Genome-wide Profiling in AML Patients Relapsing after Allogeneic Hematopoietic Cell Transplantation  Miguel Waterhouse, Dietmar Pfeifer, Milena Pantic,

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Genome-wide Profiling in AML Patients Relapsing after Allogeneic Hematopoietic Cell Transplantation  Miguel Waterhouse, Dietmar Pfeifer, Milena Pantic, Florian Emmerich, Hartmut Bertz, Jürgen Finke  Biology of Blood and Marrow Transplantation  Volume 17, Issue 10, Pages 1450-1459.e1 (October 2011) DOI: 10.1016/j.bbmt.2011.07.012 Copyright © 2011 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 Posttransplant deletion on chromosome 13q12, resulting in a zygosity change in FLT3-ITD mutational status. Copy number profile of chromosome 13 in patient #17 using 250k NspI SNP mapping arrays. Pretransplant sample is represented in green, while leukemic blast at relapse is represented in blue (A). A log-2 ratio reduction of 17 Mb, between 13q12.2 and 13q14.11 spanning the FLT3 locus (red line) was detected in the posttransplant sample indicating a deletion as depicted by the copy number change. FLT3-ITD mutational status change after transplantation (B). Wild-type allele was always detected at approximately 129 bp, whereas the FLT3-ITD mutated allele varied in size from 140 bp to 240 bp. Heterozygous FLT3-ITD mutation detected in the pretransplant sample, wild-type peak is more than 50% higher than the mutated allele. After transplantation a loss of almost the whole wild-type peak is detected, resulting in homozygosity for FLT3-ITD mutation. Biology of Blood and Marrow Transplantation 2011 17, 1450-1459.e1DOI: (10.1016/j.bbmt.2011.07.012) Copyright © 2011 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Loss of mismatched HLA on leukemic blasts from patient #14 is because of CN-LOH on chromosome 6p and was confirmed by sequencing of HLA-A∗ gene. Copy number and LOH profiles of chromosome 6 in patient #14 using SNP 6.0 mapping arrays. Pretransplant sample is represented in green, while leukemic blast at relapse is represented in blue (A). Genome-wide analysis of isolated leukemic cells revealed a 40 Mb loss of heterozygous SNPs (red square) on chromosome 6p, with the normal copy number, spanning the whole HLA locus (in yellow). Partial sequence of the exon 2 of HLA-A gene (B). Heterozygous positions (249-264) in patient sequence at the time of diagnosis, and in the donor sequence. Patient sequence in leukemic blasts at the time of relapse shows loss of 1 allele resulting in homozygosity of the corresponding sequence. Biology of Blood and Marrow Transplantation 2011 17, 1450-1459.e1DOI: (10.1016/j.bbmt.2011.07.012) Copyright © 2011 American Society for Blood and Marrow Transplantation Terms and Conditions