Shunsuke Kimura, Lindsey Montefiori, Ilaria Iacobucci, Yaqi Zhao, Qingsong Gao, Elisabeth M. Paietta, Claudia Haferlach, A. Douglas Laird, Paul E. Mead, Zhaohui Gu, Wendy Stock, Mark Litzow, Jacob M. Rowe, Selina M. Luger, Stephen P. Hunger, Georgina L. Ryland, Breon Schmidt, Paul G. Ekert, Alicia Oshlack, Sean M. Grimmond, Jacqueline Rehn, James Breen, David Yeung, Deborah L. White, Ibrahim Aldoss, Elias J. Jabbour, Ching-Hon Pui, Manja Meggendorfer, Wencke Walter, Wolfgang Kern, Torsten Haferlach, Samuel Brady, Jinghui Zhang, Kathryn G. Roberts, Piers Blombery, Charles G. Mullighan
Summary: This study identified a previously unrecognized high-risk subtype of B-ALL using transcriptome and whole-genome sequencing. The subtype is characterized by specific gene expression profile and genomic alterations caused by abnormal activation of recombination-activating genes (RAG). It is associated with high-risk clinical features.
Article
Hematology
Daniela R. Anderson, Wendy Stock, Theodore G. Karrison, Avi Leader
Summary: The level of D-dimer is associated with the risk of venous or arterial thrombosis in patients with ALL within 100 days after diagnosis.
Article
Oncology
Danna Lin, Keyan Yang, Lihua Yu, Lulu Huang, Xiaorong Lai, Li Wu, Xiayu Xia, Jingwen Zhang, Qinlong Zheng, Lihua Yang
Summary: This study retrospectively analyzed the prognostic impact of CRLF2 expression level on pediatric B-ALL patients and found that CRLF2 overexpression could be divided into two categories based on expression levels, which were associated with prognosis. The study highlights the importance of the molecular mechanisms of upregulated CRLF2 expression in predicting the prognosis of pediatric B-ALL patients.
FRONTIERS IN ONCOLOGY
(2023)
Review
Genetics & Heredity
Ilaria Iacobucci, Kathryn G. Roberts
Summary: Ph-like acute lymphoblastic leukemia is a subgroup of B-cell precursor ALL that shares similarities with Philadelphia-positive ALL but lacks the BCR-ABL1 oncogenic protein. The genetic alterations in Ph-like ALL are highly heterogeneous, including gene fusions, sequence mutations, and DNA copy number changes. Patients with Ph-like ALL often have poor response to conventional therapeutic approaches.
Article
Oncology
Khalid Halahleh, Isra Muradi, Mohammad Zakaria Khalil, Lina Halahleh, Maher Sughayer, Nazmi Kamal, Iyad Sultan, Kamal Alrabi
Summary: ETP-ALL/LBL is a high-risk subtype of adult ALL, and the optimal therapeutic approaches for adult patients have not been well studied.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Article
Medicine, Research & Experimental
Filip Matthijssens, Nitesh D. Sharma, Monique Nysus, Christian K. Nickl, Huining Kang, Dominique R. Perez, Beatrice Lintermans, Wouter Van Loocke, Juliette Roels, Sofie Peirs, Lisa Demoen, Tim Pieters, Lindy Reunes, Tim Lammens, Barbara De Moerloose, Filip Van Nieuwerburgh, Dieter L. Deforce, Laurence C. Cheung, Rishi S. Kotecha, Martijn D. P. Risseeuw, Serge Van Calenbergh, Takeshi Takarada, Yukio Yoneda, Frederik W. van Delft, Richard B. Lock, Seth D. Merkley, Alexandre Chigaev, Larry A. Sklar, Charles G. Mullighan, Mignon L. Loh, Stuart S. Winter, Stephen P. Hunger, Steven Goossens, Eliseo F. Castillo, Wojciech Ornatowski, Pieter Van Vlierberghe, Ksenia Matlawska-Wasowska
Summary: The study demonstrates that the upregulation of RUNX2 acts as a dependency factor in high-risk subtypes of human T-ALL by regulating tumor metabolism and leukemic cell migration simultaneously.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Oncology
