Relationship between FLT3 mutation status, biologic characteristics, and response to targeted therapy in acute promyelocytic leukemia by Rosemary E. Gale,

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Presentation transcript:

Relationship between FLT3 mutation status, biologic characteristics, and response to targeted therapy in acute promyelocytic leukemia by Rosemary E. Gale, Robert Hills, Arnold R. Pizzey, Panagiotis D. Kottaridis, David Swirsky, Amanda F. Gilkes, Elizabeth Nugent, Kenneth I. Mills, Keith Wheatley, Ellen Solomon, Alan K. Burnett, David C. Linch, and David Grimwade Blood Volume 106(12):3768-3776 December 1, 2005 ©2005 by American Society of Hematology

Impact of FLT3 mutation status on outcome in APL patients. Impact of FLT3 mutation status on outcome in APL patients. (A) Relapse risk. (B) Overall survival. (C) Relapse risk in patients with APL and non-APLAML. Rosemary E. Gale et al. Blood 2005;106:3768-3776 ©2005 by American Society of Hematology

Hierarchical clustering of genes according to FLT3 status in 26 APL samples. Hierarchical clustering of genes according to FLT3 status in 26 APL samples. The 83 probe sets shown were identified by SAM analysis and represent 78 different genes. Rosemary E. Gale et al. Blood 2005;106:3768-3776 ©2005 by American Society of Hematology

Effect of ATRA and CEP-701 on in vitro growth and differentiation of representative samples. Effect of ATRA and CEP-701 on in vitro growth and differentiation of representative samples. Cells were cultured in RPMI/10% FCS for 3 to 5 days with either nothing further added (Control), 1 μM ATRA, 50 nM CEP-701, or 1 μM ATRA+50 nM CEP-701, and then counted, used in an MTS assay, and immunophenotyped to determine the relative percentage of annexin V–/PI–, CD11b+, and DCFDA+ cells. (A) NB4 cells. (B) Blasts from an FLT3 WT APL patient. (C) Blasts from an FLT3 ITD+ APL patient. Rosemary E. Gale et al. Blood 2005;106:3768-3776 ©2005 by American Society of Hematology

Response to ATRA and CEP-701 in blasts from 6 APL patients. Response to ATRA and CEP-701 in blasts from 6 APL patients. Cells were cultured and assays performed as outlined in Figure 3. Two patients had WT FLT3 (□, ○), and 4 had ITD+ (▪, •, ▴, ♦). Total mutant level was 41% to 48%. One patient (▴) had 3 mutants. Rosemary E. Gale et al. Blood 2005;106:3768-3776 ©2005 by American Society of Hematology