FREE AMINO ACIDS IN BLOOD. II 387 
we have observed that these cells reflect plasma changes in dog myeloid leukemia. 
The relationship between plasma amino acids and platelet and leukocyte amino 
acids has not been studied by other investigators. Our findings indicate that both 
leukocytes and platelets tend to have higher free amino acid pools when they are 
obtained from plasma with higher free amino acid levels. This suggests that these 
cells have the ability to concentrate certain amino acids. The fact that myeloid cells 
do not appear to metabolize free amino acids rapidly on standing 7” vitro (see part I) 
suggests that the free amino acid pool of the leukocyte may be an accurate reflection 
of the ability of these cells to concentrate amino acids such as leucine, isoleucine, 
valine, and other amino acids that are not synthesized within the cells. Glutamine 
ingestion studies have definitely demonstrated that both leukocytes and platelets 
can concentrate glutamine from plasma. The glutamine levels in these formed elements 
of the blood were observed to increase when the plasma level increased and to fall 
when the plasma level returned to the control level (see part VI). 
The present findings are to be contrasted with some of the reports in the litera- 
ture! 16, 20, 22. Tn our opinion the highly variable findings reported by other in- 
vestigators are related to the variations encountered in leukemia and in the small 
number of samples examined by these investigators. Previous studies (other than 
amino nitrogen determinations) have been carried out on single samples from each 
patient and variability cannot be determined in this way. The practice of grouping 
treated and untreated patients in the same category for determination of free amino 
acid levels is quite unjustified, and evidence of marked changes as a result of drug 
therapy are presented in parts IV and V. 
The information obtained in our investigations of chronic granulocytic leukemia 
and polycythemia do not appear to lend support to the concept advanced by 
CHRISTENSEN AND HENDERSON?$ and subsequently made into a general theory of 
cancer by WISEMAN AND GHADIALLY”’. Their thesis is that the selective advantage 
of tumor cells that allows them to grow and reproduce in the host without the control 
normally exerted by the host is an increased ability to capture free amino acids. 
Although it is true that the leukocytes, platelets, and to a lesser extent erythrocytes 
may have increased free amino acid pools in some cases of leukemia, this appears to 
be associated with similar changes in the plasma levels and the findings are variable. 
The simplest interpretation of the present findings is that the uptake of free amino 
acids by leukemic leukocytes is not particularly different from the uptake by normal 
cells, at least where morphologically similar cells from normal individuals and 
patients with leukemia can be compared. It is true that the myelocytes do contain 
larger concentrations of free amino acids than the neutrophilic polymorphonuclear 
leukocytes of either normal humans or patients with leukemia. The significance of 
this cannot be judged as morphologically similar cells of normal individuals are 
not available for study. The fact that myeloblasts contain very large amounts of 
taurine, glutamic acid, and ethanolamine phosphate, but smaller amounts of some 
of the other free amino acids demonstrates that the large free amino acid pool of 
myelocytes is not a characteristic of all immature cells. All of these findings indicate 
that the free amino acid pools as.studied in the present investigations are not directly 
related to the basic underlying cause of the disease. The free amino acid pools are 
related to leukocyte metabolism, permeability, and concentrative ability that differ 
depending upon the type of cell. 
References p. 447/448 
