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01-09-2019 | Myelodysplastic Syndrome | Original Article

BOK promotes erythropoiesis in a mouse model of myelodysplastic syndrome

Authors: Seong-Ho Kang, Oscar Perales, Michael Michaud, Samuel G. Katz

Published in: Annals of Hematology | Issue 9/2019

Abstract

Myelodysplastic syndromes are clonal hematopoietic stem cell disorders characterized by cytopenia and intramedullary apoptosis. BCL-2 Ovarian Killer (BOK) is a pro-apoptotic member of the BCL-2 family of proteins which, when stabilized from endoplasmic reticulum-associated degradation (ERAD), induces apoptosis in response to ER stress. Although ER stress appropriately activates the unfolded protein response (UPR) in BOK-disrupted cells, the downstream effector signaling that includes ATF4 is defective. We used Nup98-HoxD13 (NHD13) transgenic mice to evaluate the consequences of BOK loss on hematopoiesis and leukemogenesis. Acute myeloid leukemia developed in 36.7% of NHD13 mice with a Bok gene knockout between the age of 8 and 13 months and presented a similar overall survival to the NHD13 mice. The loss of BOK exacerbated anemia in NHD13 mice, and NHD13/BOK-deficient mice exhibited significantly lower hemoglobin, lower mean cell hemoglobin concentration, and higher mean cell volume than NHD13 mice. Hematopoietic progenitor cell assays revealed a decreased amount of erythroid progenitor stem cells (BFU-E) in the bone marrow of NHD13-transgenic/BOK-deficient mice. RT-qPCR analysis demonstrated decreased mean value of ATF4 in the erythroid progenitors of NHD13 and NHD13/BOK-deficient mice. Our results suggest that in addition to induction of apoptosis in response to ER stress, BOK may regulate erythropoiesis when certain erythroid progenitors experience cell stress.

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Title: BOK promotes erythropoiesis in a mouse model of myelodysplastic syndrome
Authors: Seong-Ho Kang
Oscar Perales
Michael Michaud
Samuel G. Katz
Publication date: 01-09-2019
Publisher: Springer Berlin Heidelberg
Keywords: Myelodysplastic Syndrome
Acute Myeloid Leukemia
Published in: Annals of Hematology / Issue 9/2019
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-019-03726-7

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