Zheng Ge, Chunhua Song, Yali Ding, Bi-Hua Tan, Dhimant Desai, Arati Sharma, Raghavendra Gowda, Feng Yue, Suming Huang, Vladimir Spiegelman, Jonathon L. Payne, Mark E. Reeves, Soumya Iyer, Pavan Kumar Dhanyamraju, Yuka Imamura, Daniel Bogush, Yevgeniya Bamme, Yiping Yang, Mario Soliman, Shriya Kane, Elanora Dovat, Joseph Schramm, Tommy Hu, Mary McGrath, Zissis C. Chroneos, Kimberly J. Payne, Chandrika Gowda, Sinisa Dovat
Summary: IKAROS functions as a transcriptional repressor of MTOR gene in treating HR B-ALL, which can be enhanced by the CK2 inhibitor CX-4945. The combining of CX-4945 with rapamycin shows novel synergistic therapeutic effects in reducing MTOR expression and treating Hispanic/Latino children with HR B-ALL. Dual targeting of oncogene transcription along with oncoprotein inhibition could provide a precision medicine approach for hematological malignancies.
Article
Hematology
Eman O. Rasekh, Randa Osman, Dalia Ibraheem, Youssef Madney, Enas Radwan, Abdallah Gameel, Ahmed Abdelhafiz, Azza Kamel, Sally Elfishawi
Summary: Mixed phenotype acute leukemia (MPAL) is a rare type of leukemia with different cell phenotypes. Studies suggest that ALL-like treatment regimen shows better response in MPAL patients, and there are similarities in clinical features between adult and pediatric patients.
ANNALS OF HEMATOLOGY
(2021)
Article
Oncology
Hayden L. Bell, Helen J. Blair, Mankaran Singh, Anthony V. Moorman, Olaf Heidenreich, Frederik W. van Delft, John Lunec, Julie A. E. Irving
Summary: This study found that the WEE1 inhibitor adavosertib can effectively inhibit the growth of leukemia cells in high-risk and relapsed ALL patients, particularly in tumors with TP53 mutations. Additionally, adavosertib in combination with current chemotherapy drugs used for relapsed ALL can synergistically enhance the treatment efficacy. These findings suggest that WEE1 could be a promising therapeutic target for high-risk and relapsed ALL, independent of p53 status.
CANCER CELL INTERNATIONAL
(2023)
Review
Pediatrics
Shuvadeep Ganguly, Archana Sasi, Deepam Pushpam, Sameer Bakhshi
Summary: This article describes the diagnosis and treatment methods of Philadelphia chromosome positive acute lymphoblastic lymphoma (Ph+ ALL) in children, including conventional karyotyping and BCR-ABL1 translocation detection, as well as using chemotherapy and hematopoietic stem cell transplantation to control and treat the disease.
INDIAN JOURNAL OF PEDIATRICS
(2023)
Review
Oncology
Francesco Tamiro, Andrew P. Weng, Vincenzo Giambra
Summary: Leukemia-initiating cells (LIC) are unique cells in different types of leukemia that have self-renewing capabilities and produce tumors, which are functionally distinct from bulk leukemia cells. Current conventional treatments are not effective in eliminating LICs, hence innovative therapeutics targeting LICs hold promise for developing an effective cure for ALL.
Article
Biotechnology & Applied Microbiology
Li-Jun Peng, Yue-Bo Zhou, Mei Geng, Ekaterina Bourova-Flin, Florent Chuffart, Wei-Na Zhang, Tao Wang, Meng-Qing Gao, Meng-Ping Xi, Zhong-Yi Cheng, Jiao-Jiao Zhang, Yuan-Fang Liu, Bing Chen, Saadi Khochbin, Jin Wang, Sophie Rousseaux, Jian-Qing Mi
Summary: By discovering 18 genes associated with shorter survival, we have developed a prognostic classifier for T-ALL patients that can improve therapeutic decisions. Additionally, our study has revealed specific biological characteristics of aggressive T leukemic cells, providing insights for better understanding and management of the disease.
