000164356 001__ 164356
000164356 005__ 20181203022328.0
000164356 0247_ $$2doi$$a10.1038/leu.2008.65
000164356 022__ $$a0887-6924
000164356 037__ $$aARTICLE
000164356 245__ $$aCharacterization of BCR-ABL deletion mutants from patients with chronic myeloid leukemia
000164356 269__ $$a2008
000164356 260__ $$bNature Publishing Group$$c2008
000164356 336__ $$aJournal Articles
000164356 520__ $$aThe BCR-ABL oncogenic tyrosine kinase causes chronic myeloid leukemia and is the target for imatinib therapy. During imatinib treatment, cells are selected in some patients with BCR-ABL kinase domain mutations that render decreased drug sensitivity. In addition, some patients express deletion mutants of BCR-ABL, apparently due to missplicing. Most commonly these deletion mutants lack a significant portion of the kinase domain that includes the P-loop. We describe a screen for such mutations in patients with CML and demonstrate that they are not oncogenic and are catalytically inactive. We hypothesized that coexpressing BCR-ABL deletion mutants has a dominant-negative effect on the native form through heterocomplex formation. However, upon coexpression of native and deletion mutant BCR-ABL in Ba/F3 cells, growth factor independence is maintained and signaling is activated normally. Despite this, these cells have increased imatinib sensitivity compared to cells expressing only native BCR-ABL. Thus, it will be important to investigate the prognostic impact of coexpression of deletion mutants in CML patients during imatinib treatment.
000164356 6531_ $$aSequence Deletion
000164356 700__ $$aSherbenou, D. W.
000164356 700__ $$0245280$$aHantschel, O.$$g209845
000164356 700__ $$aTuraga, L.
000164356 700__ $$aKaupe, I.
000164356 700__ $$aWillis, S.
000164356 700__ $$aBumm, T.
000164356 700__ $$aPress, R. D.
000164356 700__ $$aSuperti-Furga, G.
000164356 700__ $$aDruker, B. J.
000164356 700__ $$aDeininger, M. W.
000164356 773__ $$j22$$k6$$q1184-90$$tLeukemia
000164356 909C0 $$0252328$$pUPHAN$$xU12375
000164356 909CO $$ooai:infoscience.tind.io:164356$$pSV$$particle
000164356 917Z8 $$x182396
000164356 937__ $$aEPFL-ARTICLE-164356
000164356 973__ $$aOTHER$$rREVIEWED$$sPUBLISHED
000164356 980__ $$aARTICLE