Identity of differentiation inhibiting factor for mouse myeloid leukemia cells with Nm23/nucleoside diphosphate kinase

Abstract

Mouse myeloid leukemic M1 cell lines can be induced to differentiate into monocyte/macrophage pathways by various inducers. We have isolated resistant M1 cells that cannot be induced to differentiate into mature cells from the parent M1 cells. The induction of differentiation of M1 cells can be inhibited by protein inhibitors termed differentiation-inhibiting factors (I-factors) in a cell lysate and conditioned medium of the differentiation resistant M1 cells. Production of the I-factor activity in resistant M1 cells is well associated with development of resistance of M1 cells to differentiation inducers. We have purified one of the I-factors from conditioned medium of differentiation-resistant M1 cells. The purified I-factor has a relative molecular mass of approximately 16 000–17 000 Da (16K I-factor) and the amino acid sequences of all fragments of the 16K I-factor are identical with Nm23/nucleoside diphosphate kinase (EC2.7.4.6) protein involved in tumor metastasis. The findings indicate that the I-factor is Nm23/nucleoside diphosphate kinase protein.