NDRG1/2 expression is inhibited in primary acute myeloid leukemia

• Published in: Leukemia research 2010-03, Vol.34 (3), p.393-398
• Main Authors: Tschan, Mario P, Shan, Deborah, Laedrach, Judith, Eyholzer, Marianne, Leibundgut, Elisabeth Oppliger, Baerlocher, Gabriela M, Tobler, Andreas, Stroka, Deborah, Fey, Martin F
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia (AML); Acute promyelocytic leukemia (APL); Antineoplastic Agents - pharmacology; Blotting, Western; c-Myc; Cell Cycle Proteins - biosynthesis; Cell Cycle Proteins - drug effects; Cell Cycle Proteins - genetics; Cell Differentiation - physiology; Gene Expression; Granulocytic differentiation; Hematology, Oncology and Palliative Medicine; Humans; Intracellular Signaling Peptides and Proteins - drug effects; Intracellular Signaling Peptides and Proteins - genetics; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Macrophages - cytology; Macrophages - metabolism; N-myc downstream regulated gene 1 (NDRG1); NDRG2; Neutrophils - cytology; Neutrophils - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Tretinoin - pharmacology; Tumor Suppressor Proteins - biosynthesis; Tumor Suppressor Proteins - genetics
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2009.08.037

Abstract Expression of N-myc downregulated gene 1 (NDRG1) is associated with growth arrest and differentiation of tumor cells. In hematopoietic cells, NDRG1 was identified in a screen for differentiation-related genes in human myelomonocytic leukemic U937 cells. In the present study, we found significantly higher NDRG1 mRNA levels in granulocytes of healthy donors than in primary acute myeloid leukemia (AML) cells. Another NDRG family member, NDRG2, was significantly higher expressed in normal macrophages compared to primary AML cells. Moreover, NDRG1 mRNA levels increased in two acute promyelocytic leukemia (APL) patients as well as in NB4 and HT93 APL cells upon all- trans retinoic acid (ATRA) therapy. In line with these observations, silencing of NDRG1 diminished neutrophil differentiation of leukemic cell lines. In conclusion, we found an association of low NDRG1 levels with an immature cell phenotype and provide evidence that NDRG1 is functionally involved in neutrophil maturation.