Article
Medicine, General & Internal
Shih-Lung Chen, Kai-Chieh Chan
Summary: ALCL is a rare form of non-Hodgkin's lymphoma, especially when it occurs in the external auditory canal (EAC). Diagnosis of ALCL in the EAC region can be challenging, but a combination of imaging, histopathological examination and IHC staining can confirm the presence of the disease. Treatment options include radiotherapy, chemoradiotherapy, and targeted therapies like Brentuximab vedotin for ALK-positive ALCL.
Review
Oncology
Xin-Rui Zhang, Pham-Ngoc Chien, Sun-Young Nam, Chan-Yeong Heo
Summary: Anaplastic large cell lymphoma is a rare disease with four subtypes that differ in clinical symptoms, gene changes, prognosis, and treatment.
Article
Multidisciplinary Sciences
Tongqing Li, Steven E. Stayrook, Yuko Tsutsui, Jianan Zhang, Yueyue Wang, Hengyi Li, Andrew Proffitt, Stefan G. Krimmer, Mansoor Ahmed, Olivia Belliveau, Ian X. Walker, Krishna C. Mudumbi, Yoshihisa Suzuki, Irit Lax, Diego Alvarado, Mark A. Lemmon, Joseph Schlessinger, Daryl E. Klein
Summary: The proto-oncogene ALK encodes anaplastic lymphoma kinase, which is primarily expressed in the developing nervous system. Its activity is associated with learning and memory, energy expenditure, and obesity prevention. Aberrant ALK signaling causes various cancers, including being a driver in pediatric neuroblastoma. The study reveals the crystal structures of ALK's extracellular glycine-rich domain (GRD) and how it regulates receptor activity, providing insights into potential therapeutics for ALK-expressing cancers.
Article
Multidisciplinary Sciences
Andrey V. Reshetnyak, Paolo Rossi, Alexander G. Myasnikov, Munia Sowaileh, Jyotidarsini Mohanty, Amanda Nourse, Darcie J. Miller, Irit Lax, Joseph Schlessinger, Charalampos G. Kalodimos
Summary: ALK is a receptor tyrosine kinase that regulates important functions in the central nervous system, and mutations in this gene may lead to neuroblastoma. Research has revealed a mechanism of RTK activation that allows dimerization by different ligands, with the complex architecture of the receptor-ligand complex playing a key role in this process.
Review
Immunology
Ye Guo, Hanfei Guo, Yongfei Zhang, Jiuwei Cui
Summary: Alterations in the ALK gene are crucial in the development of various tumors, and targeted therapy has transformed the treatment approach. However, resistance remains a challenge. ALK gene variants have a significant impact on the tumor immune microenvironment, suggesting potential clinical applications for immunotherapy targeting ALK-altered tumors.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Giulia Mura, Elif Karaca Atabay, Matteo Menotti, Cinzia Martinengo, Chiara Ambrogio, Gloria Giacomello, Maddalena Arigoni, Martina Olivero, Raffaele A. Calogero, Roberto Chiarle, Claudia Voena
Summary: Anaplastic Large Cell Lymphoma (ALCL) is driven by the chimeric tyrosine kinase NPM-ALK, which downregulates the expression of CD45 via STAT3 and acts as a rheostat of ALK oncogenic signaling and resistance to TKI treatment. CD45 is a key regulator of T cell activation and cytokine responses through the JAK/STAT pathway. In ALK+ ALCL, NPM-ALK inhibits T cell molecules expression and activates surrogate TCR signaling. Inhibition of NPM-ALK kinase activity leads to increased expression of CD45RO isoform. Knocking-out CD45 results in increased resistance to ALK TKI treatment.
FRONTIERS IN ONCOLOGY
(2023)
Article
Hematology
Elif Karaca Atabay, Carmen Mecca, Qi Wang, Chiara Ambrogio, Ines Mota, Nina Prokoph, Giulia Mura, Cinzia Martinengo, Enrico Patrucco, Giulia Leonardi, Jessica Hossa, Achille Pich, Luca Mologni, Carlo Gambacorti-Passerini, Laurence Brugieres, Birgit Geoerger, Suzanne D. Turner, Claudia Voena, Taek-Chin Cheong, Roberto Chiarle
Summary: This study identified PTPN1 and PTPN2 phosphatases as drivers of resistance to ALK TKIs in ALK(+) ALCL. These phosphatases regulate ALK phosphorylation and activity, and their loss leads to TKI resistance. Furthermore, SHP2 is a key mediator of oncogenic ALK signaling, and PTPN1 acts as a phosphatase for SHP2. Combination therapy with a SHP2 inhibitor can overcome TKI resistance in ALK(+) ALCL.
Article
Oncology
Takafumi Fukui, Motoko Tachihara, Tatsuya Nagano, Kazuyuki Kobayashi
Summary: Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) has made significant progress in recent years with the development of multiple tyrosine kinase inhibitors (TKIs) targeting ALK. Clinical trials of novel ALK-TKIs, angiogenesis inhibitors, immune checkpoint inhibitors, and chemotherapy are ongoing, and tissue and liquid biopsy are being explored as methods to investigate resistance mechanisms. This manuscript aims to provide information on these recent clinical trials and propose a treatment algorithm for ALK-rearranged advanced NSCLC.
Article
Oncology
Wei Wei, Zhihui Song, Masahiro Chiba, Wenjun Wu, Subin Jeong, Jing-Ping Zhang, Marshall E. Kadin, Masao Nakagawa, Yibin Yang
Summary: This study reveals the distinct roles of EP300 and CREBBP in ALCL and HL, with EP300 directly modulating the expression of oncogenes and immune-related molecules. The use of EP300/CREBBP inhibitors shows strong activities against ALCL and HL cells and inhibits tumor immune escape through PD-L1.
