cyclin-d1 and Blast-Crisis

cyclin-d1 has been researched along with Blast-Crisis* in 2 studies

Other Studies

2 other study(ies) available for cyclin-d1 and Blast-Crisis

Article	Year
Cyclin D1-negative blastoid mantle cell lymphoma exhibiting cleaved to bilobated cytomorphology. Blood, 2017, 05-11, Volume: 129, Issue:19 Topics: Aged; Blast Crisis; Cyclin D1; Humans; Lymphoma, Mantle-Cell; Male	2017
Pharmacologic co-inhibition of Mnks and mTORC1 synergistically suppresses proliferation and perturbs cell cycle progression in blast crisis-chronic myeloid leukemia cells. Cancer letters, 2015, Feb-28, Volume: 357, Issue:2 The Ras/Raf/MAPK and PI3K/Akt/mTORC1 cascades are two most aberrantly regulated pathways in cancers. As MAPK-interacting kinases (Mnks) are part of the convergent node of these two pathways, and play a pivotal role in cellular transformation, targeting Mnks has emerged as a potential therapeutic strategy. Herein, a dual-specific Mnk1/2 inhibitor MNKI-57 and a potent Mnk2-specific inhibitor MNKI-4 were selected for a panel screen against 28 human cancer cell lines. The study reveals that MNKI-57 and MNKI-4 are most potent against leukemia cells KYO-1 (i.e. BC-CML) and KG-1 (i.e. AML). Interestingly, we found that sensitivity of selected leukemia cells to Mnk inhibitors is correlated with the level of phosphorylated 4E-BP1 at Thr70. The anti-proliferative effects of Mnk inhibitors are cytostatic in the sensitive KYO-1 cells, inducing significant G1 arrest via down-regulation of cyclin D1 expression. In KYO-1 cells where Akt is not constitutively active, Mnk inhibitors increase the sensitivity of cells to rapamycin, resulting in a more pronounced anti-proliferative activity. Remarkably, the synergistic anti-proliferative effects are associated with a marked de-phosphorylation of 4E-BP1 at Thr70. Collectively, these data highlight the importance of 4E-BP1 as a key integrator in the MAPK and mTORC1 cascades, and suggest that a combined pharmacologic inhibition of mTORC1 and Mnk kinases offers an innovative therapeutic opportunity in BC-CML. Topics: Adaptor Proteins, Signal Transducing; Apoptosis; Blast Crisis; Blotting, Western; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cyclin D1; Drug Synergism; Enzyme Inhibitors; Flow Cytometry; G1 Phase Cell Cycle Checkpoints; HCT116 Cells; HT29 Cells; Humans; Intracellular Signaling Peptides and Proteins; K562 Cells; MCF-7 Cells; Mechanistic Target of Rapamycin Complex 1; Molecular Structure; Multiprotein Complexes; Phosphoproteins; Phosphorylation; Protein Serine-Threonine Kinases; Reverse Transcriptase Polymerase Chain Reaction; Threonine; TOR Serine-Threonine Kinases; U937 Cells	2015

Article

Year

Cyclin D1-negative blastoid mantle cell lymphoma exhibiting cleaved to bilobated cytomorphology.

Blood, 2017, 05-11, Volume: 129, Issue:19

Topics: Aged; Blast Crisis; Cyclin D1; Humans; Lymphoma, Mantle-Cell; Male

2017

Pharmacologic co-inhibition of Mnks and mTORC1 synergistically suppresses proliferation and perturbs cell cycle progression in blast crisis-chronic myeloid leukemia cells.

Cancer letters, 2015, Feb-28, Volume: 357, Issue:2

The Ras/Raf/MAPK and PI3K/Akt/mTORC1 cascades are two most aberrantly regulated pathways in cancers. As MAPK-interacting kinases (Mnks) are part of the convergent node of these two pathways, and play a pivotal role in cellular transformation, targeting Mnks has emerged as a potential therapeutic strategy. Herein, a dual-specific Mnk1/2 inhibitor MNKI-57 and a potent Mnk2-specific inhibitor MNKI-4 were selected for a panel screen against 28 human cancer cell lines. The study reveals that MNKI-57 and MNKI-4 are most potent against leukemia cells KYO-1 (i.e. BC-CML) and KG-1 (i.e. AML). Interestingly, we found that sensitivity of selected leukemia cells to Mnk inhibitors is correlated with the level of phosphorylated 4E-BP1 at Thr70. The anti-proliferative effects of Mnk inhibitors are cytostatic in the sensitive KYO-1 cells, inducing significant G1 arrest via down-regulation of cyclin D1 expression. In KYO-1 cells where Akt is not constitutively active, Mnk inhibitors increase the sensitivity of cells to rapamycin, resulting in a more pronounced anti-proliferative activity. Remarkably, the synergistic anti-proliferative effects are associated with a marked de-phosphorylation of 4E-BP1 at Thr70. Collectively, these data highlight the importance of 4E-BP1 as a key integrator in the MAPK and mTORC1 cascades, and suggest that a combined pharmacologic inhibition of mTORC1 and Mnk kinases offers an innovative therapeutic opportunity in BC-CML.

Topics: Adaptor Proteins, Signal Transducing; Apoptosis; Blast Crisis; Blotting, Western; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cyclin D1; Drug Synergism; Enzyme Inhibitors; Flow Cytometry; G1 Phase Cell Cycle Checkpoints; HCT116 Cells; HT29 Cells; Humans; Intracellular Signaling Peptides and Proteins; K562 Cells; MCF-7 Cells; Mechanistic Target of Rapamycin Complex 1; Molecular Structure; Multiprotein Complexes; Phosphoproteins; Phosphorylation; Protein Serine-Threonine Kinases; Reverse Transcriptase Polymerase Chain Reaction; Threonine; TOR Serine-Threonine Kinases; U937 Cells

2015