Epigenetic modulation of gene expression of human leukemia cell lines - induction of cell death and senescence.

Histone deacetylase inhibitors (HDACi) are emerging new class of anticancer agents that act by inhibiting cell growth, inducing cell cycle arrest and apoptosis of various cancer cells. However, in some conditions, apoptosis can be blocked and non apoptotic cell death and irreversible growth arrest, namely senescence, can be activated as potential tumor-suppressor mechanism. Here we evaluated the dosage effects of HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA) in a series of human leukaemia cell lines.

Suberoylanilide hydroxamic acid (SAHA) at subtoxic concentrations increases the adhesivity of human leukemic cells to fibronectin.

Suberoylanilide hydroxamic acid (SAHA) is an inhibitor of histone deacetylases (HDACs) which is being introduced into clinic for the treatment of hematological diseases. We studied the effect of this compound on six human hematopoietic cell lines (JURL-MK1, K562, CML-T1, Karpas-299, HL-60, and ML-2) as well as on normal human lymphocytes and on leukemic primary cells. SAHA induced dose-dependent and cell type-dependent cell death which displayed apoptotic features (caspase-3 activation and apoptotic DNA fragmentation) in most cell types including the normal lymphocytes.

Growth inhibitory effect of the antibody to hematopoietic stem cell antigen CD34 in leukemic cell lines.

Growth-inhibitory and proapoptotic effects of the monoclonal antibody to CD34 molecule, clone 4H11, were tested in CD34+ leukemic cell lines (MOLM-9, JURL-MK1, HEL) and CD34- cell lines (PS-1, ML-2 and CTV-1). We have found that the monoclonal antibody to CD34 inhibited the proliferation and induced apoptosis of all CD34+ cell lines. We did not observe induction of differentiation by anti-CD34 antibody, but a growth arrest of cells in the G0/G1 phase of the cell cycle was detected in all the cell lines studied.