The latest medical research on Acute Lymphoblastic Leukaemia
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about acute lymphoblastic leukaemia gathered by our medical AI research bot.
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IL-15-secreting CAR natural killer cells directed toward the pan-cancer target CD70 eliminate both cancer cells and cancer-associated fibroblasts.Leukaemia
It remains challenging to obtain positive outcomes with chimeric antigen receptor (CAR)-engineered cell therapies in solid malignancies, like colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC). A major obstacle is the lack of targetable surface antigens that are not shared by healthy tissues. CD70 emerges as interesting target, due to its stringent expression pattern in healthy tissue and its apparent role in tumor progression in a considerable amount of malignancies. Moreover, CD70 is also expressed on cancer-associated fibroblasts (CAFs), another roadblock for treatment efficacy in CRC and PDAC. We explored the therapeutic potential of CD70 as target for CAR natural killer (NK) cell therapy in CRC, PDAC, focusing on tumor cells and CAFs, and lymphoma.
RNA-seq data and immunohistochemical analysis of patient samples were used to explore CD70 expression in CRC and PDAC patients. In addition, CD70-targeting CAR NK cells were developed to assess cytotoxic activity against CD70+ tumor cells and CAFs, and the effect of cytokine stimulation on their efficacy was evaluated. The in vitro functionality of CD70-CAR NK cells was investigated against a panel of tumor and CAF cell lines with varying CD70 expression. Lymphoma-bearing mice were used to validate in vivo potency of CD70-CAR NK cells. Lastly, to consider patient variability, CD70-CAR NK cells were tested on patient-derived organoids containing CAFs.
In this study, we identified CD70 as a target for tumor cells and CAFs in CRC and PDAC patients. Functional evaluation of CD70-directed CAR NK cells indicated that IL-15 stimulation is essential to obtain effective elimination of CD70+ tumor cells and CAFs, and to improve tumor burden and survival of mice bearing CD70+ tumors. Mechanistically, IL-15 stimulation resulted in improved potency of CD70-CAR NK cells by upregulating CAR expression and increasing secretion of pro-inflammatory cytokines, in a mainly autocrine or intracellular manner.
We disclose CD70 as an attractive target both in hematological and solid tumors. IL-15 armored CAR NK cells act as potent effectors to eliminate these CD70+ cells. They can target both tumor cells and CAFs in patients with CRC and PDAC, and potentially other desmoplastic solid tumors.
cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Leukaemia
Cancer is a complex disease resulting from abnormal cell growth that is induced by a number of genetic and environmental factors. The tumor microen...
The Association of Agent Orange Exposure with the progression of monoclonal gammopathy of undetermined significance to multiple myeloma: a population-based study of Vietnam War Era Veterans.Leukaemia
Herbicide and pesticide exposure [e.g., agent orange (AO)] is associated with an increased risk of multiple myeloma (MM) due to the contaminant, 2,...
Vaccines: a promising therapy for myelodysplastic syndrome.Leukaemia
Myelodysplastic neoplasms (MDS) define clonal hematopoietic malignancies characterized by heterogeneous mutational and clinical spectra typically s...
Bone marrow graft versus peripheral blood graft in haploidentical hematopoietic stem cells transplantation: a retrospective analysis in1344 patients of SFGM-TC registry.Leukaemia
The use of peripheral blood (PB) or bone marrow (BM) stem cells graft in haploidentical hematopoietic stem cell transplantation with post-transplan...
The promise and challenges of combination therapies with antibody-drug conjugates in solid tumors.Leukaemia
Antibody-drug conjugates (ADCs) represent an important class of cancer therapies that have revolutionized the treatment paradigm of solid tumors. T...
Phase separations in oncogenesis, tumor progressions and metastasis: a glance from hallmarks of cancer.Leukaemia
Liquid-liquid phase separation (LLPS) is a novel principle for interpreting precise spatiotemporal coordination in living cells through biomolecula...
Integrative analysis of clinicopathological features defines novel prognostic models for mantle cell lymphoma in the immunochemotherapy era: a report from The North American Mantle Cell Lymphoma Consortium.Leukaemia
Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes.
The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed between 2000 and 2012 are included in this study. A comprehensive retrospective analysis was performed on the clinicopathological features, treatment approaches, and outcomes of these cases. The establishment of novel prognostic models was based on in-depth examination of baseline parameters, and subsequent validation in an independent cohort of MCL cases.
In front-line strategies, the use of hematopoietic stem cell transplantation was the most significant parameter affecting outcomes, for both overall survival (OS, p < 0.0001) and progression-free survival (PFS, p < 0.0001). P53 positive expression was the most significant pathological parameter correlating with inferior outcomes (p < 0.0001 for OS and p = 0.0021 for PFS). Based on the baseline risk factor profile, we developed a set of prognostic models incorporating clinical, laboratory, and pathological parameters that are specifically tailored for various applications. These models, when tested in the validation cohort, exhibited strong predictive power for survival and showed a stratification resembling the training cohort.
The outcome of patients with MCL has markedly improved over the past two decades, and further enhancement is anticipated with the evolution of clinical management. The innovative prognostic models developed in this study would serve as a valuable tool to guide the selection of more suitable treatment strategies for patients with MCL.
Harnessing immunotherapy for brain metastases: insights into tumor-brain microenvironment interactions and emerging treatment modalities.Leukaemia
Brain metastases signify a deleterious milestone in the progression of several advanced cancers, predominantly originating from lung, breast and me...
Multiscale protein networks systematically identify aberrant protein interactions and oncogenic regulators in seven cancer types.Leukaemia
Global proteomic data generated by advanced mass spectrometry (MS) technologies can help bridge the gap between genome/transcriptome and functions ...
Safety and antitumor activity of metformin plus lanreotide in patients with advanced gastro-intestinal or lung neuroendocrine tumors: the phase Ib trial MetNET2.Leukaemia
In retrospective studies, metformin use has been associated with better clinical outcomes in diabetic patients with advanced, well-differentiated n...
Considerations for the design of antibody drug conjugates (ADCs) for clinical development: lessons learned.Leukaemia
Antibody-drug conjugates (ADCs) have emerged as a novel therapeutic strategy that has successfully reached patient treatment in different clinical ...