We have investigated human
lactate dehydrogenase (LDH)
isoenzymes and human
nuclear matrix protein 41/7 (NMP 41/7) as potential serologic markers to monitor the course of human
leukemia in severe combined immunodeficient (SCID) mice. Following the
transplantation of 10(6) human
acute lymphoblastic leukemia (ALL) Nalm-6 cells, human specific LDH
isoenzymes were measurable in the serum of SCID mice as early as 7 days after
transplantation, although serum total LDH increased in some animals as early as 5 days after
transplantation. Human NMP 41/7 was measurable in all animals at day 15 after
leukemia cell injection. Serum levels of total LDH, human specific LDH and NMP 41/7 increased progressively over time, reaching total LDH levels as high as 50,000 U/L at day 25 after
transplantation. To determine whether the levels of LDH and NMP 41/7 in serum were a reflection of human
tumor burden, we studied these serologic markers in SCID mice bearing measurable subcutaneous human
neuroblastoma tumors, or compared the serum levels of these markers with the number of human
leukemia CD10+ cells in the bone marrow of the SCID mice. The serum levels of total LDH, human specific LDH
isoenzymes, and NMP 41/7 correlated well with
tumor burden, and they drastically decreased or disappeared from serum after the human
leukemia or
neuroblastoma cells were selectively killed with a single intravenous (IV) injection of 1 to 3 micrograms
diphtheria toxin (DT) (the cellular receptor for DT is present on human cells, but not on mouse cells). Paraplegic mice with central nervous system
leukemia completely recovered after DT treatment. We conclude that measurements of serum levels of total LDH, human LDH
isoenzymes, and NMP 41/7 are sensitive, quantitative, rapid, and easy to perform serologic methods useful to monitor the engraftment, progression, and treatment response of human
leukemia in SCID mice.