Hémoglobine fœtale et hémopathies acquises

Abstract

Though the human γ chain of haemoglobin has appeared initially to be a definite chemical compound, Schroeder et al. showed that at least two and possibly four γ chain loci are active in human newborn. These genes control the synthesis of two different types of γ chains, the G γ and the A γ chains, which differ at least in the position 136 where glycine is replaced by alanine. So, there are two different fœtal haemoglobins which are not separable by chromatography or electrophoresis. Their levels are obtained from the ratio of glycine and alanine at the 136th residue which is included in the third and last peptide obtained by bromide cyanogen (BrCN) hydrolysis of the γ chain : the γCB3 peptide. Schroeder et al. studied the variations of the level of these two chains during the normal ontogenic development and in several cases of hereditary persistance of fœtal haemoglobin (HPFH) and β thalassemias. In this work we studied the γ chains synthetized in different types of anemia, apparently acquired with elevated level of fœtal haemoglobin, where the haemoglobin F level was included between 1 and 15 p. cent, such as refractory anaemias with excess of myeloblasts (RAEM), acquired sideroblastic idiopathic anaemias (ASIA), idiopathic aplastic anaemias, and some varieties of leukemias, especially juvenile myeloid leukemias (JML). We used the method described by Schroeder with slight modifications since our samples were relatively poor in F haemoglobin. After chromatography on Amberlite Biorex 70, the A IC haemoglobin F haemoglobin mixture was fractionated by starch maize block electrophoresis, which is a very efficient method to separate a F/A IC mixture. Then, we used Biogel P10 instead of P100 for the separation of the BrCN peptides, since it seemed to us more appropriate for isolation of the thirteen amino-acids γ CB3 peptide. With this technic, we examined the γ chains of two normal cord blood, of two very young embryos blood and of eleven patients. All of them where presumed to have an acquired high level of fœtal haemoglobin except one case, which was known as an HPFH case and shows the 0.4, 0.6 level of G γ chain described by Schroeder in one category of negro cases. The level of G γ and A γ chains of the cord blood tested are identical to the results found by Schroeder. The G γ /A γ ratio of the embryos are identical to those of the full term fœtuses. Since the embryos were respectively twelve and sixteen weeks old it would prove that the A γ gene is not repressed in the very early time of the fœtal development. The majority of the studied pathological cases (7 out of 10) showed a G γ /A γ ratio very close to 0.80 which is a ratio of the « fœtaltype. The other cases had a ratio between 0.50 and 0.65 which is a ratio observed in the normal adults. Among the « fœtaltype cases, one case must be extracted because the high level of its fœtal haemoglobin is probably not due to its PK deficiency, but seems to be due to an unobserved type of caucasian HPFH. The Kleihauer technic showed in all our cases an heterogeneously distributed F haemoglobin except in the HPFH cases, and no difference was noted between the different other cases. The proportion of G γ and A γ chains in our patients seems to be uncorrelated with the nature of the disease, the level of the haemoglobin synthesized, the state of the bone marrow or the nature of the treatment. There is perhaps some correlation between the level of the total haemoglobin and the nature of the γ chain synthesized, since in the cases with an « adulttype, the anaemia was very recent, at the time of the blood sampling and due to an acute haemolytic crisis. These results clearly show that like in β thalassemias and HPFH, the nature of the γ chain synthesized in the acquired diseases is varying according to the cases. The synthesis of high level A γ chain in some cases of acquired high level of F haemoglobin indicates that the fœtal/adult switch-over of haemoglobin synthesis is more complicated that it has been described until now. It will be interesting to follow the level of the different γ chains according to the genetic or non genetic level of this mechanism.