HDAC inhibitors induce apoptosis in glucocorticoid-resistant acute lymphatic leukemia cells despite a switch from the extrinsic to the intrinsic death pathway

Tsapis, Michael; Lieb, Michèle; Manzo, Fabio; Shankaranarayanan, Pattabhiraman; Herbrecht, Raoul; Lutz, Patrick; Gronemeyer, Hinrich

doi:10.1016/j.biocel.2007.03.009

Cited by 46 publications

(38 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results validated earlier reports on cancer cells, 35 leukemia cells 18 and fresh CLL B cells. [20][21][22] Interestingly, we also observe that VPA induces apoptosis in cells from patients with unfavorable cytogenetic abnormalities such as 6q deletion, 17p deletion or showing a complex karyotype (Supplementary data 6).…”

Section: Discussionsupporting

confidence: 90%

Antileukemic activity of valproic acid in chronic lymphocytic leukemia B cells defined by microarray analysis

et al. 2009

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 90%

Antileukemic activity of valproic acid in chronic lymphocytic leukemia B cells defined by microarray analysis

et al. 2009

View full text Add to dashboard Cite

“…Acetylation/deacetylation balance has been recently suggested to have a role in the development and progression of T-cell acute lymphoblastic leukemia (T-ALL), a very aggressive disease, which accounts for 10-15% of pediatric and 25% of adult ALL cases. Indeed, HDAC inhibitors (HDACi) have been recently shown to display anti-tumor activity upon glucocorticoid resistant T-ALL cell lines and patientderived blasts, confirming therapeutic efficacy observed in other tumors (for example, B-cell acute lymphoblastic leukemia, chronic myeloid leukemia and a number of solid tumors) (Tsapis et al, 2007;Zhang et al, 2010).…”

Section: Introductionmentioning

confidence: 81%

Acetylation controls Notch3 stability and function in T-cell leukemia

Palermo

Checquolo²,

Giovenco

et al. 2011

Oncogene

View full text Add to dashboard Cite

“…Valproic acid (VPA) significantly increased TRAIL-sensitivity of patient-derived primary chronic lymphocytic leukemia (CLL) cells by downregulating c-FLIP [17] and in an established chronic myeloid leukemia (CML) cell line by increasing expression of DR4 and DR5 [18]. Suberoylanilide hydroxamic acid (SAHA) also augmented TRAIL-mediated cytotoxicity in various established acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and chronic myeloid leukemia (CML) cells by amplifying the extrinsic and intrinsic pathways [19][20][21]. HDACIs combined with agonistic mAbs specific to DR4 or DR5 have also shown synergistic apoptosis-inducing activity in various solid tumors [22] and in primary CLL cells [23,24].…”

Section: Introductionmentioning

confidence: 99%

Histone deacetylase inhibitors synergistically potentiate death receptor 4-mediated apoptotic cell death of human T-cell acute lymphoblastic leukemia cells

et al. 2010

View full text Add to dashboard Cite

Cell-death signaling through the pro-apoptotic tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptors, death receptor 4 (DR4) and DR5, has shown tumor-selective apoptotic activity. Here, we examine susceptibility of various leukemia cell lines (HL-60, U937, K562, CCRF-CEM, CEM-CM3, and THP-1) to an anti-DR4 agonistic monoclonal antibody (mAb), AY4, in comparison with TRAIL. While most of the leukemia cell lines were intrinsically resistant to AY4 or TRAIL alone, the two T-cell acute lymphoblastic leukemia (T-ALL) lines, CEM-CM3 and CCRF-CEM cells, underwent synergistic caspase-dependent apoptotic cell death by combination of AY4 or TRAIL with a histone deacetylase inhibitor (HDACI), either suberoylanilide hydroxamic acid (SAHA) or valproic acid (VPA). All of the combined treatments synergistically downregulated several antiapoptotic proteins (c-FLIP, Bcl-2, Bcl-X L , XIAP, and survivin) without significant changing the expression levels of pro-apoptotic proteins (Bax and Bak) or the receptors (DR4 and DR5). Downregulation of c-FLIP to activate caspase-8 was a critical step for the synergistic apoptosis through both extrinsic and intrinsic apoptotic pathways. Our results demonstrate that the HDACIs have synergistic effects on DR4-specific mAb AY4-mediated cell death in the T-ALL cells with comparable competence to those exerted by TRAIL, providing a new strategy for the targeted treatment of human T-ALL cells.

show abstract

HDAC inhibitors induce apoptosis in glucocorticoid-resistant acute lymphatic leukemia cells despite a switch from the extrinsic to the intrinsic death pathway

Cited by 46 publications

References 13 publications

Antileukemic activity of valproic acid in chronic lymphocytic leukemia B cells defined by microarray analysis

Antileukemic activity of valproic acid in chronic lymphocytic leukemia B cells defined by microarray analysis

Acetylation controls Notch3 stability and function in T-cell leukemia

Histone deacetylase inhibitors synergistically potentiate death receptor 4-mediated apoptotic cell death of human T-cell acute lymphoblastic leukemia cells

Contact Info

Product

Resources

About