Expression Pattern of Mitochondrial ND2 Gene in Human Leukemia and in HL60 Cells During Growth and Differentiation.

Abstract

We differentially screened 5,000 clones from a cDNA library of acute myelogenous leukemia (AML) cell line HL60 using cDNA probes derived from normal granulocytes or from acute myelomonocytic leukemia cells, the objective being to identify genes preferentially expressed in myeloid lineage leukemic cells. One clone, corresponding to a mitochondrial DNA fragment, including NADH dehydrogenase subunit 2 (ND2) gene, was selected for use as a probe. We examined expression of the ND2 gene in various leukemic cell populations and in normal peripheral blood cells. DNA-RNA hybridization studies revealed that ND2 messenger RNA (mRNA) was more markedly expressed in AML cells than in other leukemic cells and normal peripheral blood granulocytes. The expression of ND2 mRNA decreased in HL60 cells several hours after treatment with phorbol myristate acetate (PMA), or dimethyl sulfoxide (DMSO). However, the ND2 gene expression did not depend on the growth-state of HL60 cells because the steady-state level of its expression was observed during transitions of growth. These results suggest that ND2 mRNA is involved in the maturation of myeloid cells and in cellular differentiation, in a lineage-preferential manner. A comparison of the nucleotide sequence of this clone with the documented human mitochondrial DNA sequence revealed several single-base substitutions, insertions and a 39-bases insertion.