0000000000539135
AUTHOR
Julien Rossignol
showing 3 related works from this author
Efficacy of Azacitidine (AZA) in Autoimmune and Inflammatory Disorders (AID) Associated with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocyt…
2015
Abstract Background: AID are seen in 10-30% of MDS and CMML. After initial response to steroids, AID are often poorly controlled and steroid-sparing drugs are difficult to use due to the underlying MDS/CMML. Some case reports suggest a beneficial role of AZA treatment in AID associated to MDS/CMML. Methods: We retrospectively analyzed 22 MDS/CMML patients (pts) with AID who received AZA in French centers between January 2007 and May 2014. Results: Median age of the 22 pts was 70y (range 41-84), including 6F/16M. Diagnosis of MDS/CMML preceded AID (n=8) by a median of 17 months (mo), was concomitant with (n=7) or followed AID (n=7) by a median of 20 mo. 14 pts had lower risk IPSS and 8 highe…
XPO1 (Exportin-1) Is a Major Regulator of Human Erythroid Differentiation. Potential Clinical Applications to Decrease Ineffective Erythropoiesis of …
2015
Abstract Background We and others have shown that normal human erythroid cell maturation requires a transient activation of caspase-3 at late stages of maturation (Zermati et al, J Exp Med 2001). We further documented that, in human erythroblasts, the chaperone HSP70 is constitutively expressed and, at late stages of maturation, translocates into the nucleus and protects GATA-1, the master transcriptional factor critical for erythropoiesis, from caspase-3 cleavage (Ribeil et al, Nature 2007). During the maturation of human β-TM erythroblasts, HSP70 is sequestrated by excess of α-globin chains in the cytoplasm and as a consequence, GATA-1 is no longer protected from caspase-3 cleavage result…
XPO1 regulates erythroid differentiation and is a new target for the treatment of β-thalassemia
2019
β-thalassemia major (β-TM) is an inherited hemoglobinopathy caused by a quantitative defect in the synthesis of β-globin chains of hemoglobin, leading to the accumulation of free a-globin chains that aggregate and cause ineffective erythropoiesis. We have previously demonstrated that terminal erythroid maturation requires a transient activation of caspase-3 and that the chaperone Heat Shock Protein 70 (HSP70) accumulates in the nucleus to protect GATA-1 transcription factor from caspase-3 cleavage. This nuclear accumulation of HSP70 is inhibited in human β-TM erythroblasts due to HSP70 sequestration in the cytoplasm by free a-globin chains, resulting in maturation arrest and apoptosis. Like…