Erythroid Precursors in Congenital Hypoplastic (Diamond-Blackfan) Anemia

Abstract

A B S T R A C T To explore the etiology of congenital hypoplastic anemia (CHA) or the Diamond-Blackfan anemia, erythropoietin responsive committed erythroid precursors were enumerated by the plasma clot method. These included blood and marrow erythroid burst-forming units (BFU-E) and marrow erythroid colony-forming units (CFU-E). The peripheral blood nucleated cells of 11 patients and the marrow cells of seven of these patients were examined. Studies were repeated in several patients during relapse and after induction of remission. BFU-E were undetectable in the marrow and blood of all but one relapsed patient, and the numbers of marrow CFU-E were depressed in all relapsed patients. Blood BFU-E remained low in all of the patients in remission. No evidence was obtained for suppression of normal CFU-E or BFU-E by CHA lymphocytes. Erythropoietin dose-response curves performed in two patients revealed a 10-fold increase in erythropoietin requirement for marrow CFU-E colony growth. This marked unresponsiveness to erythropoietin was strikingly improved by steroid therapy in one patient. We suggest that CHA is the result of a qualitative and/or quantitative deficiency of BFU-E. If BFU-E are produced, they must be relatively unresponsive to erythropoietin. The abnormal BFU-E give rise to erythropoietin unresponsive CFU-E and, thence, to proerythroblasts that are, in turn, trapped in that early stage of development because of their poor erythropoietic response. Hence, red cell production is deficient. Steroids appear to improve the erythropoietin response of CHA erythroid precursors.Dr. Alter is the recipient of U. S.

Ribosomal Protein S19 Deficiency Leads to Reduced Proliferation and Increased Apoptosis but Does Not Affect Terminal Erythroid Differentiation in a Cell Line Model of Diamond-Blackfan Anemia

“…Most cases are sporadic, although in 10%-25% of patients, a positive family history has been described [5,6]. In vitro progenitor culture studies indicate that DBA results from an intrinsic defect in progenitors predominantly affecting erythroid differentiation [7]. Approximately 25% and 2% of the patients have mutations in the genes encoding ribosomal proteins S19 (RPS19) and S24 (RPS24), respectively [8 -10].…”

Anesthetic Management of an Adolescent With Diamond-Blackfan Syndrome During Posterior Spinal Fusion

“…DBA is a congenital red cell hypoplasia first described by Diamond and Blackfan in 1938 [1,2]. The disease usually presents within the first year of life as an anemia with mild macrocytosis, a low reticulocyte count indicative of bone marrow failure, and the near absence of erythroid precursors in the bone marrow.…”

“…Diamond-Blackfan anemia (DBA) was originally described in 1936 by Josephs and was further categorized as a congenital hypoplastic anemia by Diamond and Blackfan in 1938 [1,2]. DBA has also been previously known as congenital hypoplastic anemia, Aase syndrome, and Aase-Smith syndrome II.…”

Anémie de Diamond-Blackfan

“…La possibilité de résolution spontanée, permettant d'arrêter le traitement, sans que l'on puisse en prédire le moment ou la durée, rend néanmoins difficile l'indication 1 , c'est-à-dire au moment où s'exprime une dépendance à l'érythropoïétine [8]. Néanmoins, cette question reste discutée : d'autres travaux ont fait le constat d'une réduction du nombre de progéniteurs précoces BFU-e, ce qui suggère un défaut plus en amont dans la hiérarchie de l'hématopoïèse [9,10]. En accord avec cette idée, il a été montré que la différenciation d'autres lignages hématopoïétiques pouvait être affectée chez certains patients [11,12].…”

“…La cartographie pangénomique des SNP (single nucleotide polymorphisms) réalisée dans 215 familles a révélé d'autres locus en lien avec l'ADB : une région de 18 Mb sur le chromosome 8 (8p23. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] et des régions plus petites sur les chromosomes 6 et 10. Concernant le chromosome 10, le séquençage du gène codant la protéine ribosomique RPS24 a mis en évidence chez trois patients deux mutations non-sens et une délétion de la région codante, absentes lors de l'analyse de 200 génomes contrôles [15].…”