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MN1 is indispensable for MLL-rearranged acute myeloid leukemia.
Abstract Mixed lineage leukemia (MLL/KMT2A) rearrangements (MLL-r) are one of the most frequent chromosomal aberrations in acute myeloid leukemia. We evaluated the function of Meningioma 1 (MN1), a cofactor of HOXA9 and MEIS1, in human and murine MLL-rearranged leukemia by CRISPR-Cas9 mediated deletion of MN1. MN1 was required for in vivo leukemogenicity of MLL positive murine and human leukemia cells. Loss of MN1 inhibited cell cycle and proliferation, promoted apoptosis and induced differentiation of MLL-rearranged cells. Expression analysis and chromatin immunoprecipitation with sequencing from previously repor...
Source: Haematologica - August 13, 2019 Category: Hematology Authors: Sharma A, Jyotsana N, Gabdoulline R, Heckl D, Kuchenbauer F, Slany RK, Ganser A, Heuser M Tags: Haematologica Source Type: research

The microenvironmental stromal cells abrogate NF- κB inhibitor induced apoptosis in chronic lymphocytic leukemia.
The microenvironmental stromal cells abrogate NF-κB inhibitor induced apoptosis in chronic lymphocytic leukemia. Haematologica. 2017 Nov 09;: Authors: Simon-Gabriel CP, Foerster K, Saleem S, Bleckmann D, Benkisser-Petersen M, Thornton N, Umezawa K, Decker S, Burger M, Veelken H, Claus R, Dierks C, Duyster J, Zirlik K Abstract NF-κB is known to play an important role in the pathogenesis of chronic lymphocytic leukemia. Several NF-κB inhibitors have been shown to successfully induce apoptosis of chronic lymphocytic leukemia cells in vitro. Since the microenvironment is known to be crucial for the sur...
Source: Haematologica - November 9, 2017 Category: Hematology Authors: Simon-Gabriel CP, Foerster K, Saleem S, Bleckmann D, Benkisser-Petersen M, Thornton N, Umezawa K, Decker S, Burger M, Veelken H, Claus R, Dierks C, Duyster J, Zirlik K Tags: Haematologica Source Type: research

The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma.
Ocio EM Abstract Kinesin spindle protein inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (ARRY-520), an inhibitor if this proteins, has demonstrated activity in heavily pretreated multiple myeloma patients. The aim of this work was to investigate the activity of filanesib in combination with pomalidomide plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect.The ability of filanesib to enhance the activity of pomalidomide plus dexamethasone was studied in several in vitro and in vivo models. Mechanisms of this synergistic combinati...
Source: Haematologica - August 31, 2017 Category: Hematology Authors: Hernández-García S, San-Segundo L, González-Méndez L, Corchete LA, Misiewicz-Krzeminska I, Martín-Sánchez M, López-Iglesias AA, Algarín EM, Mogollón P, Díaz-Tejedor A, Paíno T, Tunquist B, Mateos MV, Gutiérrez NC, Díaz-Rodriguez E, Garayoa M, Tags: Haematologica Source Type: research

The transcription factor GATA1 regulates NBEAL2 expression through a long-distance enhancer.
In conclusion, we here show a long-distance regulatory region with GATA1 binding sites as strong enhancer for NBEAL2 expression. PMID: 28082341 [PubMed - as supplied by publisher]
Source: Haematologica - January 11, 2017 Category: Hematology Authors: Wijgaerts A, Wittevrongel C, Thys C, Devos T, Peerlinck K, Tijssen MR, Van Geet C, Freson K Tags: Haematologica Source Type: research

The small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma and full length FOXP1 exert similar oncogenic and transcriptional activity in human B cells.
Abstract The forkhead transcription factor FOXP1 is generally regarded as an oncogene in activated B cell-like diffuse large B-cell lymphoma. Previous studies have suggested that a small isoform of FOXP1 (FOXP1-iso), rather than full-length FOXP1 (FOXP1-FL), may possess this oncogenic activity. Corroborating those studies, we here show that activated B cell-like diffuse large B-cell lymphoma cell-lines and primary activated B cell-like diffuse large B-cell lymphoma cells predominantly express FOXP1-iso and that the 5-end of the Foxp1 gene is a common insertion site in murine lymphomas in leukaemia virus- and trans...
Source: Haematologica - November 30, 2016 Category: Hematology Authors: van Keimpema M, Grüneberg LJ, Schilder-Tol EJ, Oud ME, Beuling E, Hensbergen PJ, de Jong J, Pals ST, Spaargaren M Tags: Haematologica Source Type: research

Antineoplastic effects of liposomal siRNA treatment targeting BLIMP1/PRDM1 in primary effusion lymphoma.
PMID: 26206802 [PubMed - as supplied by publisher]
Source: Haematologica - July 23, 2015 Category: Hematology Authors: Riva G, Lagreca I, Mattiolo A, Belletti D, Lignitto L, Barozzi P, Ruozi B, Vallerini D, Quadrelli C, Corradini G, Forghieri F, Marasca R, Narni F, Tosi G, Forni F, Vandelli MA, Amadori A, Chieco-Bianchi L, Potenza L, Calabro' ML, Luppi M Tags: Haematologica Source Type: research

Synergistic growth-inhibitory effects of ponatinib and midostaurin (PKC412) on neoplastic mast cells carrying KIT D816V.
We examined the effects of the multi-kinase blocker ponatinib on neoplastic mast cells and asked whether ponatinib would synergize with other antineoplastic drugs. Ponatinib was found to inhibit the kinase activity of KIT G560V and KIT D816V in the human mast cell leukemia cell line HMC-1. In addition, ponatinib was found to block Lyn- and STAT5 activity in neoplastic mast cells. Ponatinib induced growth inhibition and apoptosis in HMC-1.1 cells (KIT G560V+) and HMC-1.2 cells (KIT G560V+/KIT D816V+) as well as in primary neoplastic mast cells. The effects of ponatinib were dose-dependent, but higher IC50-values were obtain...
Source: Haematologica - March 28, 2013 Category: Hematology Authors: Gleixner KV, Peter B, Blatt K, Suppan V, Reiter A, Radia D, Hadzijusufovic E, Valent P Tags: Haematologica Source Type: research