In this episode, Carrie-Lynn Grazette, who was diagnosed with acute myeloid leukaemia at the age of 11, relates her story about living with her illness and the Foundation that bears her name.

CARRIE LYNN'S STORY

BEGINNERS GUIDE ON ACUTE MYELOID LEUKEMIA: Ultimate Guide on the Causes and Symptoms of Acute Myeloid Leukemia and a way forward

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Acute myeloid leukemiaAcute myeloid leukemia (AML), additionally called acute myelogenous leukemia, acute myeloblastic leukemia, acute granulocytic leukemia, or acute non-lymphocytic leukemia, is a fast-developing form of most cancers of the blood and bone marrow.AML is the most common form of acute leukemia. It takes place whilst the bone marrow starts to evolve to make blasts, cells which have now completely matured but no longer proliferated. These blasts commonly become white blood cells. However, in AML, these cells no longer spread and are unable to repel infections.In AML, the bone marrow may additionally make odd crimson blood cells and platelets. The quantity of those odd cells will increase hastily, and the odd (leukemia) cells will start to crowd out the regular white blood cells, cri

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BUFFALO, NY- October 30, 2023 – A new editorial paper was published in Oncotarget's Volume 14 on March 24, 2023, entitled, “Neutrophil PAD4: how does it function in cancer beyond promoting NETosis?”

Expansion of pathologically activated immune suppressive myeloid cells called myeloid-derived suppressor cells (MDSC) is one of the hallmarks of cancer. In most tumor types, MDSC are represented primarily by pathologically activated neutrophils (PMN-MDSC). In this new editorial, researchers Laura Garcia-Gerique and Yulia Nefedova from the Wistar Institute discussed their team’s recent study identifying a novel mechanism by which neutrophil PAD4 promotes cancer progression. 

“Using several transplantable and genetically engineered mouse models, we demonstrated that tumor growth was accompanied by significantly elevated enzymatic activity of neutrophil PAD4 [10]. To further clarify the role of PAD4 in tumor progression, we utilized PAD4fl/fl MRP8Cre mice with targeted deletion of PAD4 in myeloid cells, primarily neutrophils.”

PMN-MDSC originate in the bone marrow and migrate to various sites including tumor tissues and premetastatic niches. These cells have a relatively short lifespan (less than 48 hours) and, therefore, are continually replaced from the bone marrow. Tumor-infiltrating PMN-MDSC possess a potent suppressive activity as they are able to inhibit both antigen-specific immune responses of T cells and non-specific anti-CD3/CD28-stimulated responses. As a result, a highly immunosuppressive environment is created in tumors, which prevents their rejection via immunological mechanisms. 

In addition, PMN-MDSC employ non-immunological mechanisms to facilitate tumor progression, including angiogenesis, remodeling of extracellular matrix, and production of cytokines. In patients with solid tumors, levels of MDSC in circulation and tumor tissues have been positively associated with a poor response to the therapy in many types of cancer and represent an independent indicator of poor outcomes. However, many of the details about how PMN-MDSC support cancer progression, and thus approaches for therapeutically targeting these cells, remain enigmatic.

“Taken together, our study identified a new mechanism responsible for transcriptional regulation of neutrophil migration and a new mechanism by which neutrophil PAD4 is contributing to tumor progression. PAD4 inhibitors are in development and may enter early phase clinical trials in the future.”

DOI - https://doi.org/10.18632/oncotarget.28369

Correspondence to - Yulia Nefedova - ynefedova@wistar.org

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Keywords - cancer, PAD4, PMN-MDSC, neutrophils, neutrophil migration

About Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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Neutrophil PAD4 in Cancer, Beyond Promoting NETosis

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Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

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