Induction of differentiation in human myeloid leukemia cells with cytosine arabinoside

Normalization of granulocyte counts was obtained with low-dose cytosine arabinoside (Ara-C) in a patient with acute myelogenous leukemia (AML, FAB-M2) who had relapsed on maintenance therapy containing conventional doses of Ara-C and was clinically resistant to high-dose Ara-C treatment. The patient's leukemic cells exhibited an abnormal karyotype (45, X-Y, t[8q; 21q]). To determine whether the response to low-dose Ara-C was a result of induced leukemic cell differentiation, the mature peripheral blood granulocytes were isolated and fused with mitotic chinese hamster ovary (CHO) cells to induce premature chromosome condensation. Karyotypic evaluation of the granulocyte prematurely condensed chromosomes (PCC) during response to low-dose Ara-C demonstrated the presence of cells with 45 chromosomes. This result strongly suggests that part of this patient's response to low-dose Ara-C was a result of induced maturation of the leukemic clone.