Changing erythrocyte populations in juvenile chronic myelocytic leukemia: evidence for disordered regulation

Abstract

Fetal and adult erythrocyte characteristics were studied serially in a 30-mo-old female with juvenile chronic myelocytic leukemia. On presentation the erythrocytes exhibited predominantly fetal characteristics as indicated by 69% hemoglobin F (HbF), 1.1% hemoglobin A2 (HbA2), absent I antigen, and fetal levels of the erythrocyte enzymes, carbonic anhydrase I and II, glucose-6-phosphate dehydrogenase, hexokinase, pyruvate kinase, and lactate dehydrogenase; 100% of the erythrocytes present contained HbF. However, Orskov-Jacobs- Stewart hemolysis demonstrated that at least one adult characteristic was present. Seven months later HbF was 17%; I antigen and carbonic anhydrase I had increased to adult levels. The number of cells containing HbF had decreased to 30%. Further studies indicated that at least three new populations of red cells were present after 7 mo which had not previously been detected. Two of these populations exhibited a mixture of both fetal and adult characteristics. Such findings suggested that an ongoing disturbance of regulatory mechanisms was responsible for the variable expression of fetal versus adult erythrocyte characteristics.

Genetic Relationship between Fetal Hb Levels in Normal and Erythropoietically Stressed Baboons

“…Whether these findings can be reproduced in man remains to be determined, but there is evidence suggesting that both increased F-cell numbers and age dependent increased Hb F pcr F-cell occur in certain clinical situations. Increase in F-cells has been demonstrated in congenital hypoplastic anaemias (Alter, 1979) and during the recovery from transient erythroid hypoplasia (Sheridan et al, 1976;Alter, 1979), after phlebotomy (Papayannopoulou et a/, 1980), and an increase in the concentration of Hb F per cell was found in chronic juvenile myeloid leukaemia (Dover et a!, 1977). In patients with sickle cell anaemia the number of F-cells is increased, but in most cases the corpuscular concentration of Hb F is not high enough to inhibit sickling.…”

Isozyme patterns in erythrocytes from human fetuses

“…This has been best studied in patients with the juvenile form of chronic myelogenous leukemia, where there is a reversion from adult to fetal phenotype in hemoglobin (from Hb A to Hb F), carbonic anhydrase activity (decrease), and amount ofi. antigen on the cell surface (increase) [16][17][18][19][20] . The combined appearance of these fetal red cell characteristics have been attributed to a malignant proliferation of a "fetal" hemopoietic stem cell [16,21].…”

Characterization of the erythropoietic precursors (BFU‐E) in a patient with juvenile chronic myelogenous leukaemia by the analysis of Gγ and Aγ globin chains

“…J-CML differs in several features from adult type of CML. In particular, the high Hb F level (Hardisty et al, 1964;Weatherall et al, 1968) and the high frequency occurrence of F-cells (Dover et al, 1977) are well known. Our present observations show that all bursts are heterogenously committed to y chain synthesis but did not reveal discontinuous populations committed to synthesis of y or p chains and the distribution of y chain synthesis approached a normal distribution.…”

“…anhydrase activity (Hardisty et al 1964: Weatherall et al, 1968: Cao. 1976: Gahr etal, 1976Weatherall & Brown, 1970) and decreased titre of I antigen (Dover et al, 1977;Weatherall et al 1968). Altman et d ( 1 9 7 4 ) and Suda et al(1982) demonstrated that the growth patterns of granulocyte-macrophage colony forming cells in J-CML revealed a predominance of macrophage colonies (M-CFC).…”

“…Juvenile chronic myelogenous leukaemia (J-CML) differs in several features from the adult type of CML: lack of response to chemotherapy, the absence of the Ph' chromosome and a much more rapid and aggressive course. In addition, it is well known that it manifests certain similarities to fetal type haemopoiesis including high levels of fetal haemoglobin (Hb F) (Hardisty et al, 1964), an increase in the number of F-cells (Dover et al, 1977), a subnormal level of haemoglobin A2 (Hardisty et af, 1964;Weatherall et aI, 19681, increased glucose 6-phosphate dehydrogenase activity (Cao, 1976;Gahr et al, 1976), reduced carbonic Correspondence: Dr Takashi Terasawa, Department of Physiology, Tohoku Dental University, 3 1-1 Mitsumido, Tomitamachi, Koriyamashi. Fukushimaken 963, Japan.…”