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Severe Congenital Neutropenia
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
It is now clear that mutations in the genes encoding proteins involved in receptor binding (G-CSFR, CXCR4), endoplasmic reticulum (G6PT, G6PC3, JAGN1, VPS13B), ribosomes (SBDS), nucleus (GF11, GATA2), mitochondria (HAX1, TAZ, AK2), endosomes and lysosomes (AP3B1, LYST, RAB27A), and cytoskeleton (WAS, HAX1), increase endoplasmic reticulum stress and apoptosis, deregulate transcription factors expression, alter granulocyte colony-stimulating factor receptor (G-CSFR) signal transduction, leading to arrest of granulopoiesis and acquisition of second leukemia-associated mutation (e.g., RUNX1) before conversion to MDS and AML (Table 77.1) [3–11].
Overview and recent advances in the targeting of medulloblastoma cancer stem cells
Published in Expert Review of Anticancer Therapy, 2021
In 2015, it was published that cancer cell lines from multiple tumor types, including medulloblastoma, contained subpopulations that demonstrated cell surface expression of the granulocyte colony stimulating factor receptor (GCSF-R, CD114) [106]. CD114 has previously been described as a possible marker of CSCs in neuroblastoma [107], as CD114 expression defined a discrete subpopulation within neuroblastoma cell lines with self-renewal, pluripotency, and enhanced tumorigenicity. This CD114+ cell subpopulation was also distinct from previously characterized tumor-initiating cell subpopulations defined by CD133 expression, neurosphere assays, and side population staining. Further studies using limiting dilution and competitive lineage-tracing assays demonstrated CD114+ cells were capable of both self-renewal and differentiation. The gene expression patterns of CD114+ cells closely resembled embryonic and induced pluripotent stem cells and were similar to premigratory neural crest cells, while the CD114- subpopulation demonstrated gene expression patterns consistent with migratory neural crest cells representing a later stage of differentiation. CD114+ cells also were treatment-resistant, and CD114+ neuroblastoma cells were enriched in post-chemotherapy patient samples, and further increased in post-chemotherapy metastases. Xenograft tumors treated with chemotherapy demonstrated similar increases in the prevalence of CD114+ cells.
New insight into the mechanism of granulocyte colony-stimulating factor (G-CSF) that induces the mobilization of neutrophils
Published in Hematology, 2021
Abdulrahman Theyab, Mohammad Algahtani, Khalaf F. Alsharif, Yousef M. Hawsawi, Abdulaziz Alghamdi, Adel Alghamdi, Jude Akinwale
Effects of G-CSF are mediated by binding to a single homodimer receptor, granulocyte colony stimulating factor receptor (G-CSFR). Therefore, the regulation, proliferation, and differentiation of neutrophils precursors are highly dependent upon binding to their receptors [15]. GCSF-R is a membrane protein expressed in all granulocytic lineage cells, including neutrophils, progenitors, and myeloid leukemia cells [31]. G-CSFRs have also been detected on normal B & T lymphocytes, monocytes [32,33], and non-hematopoietic tissues, such as cardiomyocytes [34], vascular endothelial cells [35], neural stem cells [36], placenta [37], and many non-hematopoietic tumors cell lines [38].G-CSFRs are mainly expressed on common myeloid precursors (CMP), and mature neutrophils, however, the expression of these receptors increases more during maturation [39]. Recently, G-CSFRs have been shown to be highly expressed on human gastric and colon cancer cells [16].