Le Touquet – Paris-Plage, France
Le Touquet – Paris-Plage, France

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Arnaud L.,National Institute of Blood Transfusion | Saison C.,National Institute of Blood Transfusion | Helias V.,National Institute of Blood Transfusion | Lucien N.,National Institute of Blood Transfusion | And 25 more authors.
American Journal of Human Genetics | Year: 2010

The congenital dyserythropoietic anemias (CDAs) are inherited red blood cell disorders whose hallmarks are ineffective erythropoiesis, hemolysis, and morphological abnormalities of erythroblasts in bone marrow. We have identified a missense mutation in KLF1 of patients with a hitherto unclassified CDA. KLF1 is an erythroid transcription factor, and extensive studies in mouse models have shown that it plays a critical role in the expression of globin genes, but also in the expression of a wide spectrum of genes potentially essential for erythropoiesis. The unique features of this CDA confirm the key role of KLF1 during human erythroid differentiation. Furthermore, we show that the mutation has a dominant-negative effect on KLF1 transcriptional activity and unexpectedly abolishes the expression of the water channel AQP1 and the adhesion molecule CD44. Thus, the study of this disease-causing mutation in KLF1 provides further insights into the roles of this transcription factor during erythropoiesis in humans. © 2010 The American Society of Human Genetics. All rights reserved.


Douay L.,University Pierre and Marie Curie | Douay L.,University Paris Est Creteil | Peyrard T.,Sanguine | Peyrard T.,Center National Of Reference Pour Les Groupes Sanguins
Revue Francophone des Laboratoires | Year: 2012

RBCs can be now cultured in vitro from various human stem cells: hematopoïetic, embryonic or induced pluripotent stem cells (hiPSCs). The hiPSC technology represents a potentially unlimited source of RBCs and opens the door to the development of a new generation of allogeneic transfusion products. Assuming that in vitro large-scale cultured RBC production efficiently operates in the near future, we draw here a futuristic, but realistic scenario, regarding potential applications for alloimmunized patients and those with a rare blood group. We show that only 3 hiPSC clones would have been sufficient to match more than 99% of the patients in need of RBC transfusions. In addition, one single hiPSC clone would have met more than 70% of the needs in alloimmunized patients with sickle cell disease. As a whole a very limited number of RBC clones would provide for the need for most alloimmunized patients and those with a rare blood group. © 2012 - Elsevier Masson SAS - Tous droits réserv́s.


Peyrard T.,Sanguine | Bardiaux L.,Center National Of Reference Pour Les Groupes Sanguins | Krause C.,Etablissement Francais du Sang Bourgogne Franche Comte | Kobari L.,French Institute of Health and Medical Research | And 3 more authors.
Transfusion Medicine Reviews | Year: 2011

The transfusion of red blood cells (RBCs) is now considered a well-settled and essential therapy. However, some difficulties and constraints still occur, such as long-term blood product shortage, blood donor population aging, known and yet unknown transfusion-transmitted infectious agents, growing cost of the transfusion supply chain management, and the inescapable blood group polymorphism barrier. Red blood cells can be now cultured in vitro from human hematopoietic, human embryonic, or human-induced pluripotent stem cells (hiPSCs). The highly promising hiPSC technology represents a potentially unlimited source of RBCs and opens the door to the revolutionary development of a new generation of allogeneic transfusion products. Assuming that in vitro large-scale cultured RBC production efficiently operates in the near future, we draw here some futuristic but realistic scenarios regarding potential applications for alloimmunized patients and those with a rare blood group. We retrospectively studied a cohort of 16,486 consecutive alloimmunized patients (10-year period), showing 1 to 7 alloantibodies with 361 different antibody combinations. We showed that only 3 hiPSC clones would be sufficient to match more than 99% of the 16,486 patients in need of RBC transfusions. The study of the French National Registry of People with a Rare Blood Phenotype/Genotype (10-year period) shows that 15 hiPSC clones would cover 100% of the needs in patients of white ancestry. In addition, one single hiPSC clone would meet 73% of the needs in alloimmunized patients with sickle cell disease for whom rare cryopreserved RBC units were required. As a result, we consider that a very limited number of RBC clones would be able to not only provide for the need for most alloimmunized patients and those with a rare blood group but also efficiently allow for a policy for alloimmunization prevention in multiply transfused patients. © 2011 Elsevier Inc.


Monfort M.,University of Liège | Peyrard T.,Center National Of Reference Pour Les Groupes Sanguins | Peyrard T.,Sanguine | Arnaud L.,Sanguine | And 3 more authors.
Transfusion Clinique et Biologique | Year: 2013

The patient's rare KEL:1,-2 phenotype was highlighted in course of a routine preoperative erythrocyte typing. Unexpectedly, her two daughters presented a KEL:-1,2 phenotype what appeared first as an apparent maternity exclusion. Flow cytometry, genotyping and adsorption-elution analyses were then performed for those three patients. KEL genotyping showed that the patient's genotype was KEL*01/KEL*02 whereas that of her daughters was KEL*02/KEL*02. By using polyclonal anti-KEL2 reagent, weak amount of KEL2 was identified on the patient's erythrocytes, a result which was confirmed by both flow cytometry and adsorption-elution assays, suggesting that patient's phenotype was in fact KEL:1,2w. These results are in favour of a weak expressed KEL*02 allele (KEL*2mod) transmission coding for a KEL2 antigen detected in some technical conditions only. Those results allowed to explain the apparent maternity exclusion based on initial KEL phenotype. This study also seems to confirm the presence of a compensatory mechanism of the KELmod allele deficient expression in heterozygote patients. A KEL phenotype retrospective study of 80,000 subjects showed a local KEL:1,-2 frequency four times lower than that described in literature. Moreover, a significant number of those individuals would in reality be KEL:1,2w, what still would decrease the real frequency of the KEL:1,2 subjects. © 2013 Elsevier Masson SAS.

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