The patterns of fetal haemoglobin production in leukaemia.
Elevated levels of haemoglobin F (Hb F) have been foudn in a wide range of haematological malignancies, but very high levels were found only in juvenile chronic myeloid leukaemia (JCML), and erythroleukaemia occurring in infancy. In both these disorders a reversion to a fetal form of erythropoiesis may occur, as judged by both the structure of the Hb F and by the disappearance of Hb A2 and the carbnoic-anhydrase isozymes during the course of the illness. The clinical picture of JCML is not always associated with a reversion to fetal erythropoiesis; there appears to be a heterogeneity of conditions with this clinical label. Thus the reversion to a completely fetal pattern of erythropoiesis seems to occur in a variety of leukaemias which start in early life. This change is associated with a uniformly bad prognosis. Of a group of 17 patients with acute myeloid leukaemia 15 developed an increase in the level of Hb F about 60 days after the commencement of treatment; significantly greater increases were observed in those achieving a clinical remission. The level of Hb F usually declined during remission but high levels persisted in a few cases. Increased levels of Hb F were found also in patients with other haematological malignancies who had undergone periods of marrow aplasia during treatment. In all cases the Hb F was heterogeneously distributed throughout the red cells. Analysis of gamma15 or gammaCB3 peptides of Hb F from a variety of leukaemias gave glycine compositions ranging from 0.20 to 0.85 residues with many values in the fetal range; all cases with a reversion to fetal erythropoiesis had values in the fetal range. Attempts to confirm the 'fetal' origin of the cells containing Hb F by means of other markers was possible only in the cases of JCML and in one child with erythroleukaemia. These studies indicate that in some forms of leukaemia there may be a genuine reversion to fetal erythropoiesis while in others the emergence of cells containing Hb F appears to be part of a rapid regeneration process occurring after a period of marrow aplasia. The diagnostic and prognostic value of these observations is discussed.
D000328:Adult; D002256:Carbonic Anhydrases / Q000097:blood; D002675:Child, Preschool; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007048:I Blood-Group System; D007223:Infant; D004915:Leukemia, Erythroblastic, Acute / Q000097:blood; D007945:Leukemia, Lymphoid / Q000097:blood; D007951:Leukemia, Myeloid / Q000097:blood / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000097:blood; D008297:Male
D007048:I Blood-Group System; D005319:Fetal Hemoglobin; D002256:Carbonic Anhydrases