IX. GENETICS AND HUMAN HEMOGLOBIN CHEMISTRY 461 



tions; bone marrow is the latest hematopoietic site in fetuses and red 

 cells produced in bone marrow are presumably more differentiated toward 

 the Hb-A containing red cell type. 



Kleihauer et al. (1957) have devised a method to demonstrate 

 Hb-F within single cells, by washing blood smears with buffer solutions, 

 which selectively dissolve Hb-A; the hemoglobin left in the red cells 

 is assumed to be Hb-F. By this method of analysis Kleihauer et al. 

 (1957) have shown that Hb-A and Hb-F are both present in variable 

 ratios in the same red cells. Moreover, under suitable conditions, all the 

 red cells of sickle-cell anemic patients show the sickling phenomenon. 

 Since relatively large amounts of Hb-F may be present in sickle-cell 

 anemia, this prove sthat Hb-S and Hb-F are present together in the 

 same red cells. 



1. The Occurrence of Hb-F in Adults 



Hb-F is present in some adults affected by hereditary or acquired 

 hematological disorders. Hereditary conditions in which Hb-F is con- 

 stantly found in adults include sickle-cell anemia, thalassemia major, 

 and the anemias caused by a thalassemic gene in combination with a 

 gene for an abnomial hemoglobin. Acquired pathological conditions in 

 which Hb-F has occasionally been reported include pernicious anemia, 

 hypoplastic anemia, leukemia, and other types of anemia (Singer et al., 

 1951; Chernoff, 1953; White and Beaven, 1959). 



The level of Hb-F in anemic patients varies over a wide range; the 

 highest levels of Hb-F have been observed in thalassemia major, where 

 Hb-F frequently approaches 90-95% (Rich, 1952). A slight amount of 

 Hb-F has been reported to be present in pregnant women (Rucknagel 

 and Chernoff, 1955) and in women with hydatid moles (Bromberg et al, 

 1957), conditions in which high amounts of chorionic gonadotropin are 

 secreted. These observations suggested that gonadotropin may stimulate 

 Hb-F production (Rucknagel and Chernoff, 1955). 



The appearance of Hb-F in hematological disorders has been con- 

 sidered to be the consequence of severe and chronic anemia or a com- 



FiG. 13. The switch from Hb-F synthe.sis to Hb-A .synthesis. indicates 



the mean relative amount of y peptide chain present during the last months of fetal 



life and the first 10 months after birth; indicates the mean relative amount 



of y8 peptide chain; and the relative amount of a peptide chain during 



the same period. The a peptide chain is con.stantlv 100% since this chain is common 



to Hb-F and Hb-A; = percentages of Hb-F present at birth in relation to 



gestational age (data from Cook et al., 1957). x x x x x = percentages of Hb-F 

 pre.sent in children from 1 to 10 months of age (data from Chernoff and Singer, 

 1952). 



