Relationship of Queuine-lacking Transfer RNAs to the Grade of Malignancy in Human Leukemias and Lymphomas1

To elucidate the significance of tRNA modification for human lymphoid maturation and malignant transformation, the amount of tRNAs having guanosine in place of queuosine, i.e., (Q-)tRNA, was determined in several human lymphomas and leukemias by exchanging the respective unmodified guanosine residue for [3H]guanine, a reaction catalyzed by a specific tRNA transglycosylase from Escherichia coli. The amount of (Q-)tRNA in highgrade lymphomas (mean ±SD, 38.64 ±22.81) is substantially greater than that observed in germinal center cell lymphomas (7.15 ±4.0) and chronic lymphocytic leukemia at a favorable prognostic stage (4.63 ±1.84) and in non-neoplastic lymphoid tissues (4.52 ±3.17). In chronic lymphocytic leukemia lympho cytes it increases from stage A to C of the Binet classification: 4.63 ±1.84 (A); 9.25 ±1.45 (B); and 25.87 ±8.9 (C). Increasing values were also observed in representatives of late B-cell dif ferentiation (hairy cell leukemia, 14.8 ±0.4; immunocytoma and plasmacytoma, 21.58 ±4.62). On electrophoresis, a characteristic pattern of undermodified tRNA species was found in some neoplastic cells. Determination of free queuine in neoplastic and non-neoplastic human lymphatic specimens suggests that undermodification of tRNA does not arise from substrate limitation. The results indicate that a de creased queuosine content of tRNA is not a general feature of neoplasms, but it may be important for disease activity and perhaps also for the state of maturation in human lymphomas and leukemias.