Genomic aberrations in acute myeloid leukemia and significance of constitutional copy number variations in the development of post-transplant lymphoproliferative disorders.

In the first part of this study, 22 AML patients with Normal Karyotype were retrospectively analyzed by using OGT Hematological Cancer 8x60K CGH+ SNP array, in order to detect cryptic genomic aberrations. 11 out of 22 patients confirmed a normal genomic setting;11 out of 22 patients instead showed unexpected genomic imbalances, such as trisomies (+4, +8, +10, +13, +16) or monosomies (-7, -5q, -Y). In addition to this large rearrangements, some patients showed Copy Number Variations (CNVs) containing genes involved in hematological process or tumorigenesis. aCGH was also performed in a small group of patients with Complex karyotype in order to better define the cytogenetic results and to detect cryptic CNVs. This study suggests a potential role for the use of aCGH in the clinical workup of AML patients with Normal karyotype in order to identify cryptic leukemic clones. In the future this new approach will probably permit to better stratify the patients in risk category and make a more appropriate therapy. In the second part of the study,22 renal-transplated patients were tested with OGT Oligoarray platform 4x180K CGH array in order to evaluate constitutional CNVs that might predispose to post-transplant lymphoproliferative disease. Constitutional chromosomal regions involved in genomic imbalances (CNVs) affected mostly regions containing oncogenes or critical hematological regions,such as: 1p21.1,6p25.31, 14q32.33, and 16p11.2. These copy number variations are exclusively described in patients who develop PTLD and patients without PTLD but with High-EBV viral Load, and thus, at risk to develop the disease. This study permitted to identify new candidate loci involved in the predisposition of PTLD-development.