Review
Biochemistry & Molecular Biology
Marc Gutierrez, Patrick Bladek, Busra Goksu, Carlos Murga-Zamalloa, Dale Bixby, Ryan Wilcox
Summary: T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells. Correct identification of T-PLL is essential because treatment for this disease is distinct from that of other T-cell neoplasms. The T-PLL International Study Group (TPLL-ISG) established criteria for the diagnosis and treatment of T-PLL, focusing on the role of TCL1 family members and ATM in disease pathogenesis. Despite improved understanding of disease pathogenesis, alemtuzumab remains the frontline therapy for T-PLL, but there is a need for novel therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Till Braun, Annika Dechow, Gregor Friedrich, Michael Seifert, Johanna Stachelscheid, Marco Herling
Summary: T-cell prolymphocytic leukemia (T-PLL) is a common and aggressive mature T-cell leukemia with resistance to chemotherapy. The constitutive transcriptional activation of the TCL1 gene family is a key event in its pathogenesis. New molecular dependencies and altered signaling pathways have been identified as hallmark features in recent years, providing insights for potential therapeutic interventions in T-PLL patients, both pre-clinically and clinically.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Elsa Poullot, Dina Milowich, Francois Lemonnier, Bettina Bisig, Cyrielle Robe, Laura Pelletier, Audrey Letourneau, Aurelie Dupuy, Nouhoum Sako, Nicolas Ketterer, Patrice Carde, Peggy Dartigues, Marie-Helene Delfau-Larue, Laurence de Leval, Philippe Gaulard
Summary: This study aims to investigate the association between AITL and HHV8 infection or KS. The results show that concurrent nodal involvement by AITL and KS is rare and can pose diagnostic challenges. Further research is needed to determine whether the association between AITL and KS is coincidental or related to underlying immune dysfunction in AITL.
Review
Oncology
Indumathy Varadarajan, Karen Ballen
Summary: This review summarizes the treatment of T-PLL, focusing on HSCT with alemtuzumab and its efficacy and complications. It also highlights the importance of patient selection and the complications before and after the transplant.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Andy Karabajakian, Isabelle Ray-Coquard, Jean-Yves Blay
Summary: Kaposi's sarcoma has multiple forms, with the HIV-related form being the most aggressive and involving different areas. Kaposi's sarcoma-associated herpes virus is the underlying cause of the disease, affecting host cell proliferation and angiogenesis, and also impacting immune response.
Article
Hematology
Milos D. Miljkovic, Sigrid P. Dubois, Bonita Bryant, Elaine Ma, Kevin C. Conlon, Thomas A. Waldmann
Summary: IL-15 monotherapy increases NK cell and CD8+ T cell numbers and activity, but lacks clinical responses. In a mouse model, IL-15 enhances NK cell-mediated ADCC of anti-CD52 antibody and produces more durable responses. A phase 1 study was conducted on patients with CD52-positive mature T-cell malignancies to determine if IL-15 potentiates ADCC in humans. IL-15 was given subcutaneously for 2 weeks followed by alemtuzumab. No dose-limiting toxicities were observed, and the overall response rate was 45% with a median duration of response of 6 months. IL-15 treatment resulted in increased NK cell activation markers and ADCC activity. The trial was registered at www.clinicaltrials.gov as #NCT02689453.
Article
Medicine, General & Internal
Jose Carvalho, Alexandra Esteves, Francisco Teixeira da Silva, Joana Couto, Carlos Ribeiro
Summary: T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive lymphoproliferative disorder, presenting with symptoms such as fatigue, anemia, and edema, eventually leading to rapid progression and death.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2021)
Article
Oncology
Paurnima Patil, Sina Hillebrecht, Emil Chteinberg, Cristina Lopez, Umut H. Toprak, Julian Seufert, Stephan H. Bernhart, Helene Kretzmer, Anke K. Bergmann, Susanne Bens, Josef Hoegel, Annika Mueller, Billy Michael Jebaraj, Alexandra Schrader, Patricia Johansson, Dolors Costa, Matthias Schlesner, Jan Duerig, Marco Herling, Elias Campo, Stephan Stilgenbauer, Laura Wiehle, Reiner Siebert
Summary: Deregulation of micro(mi)-RNAs is a common mechanism in tumorigenesis. In T-cell prolymphocytic leukemia (T-PLL), 111 miRNAs were found to be differentially expressed compared to normal T-cell subsets, with 33 of them belonging to cancer-related miRNA gene clusters. Upregulation of the miR-200c/-141 cluster in T-PLL was associated with DNA hypomethylation and active promoter marks, suggesting that copy number aberrations and epigenetic changes could contribute to miRNA deregulation in T-PLL.
