Characterization of the erythropoietic precursors (BFU-E) in a patient with juvenile chronic myelogenous leukaemia by the analysis of G gamma and A gamma globin chains.
In order to investigate the pathogenesis of juvenile chronic myelogenous leukaemia (J-CML) we examined the biosynthetic rates of G gamma and A gamma globin chains in the erythropoietic bursts from the bone marrow of a patient with J-CML. Globin chains were labelled with 14C-labelled amino acids, separated by isoelectric focusing and quantitated by fluorography. The synthesis of gamma-chains in the erythropoietic bursts comprised 89.0% of the total non-alpha-chains. The G gamma:A gamma ratio was 0.67, which is within the ratios obtained in newborns. Furthermore, individual erythropoietic bursts contained varying ratios of both gamma and beta chains and all revealed more G gamma than A gamma chain synthesis. The relative proportions of G gamma and total gamma chain biosynthesis in 62 separate erythropoietic bursts were 0.69 +/- 0.06 and 0.86 +/- 0.06, respectively. Cumulative frequency distributions of individual bursts differing in the ratios of gamma/(gamma + beta) and G gamma/(G gamma + A gamma) approached normal frequency distributions. These results suggest that the levels of Hb F in J-CML are controlled by qualitative changes in a single population of erythropoietic precursors, in which normal switching of the G gamma:A gamma ratio has not occurred, rather than by the abnormal proliferation of an F-cell clone.
D001853:Bone Marrow / Q000378:metabolism; D002478:Cells, Cultured; D004920:Erythropoiesis; D005260:Female; D005914:Globins / Q000096:biosynthesis*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000378:metabolism*
D005914:Globins