المؤلفون: Joseph T. Opferman, Brittany J. Kartchner, Peter Vogel, Kaitlyn H. Smith, Meghan E. Turnis, Ewa Kaminska, Richard A. Ashmun, Paul A. Ney, Jonathan D. Laxton

المصدر: Blood

مصطلحات موضوعية: 0301 basic medicine, Male, Erythrocytes, Immunology, bcl-X Protein, Apoptosis, Biology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Red Cells, Iron, and Erythropoiesis, Downregulation and upregulation, Erythroid Cells, hemic and lymphatic diseases, Animals, Humans, MCL1, Erythropoiesis, Cells, Cultured, Effector, Siblings, Gene Expression Regulation, Developmental, Embryo, Anemia, Cell Biology, Hematology, Embryonic stem cell, Cell biology, Mice, Inbred C57BL, 030104 developmental biology, Proto-Oncogene Proteins c-bcl-2, 030220 oncology & carcinogenesis, Embryo Loss, Myeloid Cell Leukemia Sequence 1 Protein, Ectopic expression, Gene Deletion

الوصف: Although BCL-xL is critical to the survival of mature erythrocytes, it is still unclear whether other antiapoptotic molecules mediate survival during earlier stages of erythropoiesis. Here, we demonstrate that erythroid-specific Mcl1 deletion results in embryonic lethality beyond embryonic day 13.5 as a result of severe anemia caused by a lack of mature red blood cells (RBCs). Mcl1-deleted embryos exhibit stunted growth, ischemic necrosis, and decreased RBCs in the blood. Furthermore, we demonstrate that MCL-1 is only required during early definitive erythropoiesis; during later stages, developing erythrocytes become MCL-1 independent and upregulate the expression of BCL-xL. Functionally, MCL-1 relies upon its ability to prevent apoptosis to promote erythroid development because codeletion of the proapoptotic effectors Bax and Bak can overcome the requirement for MCL-1 expression. Furthermore, ectopic expression of human BCL2 in erythroid progenitors can compensate for Mcl1 deletion, indicating redundancy between these 2 antiapoptotic family members. These data clearly demonstrate a requirement for MCL-1 in promoting survival of early erythroid progenitors.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::74ce0aad529c38194aee9aa6dac471d5Test
https://pubmed.ncbi.nlm.nih.gov/33830190Test

المؤلفون: Paul A. Ney

المصدر: Blood. 118:6728-6729

مصطلحات موضوعية: Cyclopentenone, Immunology, Prostaglandin, Cell Biology, Hematology, Friend Murine Leukemia Virus, Leukemic Hematopoietic Stem Cell, medicine.disease, Biochemistry, Eicosapentaenoic acid, chemistry.chemical_compound, Leukemia, chemistry, Apoptosis, Cancer research, medicine, Stem cell

الوصف: In this issue of Blood , Hegde et al show that a novel and naturally produced eicosapentaenoic acid–derived cyclopentenone prostaglandin has antileukemic activity.[1][1] Δ12-PGJ3–mediated apoptosis of leukemic stem cells is mediated at least in part by ATM-p53 signaling. ![Figure][2]

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::a9d31de911e35f0ef84d20ccd3d2f811Test
https://doi.org/10.1182/blood-2011-10-385328Test