PS1020 SNP ARRAY REVEALS A NEW DELETION OF JAK2 IN AML PATIENTS
Authors: C. Cerchione, V. Guadagnuolo, C. Papayannidis, M.C. Fontana, A. Padella, I. Iacobucci, G. Simonetti, G. Marconi, S. Paolini, M. Abbenante, S. Parisi, F. Volpato, E. Ottaviani, M. Delledonne, G. Biasco, G. Martinelli
Journal: HemaSphere (2019)

Background: Acute Myeloid Leukemia (AML) is a disease of the elderly that initiates in a hematopoietic stem cell and is characterized by clonal hematopoiesis and uncertain prognosis, mostly due to cytogenetic background. Aims: In Acute Myeloid Leukemia (AML) there is a strong need to develop new diagnostic and therapeutic options: to identify the genes mostly predictive of treatment response, we use Single Nucleotide Polymorphism (SNP) Arrays and Whole Exome Sequencing (WES) in AML patients with heterogeneous karyotypes and different subgroups. Methods: SNP arrays (CytoScan HD Array, Affymetrix Inc.) was positively done in 58 AML samples and all of them were analyzed by Chromosome Analysis Suite (ChAS) v1.2 (Affymetrix Inc.) and Nexus Copy Number™ v7.5 software (BioDiscovery), while Next Generation Sequencing (NGS)‐WES HiSeq 2000 (Illumina) was done in 35 AML patients. Results: We treated 58 AML patients (pts) with a median age of 52 years, of which 9 were insensitive pts and 49 sensitive to therapies, all obtaining complete clinical remission. Copy Number Alterations (CNAs) were detected in all patients affecting all the chromosomes, in particular our cohort of pts present a percentage of CNA, divided as follow: 58% of LOH, 15% of gain, 16% of loss, 3% of high copy gain and 4% of homozygous copy loss. We found that several cancer genes were preferentially amplified: IGH@, KIT, IGL@, TSC1, NOTCH2, SETD2, EZH2, while in high copy gain we found TSC1, PTEN, RB1, IKZF1, ZRSR2, IGH@, NF1, MYC, KRAS. Then several genes were preferentially deleted: CRLF2, ATRX, JAK2, BCOR, PHF6, GATA1, KDM6A and in homozygous copy loss: JAK2, CRLF2, RB1, PDGFRA, RUNX1. Moreover we genes in LOH: DDX5, MTCP1, HOOK3, ZRSR2, GATA1, KDM6A, BCOR, NF1, BRAF, ATRX. We focused on two losses of JAK2: the first deletion, detected in 18/58 (31%) pts, goes from 5030 to 5038 Kbp (7,43 Kbps) including intron 4–5; the second minimal common region of loss, detected in 5/58 (8,6%) pts, goes from 5083 to 5098 Kpb (15 Kbps) including intron 19–20 and exons 20, 21 and 22, suggesting a defective transduction, in fact we showed that the overall survival rate is better for the group of pts which present a deletion of JAK2 rather than the group with an amplification of this gene (p‐value &lt;0,01). We have also found three other genes which are preferentially lost: SIRPB1, ADAM3A and STAG2 with a percentage of 50%, 43% and 69% respectively. By NGS‐WES we analyzed 35 AML samples at diagnosis and we searched for point mutations, insertion/deletion or other abnormalities, involved in biomarkers of response to treatment. We found mutations in SF3B1, NPM1, CBL, RUNX1, BCOR, KIT, GATA2, IDH2, KDM6A, KIAA1324L, PRIM2, RRN3, APOBR. Summary/Conclusion: By SNP arrays we have identified Copy Number Alterations involving important cancer genes AML and we showed that a new deletion in JAK2 may have a role in overall survival rate. Future prospective will be to correlate the cancer genes alteration and mutations with the prognosis of AML, in order to identify new biomarkers relevant for the disease.