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Purine and Pyrimidine Ribonucleoside Monophosphate Patterns of Peripheral Blood and Bone Marrow Cells in Human Acute Leukemias

Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, Case 906, 13288 Marseille Cedex 9 [J. S., H. L. C.], and Institut J. Paoli I. Calmettes, 232, bd de Sainte-Marguerite, BP 156, 13273 Marseille Cedex 9 [D. M., J-A. G., Y. C.], France

Purine and pyrimidine ribonucleoside monophosphate (NMP) levels were measured in blood and/or bone marrow cells of groups of patients with acute leukemia including: (a) acute lymphoblastic leukemia (ALL); and (b) acute nonlymphoblastic leukemia (ANLL) (acute myeloblastic, promyelocytic, myelomonocytic, and monoblastic leukemia). Patients were either untreated or in remission (17 with ANLL and six with ALL); three relapsed patients with ALL were also studied. Phytohemagglutinin-stimulated tonsil lymphocytes and bone marrow cells both from normal subjects were used as controls. Moreover, observations in acute leukemias were compared with those in chronic leukemias.

The cytidine, adenosine, guanosine, and uridine 2'-, 3'-, and 5'-monophosphate contents were measured by high-performance liquid chromatography. Using this technique, relatively difficult separations (e.g., adenosine of 2'-, 3'- and 5'-monophosphates) were achieved fairly rapidly by isocratic elution. 2'- and 3'-NMP concentrations were 2.5 times higher (0.69 to 1.38 x 10^-9 mol/10⁶ cells in the peripheral blood and 2.42 to 5.87 x 10^-9 mol/10⁶ cells in the bone marrow) in ALL and were 5.5 times higher (1.66 to 3.82 x 10^-9 cells in the peripheral blood and 4.30 to 9.27 x 10^-9 mol/10⁶ cells in the bone marrow) in ANLL leukemic cells than in chronic leukemic blood cells or control bone marrow cells (0.34 to 0.75 and 0.93 to 1.63 x 10^-9 mol/10⁶ cells, respectively). 2'- NMPs were found only in leukemic blast cells and accounted for about 30% of 2'- and 3'-NMP mixtures. Levels of 2'- and 3'-NMP were around 2- and 4-fold higher in bone marrow than in peripheral blood cells of patients. The high level of 2'- and 3'-NMP found in bone marrow and blood cells of untreated ALL patients decreased during remission without reverting to normal; however, in relapse, it was 5 to 10 times higher than in the case of untreated patients.

The 5'-NMP concentrations were always lower than those of 2'- and 3'-NMP (e.g., cytidine 5'-monophosphate = 0.29 x 10^-9 mol/10⁶ cells and cytidine 2'- and 3'-monophosphates = 6.40 x 10^-9 mol/10⁶ cells in bone marrow of untreated patients with ANLL) and were the same in acute leukemias and control (including chronic leukemias). Furthermore, 5'-NMP levels remained constant during the course of the disease. 2'- and 3'-NMP levels appear therefore to be useful markers of leukemic blasts and may facilitate both the diagnostic of acute leukemia and the monitoring of chemotherapy.

¹ To whom requests for reprints should be addressed.

Received 4/ 8/81. Accepted 12/ 9/81.