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Blood, 1 September 2008, Vol. 112, No. 5, pp. 2169. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Malek, S. N. Search for Related Content PubMed Articles by Malek, S. N. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CORRESPONDENCE MDM2-SNP 309 allele status does not affect sensitivity to MDM2 inhibitors in CLL We appreciate the rationale for testing MDM2 single nucleotide polymorphism (SNP) 309 status in chronic lymphocytic leukemia (CLL) as a potential predictor of sensitivity to murine double minute 2 (MDM2) inhibitor treatment and for progressive CLL1 as outlined in the letter to the editor by Seyfried et al. We did indeed test our published cohort of CLL cases for SNP309 status using genomic polymerase chain reaction on DNA derived from fluorescence-activated cell sorted CD19+ cells.2 In total, 87 samples without known p53 aberrations (wt p53 exon 5-9 sequence and preserved p53 induction in response to MDM2 inhibitor treatment) were genotyped. As demonstrated in Figure 1, we found no association between MDM2 inhibitor concentration that resulted in 50% apoptosis (IC50 values) and MDM2-SNP309 genotype (allele status TT, TG, or GG). Thus, based on this data in CLL, MDM2 protein levels do not seem to affect MDM2 inhibitor sensitivity. View larger version (15K): [in this window] [in a new window]   Figure 1. Display of mean IC50 values for MDM2-inhibitor-induced CLL apoptosis/necrosis. IC50 values for the MDM2 inhibitors MI-63 (A) and nutlin3 (B): MDM2 inhibitor-mediated CLL cell apoptosis was measured in purified CD19+ cells as described.2 SNP309 genotyping was done using genomic polymerase chain reaction across MDM2 SNP309. Displayed are mean IC50 values grouped by MDM2 SNP309 genotype (TT, TG, GG) and 95% confidence bars.      Authorship Top Authorship References   Conflict-of-interest disclosure: The author declares no competing financial interests. Correspondence: Sami N. Malek, 4312 Cancer Center, 1500 E Medical Center Drive, University of Michigan, Ann Arbor, MI 48109-0640; e-mail: smalek{at}med.umich.edu. Sami N. Malek    References Top Authorship References   Gryshchenko I, Hofbauer S, Stoecher M, et al. MDM2 SNP309 is associated with poor outcome in B-cell chronic lymphocytic leukemia. J Clin Oncol. 2008;26:2252–2257.[Abstract/Free Full Text] Saddler C, Ouillette P, Kujawski L, et al. Comprehensive biomarker and genomic analysis identifies p53 status as the major determinant of response to MDM2 inhibitors in chronic lymphocytic leukemia. Blood. 2008;111:1584–1593.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: SNP309 as predictor for sensitivity of CLL cells to the MDM2 inhibitor nutlin-3a Irina Seyfried, Sebastian Hofbauer, Markus Stoecher, Richard Greil, and Inge Tinhofer Blood 2008 112: 2168. [Full Text] [PDF] Comprehensive biomarker and genomic analysis identifies p53 status as the major determinant of response to MDM2 inhibitors in chronic lymphocytic leukemia Chris Saddler, Peter Ouillette, Lisa Kujawski, Sanjeev Shangary, Moshe Talpaz, Mark Kaminski, Harry Erba, Kerby Shedden, Shaomeng Wang, and Sami N. Malek Blood 2008 111: 1584-1593. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Malek, S. N. Search for Related Content PubMed Articles by Malek, S. N. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?

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