GENES CHROMOSOMES & CANCER
(2022)
Article
Oncology
Sara R. R. Privatt, Owen Ngalamika, Jianshui Zhang, Qinsheng Li, Charles Wood, John T. T. West
Summary: Despite the widespread use of ART and decreased HIV incidence, Kaposi Sarcoma (KS) remains highly prevalent in certain regions. Currently, there are no preventative measures or curative therapies for KS. A study has identified potential biomarkers and therapeutic targets for KS based on transcriptomic profiles from KS lesions and validated the expression of certain glycoproteins in human KS lesions and KSHV-infected cell line-derived mouse xenografts.
Article
Oncology
Melitah Motlhale, Mazvita Muchengeti, Debbie Bradshaw, Wenlong Carl Chen, Mwiza Gideon Singini, Chantal Babb de Villiers, Cathryn M. M. Lewis, Noemi Bender, Christopher G. G. Mathew, Robert Newton, Tim Waterboer, Elvira Singh, Freddy Sitas
Summary: This study investigates the relationship between Kaposi sarcoma-associated herpesvirus (KSHV) infection, HIV-1 infection, and antiretroviral therapy (ART) rollout in South Africa. The findings show that KSHV seropositivity is higher in males and individuals with HIV, and lower in individuals with higher levels of education. KSHV seroprevalence decreases over time, coinciding with ART rollout and improvements in educational standards and hygiene.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Multidisciplinary Sciences
Shulan Tian, Henan Zhang, Pan Zhang, Michael Kalmbach, Jeong-Heon Lee, Tamas Ordog, Paul J. Hampel, Timothy G. Call, Thomas E. Witzig, Neil E. Kay, Eric W. Klee, Susan L. Slager, Huihuang Yan, Wei Ding
Summary: T-cell prolymphocytic leukemia is a rare disease with a potentially crucial role of epigenetic mechanisms in its pathogenesis. Research has shown a global alteration of regulatory landscape in T-PLL, suggesting epigenetic regulation may involve oncogenes, genes related to DNA damage response, and T-cell activation.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Medicinal
Krimo Toutah, Nabanita Nawar, Sanna Timonen, Helena Sorger, Yasir S. Raouf, Shazreh Bukhari, Jana von Jan, Aleksandr Ianevski, Justyna M. Gawel, Olasunkanmi O. Olaoye, Mulu Geletu, Ayah Abdeldayem, Johan Israelian, Tudor B. Radu, Abootaleb Sedighi, Muzaffar N. Bhatti, Muhammad Murtaza Hassan, Pimyupa Manaswiyoungkul, Andrew E. Shouksmith, Heidi A. Neubauer, Elvin D. de Araujo, Tero Aittokallio, Oliver H. Kraemer, Richard Moriggl, Satu Mustjoki, Marco Herling, Patrick T. Gunning
Summary: Epigenetic targeting, especially with HDAC inhibitors like KT-531, has shown promising efficacy in treating hematological cancers. In the case of T-cell prolymphocytic leukemia (T-PLL), overexpression of HDAC6 has been identified as a target for therapy, with KT-531 demonstrating strong inhibitory potency and safety in preclinical studies. Combination studies with approved cancer drugs have shown synergistic effects, indicating the potential for durable remission in T-PLL patients.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Julio Flores-Gonzalez, Lucero A. Ramon-Luing, Ranferi Ocana-Guzman, Ivette Buendia-Roldan, Beda Islas-Munoz, Patricia Volkow-Fernandez, Leslie Chavez-Galan
Summary: This study evaluated the frequency and phenotype of natural killer subpopulation cells in people living with HIV and Kaposi sarcoma, and found that the immune response of the patients was enhanced in those treated with valganciclovir plus antiretroviral therapy.
Article
Medicine, General & Internal
Tarisiro Matiza, Kathryn F. Boyd, Rebecca A. Lyall, Douglas S. Kwon, Alan M. McGregor, Suzanne Fiorillo, Thomas B. Campbell, Margaret Borok, Bjoern Corleis
Summary: The study revealed that T cells in the alveolar space of HIV-1-associated pKS patients exhibit reduced inflammatory capacities and diminished polyfunctionality compared to blood T cells, without increased expression of exhaustion markers. A negative correlation was found between the production of MIP1-beta and TNF-alpha in T cells in BAL and blood, indicating compartmentalized immune responses to pKS and accentuated chronic HIV-1/HHV-8 pathogenesis via T cells in the lungs of people with pKS.
Article
Dermatology
Giuseppe Ingrasci, Julio Diaz-Perez, Sebastian Verne, Paolo Romanelli, Gil Yosipovitch
Summary: T-cell prolymphocytic leukemia (TPLL) is a rare form of leukemia characterized by T lymphocytes at an intermediate stage of development with varied facial involvement. Diagnosis of TPLL involves flow cytometry and histopathology, and dermatologists should be aware of its unique features.
AMERICAN JOURNAL OF DERMATOPATHOLOGY
(2021)