Article
Hematology
Zhihui Song, Wenjun Wu, Wei Wei, Wenming Xiao, Michelle Lei, Kathy Q. Cai, Da Wei Huang, Subin Jeong, Jing-Ping Zhang, Hongbo Wang, Marshall E. Kadin, Thomas A. Waldmann, Louis M. Staudt, Masao Nakagawa, Yibin Yang
Summary: This study revealed the critical role of the interleukin-1R (IL-1R) inflammatory pathway in pC-ALCL and its potential as a therapeutic target. The IL-1R pathway was found to promote JAK-STAT3 signaling activation and enhance the sensitivity of pC-ALCL cells to JAK inhibitors. The dual inhibitor pacritinib showed strong activities against pC ALK(-) ALCL in vitro and in vivo.
Article
Chemistry, Multidisciplinary
Luca Mologni, Sebastien Tardy, Alfonso Zambon, Alexandre Orsato, William H. Bisson, Monica Ceccon, Michela Viltadi, Joseph D'Attoma, Sara Pannilunghi, Vito Vece, Jerome Bertho, Peter Goekjian, Leonardo Scapozza, Carlo Gambacorti-Passerini
Summary: A series of azacarbazole inhibitors were designed, synthesized, and evaluated, with compound 149 showing selective inhibition of both native and drug-resistant mutants of the ALK kinase. The three-dimensional structure of a 149:ALK-KD cocrystal revealed extensive interaction through the hinge region and the catalytic lysine 1150, demonstrating its potential as a promising therapeutic candidate.
Article
Multidisciplinary Sciences
Huan-Chang Liang, Mariantonia Costanza, Nicole Prutsch, Mark W. Zimmerman, Elisabeth Gurnhofer, Ivonne A. Montes-Mojarro, Brian J. Abraham, Nina Prokoph, Stefan Stoiber, Simone Tangermann, Cosimo Lobello, Jan Oppelt, Ioannis Anagnostopoulos, Thomas Hielscher, Shahid Pervez, Wolfram Klapper, Francesca Zammarchi, Daniel-Adriano Silva, K. Christopher Garcia, David Baker, Martin Janz, Nikolai Schleussner, Falko Fend, Sarka Pospisilova, Andrea Janikova, Jacqueline Wallwitz, Dagmar Stoiber, Ingrid Simonitsch-Klupp, Lorenzo Cerroni, Stefano Pileri, Laurence de Leval, David Sibon, Virginie Fataccioli, Philippe Gaulard, Chalid Assaf, Fabian Knorr, Christine Damm-Welk, Wilhelm Woessmann, Suzanne D. Turner, A. Thomas Look, Stephan Mathas, Lukas Kenner, Olaf Merkel
Summary: The study highlights the importance of the BATF3/IL-2R module in ALCL biology and identifies IL-2R alpha targeting as a promising treatment strategy for ALCL.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
V. Subbiahy, S. Kuraviy, S. Ganguly, D. R. Welch, C. J. Vivian, M. U. Mushtaq, A. Hegde, S. Iyer, A. Behrang, S. M. Ali, R. W. Madison, J. M. Venstrom, R. A. Jensen, J. P. McGuirk, H. M. Amin, R. Balusu
Summary: The study demonstrates that Ceritinib shows inhibitory effects on the fusion kinase NPM1-ALK and induces apoptosis of lymphoma cells in vitro and in vivo. Treatment with Ceritinib in the NPM1-ALKthorn ALCL xenograft model resulted in tumor regression and improved survival. Among 19,272 patients sequenced, 0.30% harbored ALK fusions, including various hematologic malignancies.
Article
Nutrition & Dietetics
Simona Dedoni, Maria Scherma, Chiara Camoglio, Carlotta Siddi, Walter Fratta, Paola Fadda
Summary: The expression of ALK receptor is reduced in rats with activity-based anorexia, indicating a potential involvement of ALK receptor in the pathophysiology of anorexia nervosa.
Review
Immunology
Jennifer E. Agrusa, Emily R. Egress, Eric J. Lowe
Summary: ALCL is the most common mature T-cell non-Hodgkin lymphoma in children/adolescents, and improved therapies are needed. Brentuximab vedotin, an anti-CD30 antibody-drug conjugate, has shown safety and efficacy in clinical trials for ALCL in both pediatric and adult populations. Future studies should investigate combination therapies with brentuximab vedotin and other targeted agents.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pathology
Shaoxiong Chen, Melissa Randolph, Harvey M. Cramer, Tracy Watkins, Holly McCullough, Kristin M. Post, Joyashree D. Sen, Liang Cheng, Howard H. Wu
Article
Oncology
Melissa L. Randolph, Howard H. Wu, William N. Crabtree
CANCER CYTOPATHOLOGY
(2014)
Article
Biochemical Research Methods
A. Ermel, B. Qadadri, A. Morishita, I. Miyagawa, G. Yamazaki, B. Weaver, W. Tu, Y. Tong, M. Randolph, H. Cramer, D. Brown
JOURNAL OF VIROLOGICAL METHODS
(2010)
Article
Pathology
Howard H. Wu, Joseph P. Eaton, Kelly J. Jones, Harvey M. Cramer, Melissa L. Randolph, Kristin M. Post, Amanda Malek, Sarah Bilbo, Joyashree D. Sen, Shaoxiong Chen, Liang Cheng
Article
Oncology
Kristin A. La Fortune, Melissa L. Randolph, Howard H. Wu, Harvey M. Cramer
CANCER CYTOPATHOLOGY
(2017)
Article
Medical Laboratory Technology
Robert E. Emerson, Melissa L. Randolph, Harvey M. Cramer
DIAGNOSTIC CYTOPATHOLOGY
(2006)
