We have found that the L-system of amino acid transport is nearly absent in chronic lymphocytic leukemia (CLL) lymphocytes when compared to blood lymphocytes (T-enriched) or tonsillar lymphocytes (B-enriched). We have further established that the L-system of transport is also markedly diminished when CLL cells are compared to normal human blood B-lymphocytes. We plan to examine the effect of stimulation with B-cell mitogens on the kinetic parameters of L-system uptake. In particular, we will determine if a rudimentary L-system of amino acid transport can be activated in CLL cells by new RNA and protein synthesis under conditions leading to mitogenesis. Our preliminary data indicate that the L-system in CLL cells has a profoundly decreased maximal velocity of transport (one-tenth that of the other lymphocyte types) for the L-system of amino acid transport. We intend to characterize the membrane proteins associated with the L-system in normal B-lymphocytes using photoreactive, radiolabeled amino acids and other photoreactive probes in conjunction with protein separation techniques. We then will determine if these proteins are reduced or absent in the membranes of CLL lymphocytes. These studies will compare the amino acid transport systems, both physiologically and biochemically, in CLL and normal B-lymphocytes to define the specific abnormality in L-system transport that we have discovered in leukemic lymphocytes. (A)
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