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High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated.

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Presentation on theme: "High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated."— Presentation transcript:

1 High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated by Sanne Lugthart, Ellen van Drunen, Yvette van Norden, Antoinette van Hoven, Claudia A. J. Erpelinck, Peter J. M. Valk, H. Berna Beverloo, Bob Löwenberg, and Ruud Delwel Blood Volume 111(8): April 15, 2008 ©2008 by American Society of Hematology

2 Gene structure and primer/probe locations of EVI1 splice variants -1A, -1B, -1C, -1D, -3L, and MDS1/EVI1 (ME). Gene structure and primer/probe locations of EVI1 splice variants -1A, -1B, -1C, -1D, -3L, and MDS1/EVI1 (ME). The exons, introns, and translational starts are depicted in boxes, connective lines, and standup arrows, respectively. The first exon's size in base pairs (bp), primers (arrows), and probes (bold line) are shown. Nucleotide sequences of primer/probe are presented in Table S1. Sanne Lugthart et al. Blood 2008;111: ©2008 by American Society of Hematology

3 EVI1 mRNA expression levels in EVI1-1D+ and EVI1-1D− AML samples in cohort A and B determined by Northern blot. EVI1 mRNA expression levels in EVI1-1D+ and EVI1-1D− AML samples in cohort A and B determined by Northern blot. Human 600-bp EVI1 probe and as control a murine GAPDH fragment were used. Patients I and II represent AML samples without EVI1 expression. The patient numbers correspond to those in Table 1. Sanne Lugthart et al. Blood 2008;111: ©2008 by American Society of Hematology

4 High EVI1 expression associates with poor survival outcome in AML
High EVI1 expression associates with poor survival outcome in AML. Kaplan Meier analysis of (A) overall survival (OS), (B) event-free survival (EFS), and (C) disease-free survival (DFS) shows an inferior outcome for EVI1+ patients in comparison with patient... High EVI1 expression associates with poor survival outcome in AML. Kaplan Meier analysis of (A) overall survival (OS), (B) event-free survival (EFS), and (C) disease-free survival (DFS) shows an inferior outcome for EVI1+ patients in comparison with patients without EVI1 overexpression in a total cohort of 534 AML patients. Sanne Lugthart et al. Blood 2008;111: ©2008 by American Society of Hematology

5 Fluorescent in situ hybridization (FISH) of chromosome 3q26 and 3q21 loci reveal hidden 3q26 aberrations. Fluorescent in situ hybridization (FISH) of chromosome 3q26 and 3q21 loci reveal hidden 3q26 aberrations. BAC clone localization from centromere (Cen) to telomere (Tel) (A). A metaphase from EVI1+ patient no. 28 revealed a cryptic inv(3)(q21q26) (inv3) and a normal chromosome 3 (nor3) using EVI1 (RP11-82C9) and MDS1 (RP11-141C22) (B) and RPN1 (RP11-456K4) BAC clones (C). Micrographs after FISH were acquired by imaging with a fluorescence microscope (Axio-Imager Z1; Zeiss, Sliedrecht, The Netherlands) fitted with a Plan-Apochromat at 100x/1.40 numeric aperture oil objective, a CCD video camera (Metasystems, Altlussheim, Germany), and using Isis software for capturing and processing fluorescent images (v5.1.7, Metasystems). Sanne Lugthart et al. Blood 2008;111: ©2008 by American Society of Hematology

6 Inferior outcome for EVI1+ME− patients in comparison with EVI1+ME+ patients.
Inferior outcome for EVI1+ME− patients in comparison with EVI1+ME+patients. Kaplan Meier analysis of (A) overall survival (OS) and (B) event-free survival (EFS) shows an inferior outcome for EVI1+ME− patients in comparison with EVI1+ME+ patients in the cohort of 41 EVI1+ AML patients. Sanne Lugthart et al. Blood 2008;111: ©2008 by American Society of Hematology


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