"In vitro citlivost a rezistence Bcr/Abl leukemick\u00FDch bun\u011Bk k STI571" . "0"^^ . . "STI571 inhibits the Bcr/Abl tyrosine kinase, and is therefore the treatment choice of Ph positive malignancies. Because of the emerging problem of resistance, a definition of cellular and molecular factors affecting sensitivity and resistance of Bcr/Abl cells to STI571 is urgently needed. We propose: A. to test residual, in vitro-STI571-resistant subclones derived from patients, for qualitative (using sequencing of BCR/ABL ATP-binding pocket) and also possible quantitative gene changes using DNA array technology. We hypothesize that pre-existing genomic alterations in a subsest of BCR/ABL positive cells obtained from heavily-pretreated patients may lead to resistant phenotype later in the therapy.B. Recently, we participated on analysis of a unique cellular model of STI571-resistance, KBM5-STI5871-R cell line. The KBM5 cells display defect in induction of apoptosis, while activating block of cell cycle checkpoint when treated with STI571. In our earlier study, we have shown that N6-substituted"@en . . . "Neuvedeno."@en . "1"^^ . . . . . . "7"^^ . "Sensitivity and resistance of Bcr/Abl leukemia cells to STI571 in vitro"@en . "7"^^ . "STI571 (imatinib mesylate, IM), specifick\u00FD inhibitor Bcr/Abl tyrozinov\u00E9 kin\u00E1zy, se stal z\u00E1kladn\u00ED terapeutickou modalitou Ph pozitivn\u00EDch leukemi\u00ED. Vzhledem k nar\u016Fstaj\u00EDc\u00ED rezistenci na tento l\u00E9k je nutn\u00E9 definovat molekul\u00E1rn\u00ED mechanizmy, ovliv\u0148uj\u00EDc\u00ED jak citlivost, tak rezistenci BCR/ABL bun\u011Bk k IM.Navrhujeme: A. Testovat IM-rezistentn\u00ED subklony, z\u00EDskan\u00E9 in vitro kultivac\u00ED BCR/ABL progenitor\u016F, pro kvalitativn\u00ED a kvantitativn\u00ED genov\u00E9 zm\u011Bny sekvenov\u00E1n\u00EDm ABL-kin\u00E1zov\u00E9 dom\u00E9ny a technologi\u00ED DNA-array. P\u0159edpokl\u00E1d\u00E1me, \u017Ee se u siln\u011B p\u0159edl\u00E9\u010Den\u00FDch nemocn\u00FDch vyskytuj\u00ED v \u010D\u00E1sti BCR/ABL-pozitivn\u00EDch bun\u011Bk preexistuj\u00EDc\u00ED genomick\u00E9 zm\u011Bny, kter\u00E9 mohou vy\u00FAstit v pozd\u011Bj\u0161\u00ED rezistenci na IM.B. Ve spolupr\u00E1ci s M.D.Anderson Cancer Center v Houstonu jsme na molekul\u00E1rn\u00ED \u00FArovni analyzovali unik\u00E1tn\u00ED BCR/ABL bun\u011B\u010Dn\u00FD model, bun\u011B\u010Dnou linii KBM5-STI571-R. im u KBM5 linie nespou\u0161t\u00ED programovanou bun\u011B\u010Dnou smrt (apopt\u00F3zu), ale indukuje zastaven\u00ED bun\u011B\u010Dn\u00E9ho cyklu. Na z\u00E1klad\u011B p\u0159edchoz\u00EDch experiment\u016F p\u0159edpokl\u00E1d\u00E1me, \u017Ee" . . "GA301/04/1239" . . . . "2007-10-16+02:00"^^ . . . . "http://www.isvav.cz/projectDetail.do?rowId=GA301/04/1239"^^ . . "STI571 (imatinib mesylate) inhibits the Bcr/Abl tyrosine kinase, and is therefore the treatment choice of Ph positive malignancies. We characterized on cytogenetic and/or molecular levels mechanisms of sensitivity or resistance to imatinib in about 100 o"@en . "STI571 (imatinib mesylate), specifick\u00FD inhibitor Bcr/Abl tyrozinov\u00E9 kin\u00E1zy, se stal z\u00E1kladn\u00ED terapeutickou modalitou Bcr/Abl pozitivn\u00EDch leukemi\u00ED. Odhalili jsme cytogenetickou a/nebo molekul\u00E1rn\u00ED podstatu citlivosti nebo rezistence na tento l\u00E9k na z\u00E1klad\u011B"@cs . . . . "0"^^ . .