Increased Fanconi C expression contributes to the emergency granulopoiesis response

Hu, Liping; Huang, Weiqi; Hjort, Elizabeth; Eklund, Elizabeth A.

doi:10.1172/jci69032

Cited by 30 publications

(112 citation statements)

References 50 publications

Supporting

Mentioning

103

Contrasting

Order By: Relevance

“…Cells from the two femora were combined and counted for each individual mouse. This technique was highly reproducible in our laboratory (12,17,22). In some studies, CD34…”

Section: Studies Of Murine Bone Marrow and Othermentioning

confidence: 91%

“…Emergency granulopoiesis is studied in mice by intraperitoneal injection of either pathogens (bacterial/fungal) or an ovalbumin/alum mixture (referred to as Alum) (9,10,12,38). In either model, mice develop an IL1␤-dependent response that includes immediate release of granulocytes from the bone marrow, increased G-CSF in the serum and bone marrow, increased granulopoiesis, and circulating granulocytosis (maximal at 10 -14 days) (9,12,38).…”

Section: Icsbpmentioning

confidence: 99%

“…In either model, mice develop an IL1␤-dependent response that includes immediate release of granulocytes from the bone marrow, increased G-CSF in the serum and bone marrow, increased granulopoiesis, and circulating granulocytosis (maximal at 10 -14 days) (9,12,38). Because we were interested in studying multiple episodes of emergency granulopoiesis, we chose an Alum injection because it does not result in death or chronic infection in WT mice.…”

Section: Icsbpmentioning

confidence: 99%

“…Granulocyte release is dependent on CXCR proteins and their ligands (11). S phase shortening during progenitor expansion requires activation of the Fanconi DNA repair pathway to maintain genomic integrity (12). Also, both expansion and differentiation of progenitors require the transcription factors Stat3 and C/EBP␤ (7,8).…”

mentioning

confidence: 99%

“…Neurofibromin1, Bcl2, and Klf4), and co-regulators of Fas and ␤catenin (e.g. Fap1 and Gas2) (12,18,21,22,25,29).…”

mentioning

confidence: 99%

See 4 more Smart Citations

The Interferon Consensus Sequence Binding Protein (Icsbp/Irf8) Is Required for Termination of Emergency Granulopoiesis

Hu¹,

Huang

Hjort³

et al. 2016

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Emergency granulopoiesis occurs in response to infectious or inflammatory challenge and is a component of the innate immune response. Some molecular events involved in initiating emergency granulopoiesis are known, but termination of this process is less well defined. In this study, we found that the interferon consensus sequence binding protein (Icsbp/Irf8) was required to terminate emergency granulopoiesis. Icsbp is an interferon regulatory transcription factor with leukemia suppressor activity. Expression of Icsbp is decreased in chronic myeloid leukemia, and Icsbp ؊/؊ mice exhibit progressive granulocytosis with evolution to blast crisis, similar to the course of human chronic myeloid leukemia. In this study, we found aberrantly sustained granulocyte production in Icsbp ؊/؊ mice after stimulation of an emergency granulopoiesis response. Icsbp represses transcription of the genes encoding Fas-associated phosphatase 1 (Fap1) and growth arrest-specific 2 (Gas2) and activates genes encoding Fanconi C and F. After stimulation of emergency granulopoiesis, we found increased and sustained expression of Fap1 and Gas2 in bone marrow myeloid progenitor cells from Icsbp ؊/؊ mice in comparison with the wild type.This was associated with resistance to Fas-induced apoptosis and increased ␤-catenin activity in these cells. We also found that repeated episodes of emergency granulopoiesis accelerated progression to acute myeloid leukemia in Icsbp ؊/؊ mice. This was associated with impaired Fanconi C and F expression and increased sensitivity to DNA damage in bone marrow myeloid progenitors. Our results suggest that impaired Icsbp expression enhances leukemogenesis by deregulating processes that normally limit granulocyte expansion during the innate immune response.

show abstract

“…Cells from the two femora were combined and counted for each individual mouse. This technique was highly reproducible in our laboratory (12,17,22). In some studies, CD34…”

Section: Studies Of Murine Bone Marrow and Othermentioning

confidence: 91%

Section: Icsbpmentioning

confidence: 99%

Section: Icsbpmentioning

confidence: 99%

mentioning

confidence: 99%

“…Neurofibromin1, Bcl2, and Klf4), and co-regulators of Fas and ␤catenin (e.g. Fap1 and Gas2) (12,18,21,22,25,29).…”

mentioning

confidence: 99%

See 3 more Smart Citations

The Interferon Consensus Sequence Binding Protein (Icsbp/Irf8) Is Required for Termination of Emergency Granulopoiesis

Hu¹,

Huang

Hjort³

et al. 2016

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

Why hematopoietic stem cells fail in Fanconi anemia: Mechanisms and models

Liu,

Vivona,

Kurre

2024

BioEssays

View full text Add to dashboard Cite

Fanconi anemia (FA) is generally classified as a DNA repair disorder, conferring a genetic predisposition to cancer and prominent bone marrow failure (BMF) in early childhood. Corroborative human and murine studies point to a fetal origin of hematopoietic stem cell (HSC) attrition under replicative stress. Along with intriguing recent insights into non‐canonical roles and domain‐specific functions of FA proteins, these studies have raised the possibility of a DNA repair‐independent BMF etiology. However, deeper mechanistic insight is critical as current curative options of allogeneic stem cell transplantation and emerging gene therapy have limited eligibility, carry significant side effects, and involve complex procedures restricted to resource‐rich environments. To develop rational and broadly accessible therapies for FA patients, the field will need more faithful disease models that overcome the scarcity of patient samples, leverage technological advances, and adopt investigational clinical trial designs tailored for rare diseases.

show abstract

Impaired immune response to Candida albicans in cells from Fanconi anemia patients

Parodi¹,

Kalli²,

Svahn

et al. 2015

Cytokine

View full text Add to dashboard Cite

Increased Fanconi C expression contributes to the emergency granulopoiesis response

Cited by 30 publications

References 50 publications

The Interferon Consensus Sequence Binding Protein (Icsbp/Irf8) Is Required for Termination of Emergency Granulopoiesis

The Interferon Consensus Sequence Binding Protein (Icsbp/Irf8) Is Required for Termination of Emergency Granulopoiesis

Why hematopoietic stem cells fail in Fanconi anemia: Mechanisms and models

Impaired immune response to Candida albicans in cells from Fanconi anemia patients

Contact Info

Product

Resources

About