Review
Oncology
Khalil Saleh, Alexis Fernandez, Florence Pasquier
Summary: The outcome of patients with Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) has dramatically improved in the past 20 years with the introduction of tyrosine kinase inhibitors and monoclonal antibodies. These treatments have shown great efficacy in young and fit patients, leading to questioning the reliance on chemotherapy and stem cell transplantation. They can also be safely used in elderly patients, who make up the majority of Ph+ ALL patients. This review focuses on the recent changes in the management of Ph+ ALL patients and the development of new therapeutic strategies.
Article
Hematology
David Spencer Mangum, Johnathon D. Bishop, Yinmei Zhou, Cheng Cheng, Seth E. Karol, Jeffrey E. Rubnitz, Raul C. Ribeiro, Jun J. Yang, Charles G. Mullighan, Sima Jeha, Ching-Hon Pui, Hiroto Inaba
Summary: Among children with acute lymphoblastic leukaemia, about 14.7% presented without peripheral blood blasts. While absence of blasts did not affect survival outcomes, these patients had distinct genetic and clinical characteristics, with a higher incidence of hyperdiploid B-ALL and lower rates of central nervous system involvement.
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.
Review
Pathology
Amy S. Duffield, Charles G. Mullighan, Michael J. Borowitz
Summary: The updated International Consensus Classification (ICC) of B-acute lymphoblastic leukemia (B-ALL) and T-acute lymphoblastic leukemia (T-ALL) includes revisions to previous subtypes and new entities. The classification incorporates recent clinical, cytogenetic, and molecular data, emphasizing whole transcriptome analysis and gene expression clustering studies. The new classification allows for improved risk stratification and optimized treatment plans for ALL patients.
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.
Letter
Hematology
Olga K. Weinberg, Daniel A. Arber, Hartmut Doehner, Charles G. Mullighan, Etan Orgel, Anna Porwit, Richard M. Stone, Michael J. Borowitz
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
Satoshi Yoshimura, John C. Panetta, Jianzhong Hu, Lie Li, Yoshihiro Gocho, Guoqing Du, Akihiro Umezawa, Seth E. Karol, Ching-Hon Pui, Charles G. Mullighan, Marina Konopleva, Wendy Stock, David T. Teachey, Nitin Jain, Jun J. Yang
Summary: LCK is a therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL), and dasatinib and ponatinib are effective inhibitors of LCK. This study evaluates the pharmacokinetics and pharmacodynamics of dasatinib and ponatinib in LCK-activated T-ALL. Both drugs demonstrate similar cytotoxic activity, with ponatinib being slightly more potent. Ponatinib exhibits slower clearance and higher exposure compared to dasatinib. Exposure-to-response models suggest that both drugs achieve significant pLCK inhibition, comparable to their effects in other leukemias. Additionally, ponatinib retains partial activity against LCK in a dasatinib-resistant T-ALL cell line model. Overall, this study provides crucial data for the development of human trials involving dasatinib and ponatinib in T-ALL.
Article
Multidisciplinary Sciences
Mohsen Fathi, Melisa Martinez-Paniagua, Ken Chen, Ali Rezvan, Melisa J. Montalvo, Vakul Mohanty, Sendurai A. Mani, Navin Varadarajan
Summary: Excitatory cells play an important role in the neuronal circuits underlying feeding behavior in Drosophila. We show here that the activity of a subset of excitatory neurons expressing either neuropeptide F (NPF) or short neuropeptide F (sNPF) in the adult Drosophila brain is necessary for sleep homeostasis. These neurons promote sleep primarily through output signals downstream of the mushroom body output neurons.
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)
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)