SNP ARRAY REVEALS A NEW DELETION OF JAK2 IN AML PATIENTS
Author(s): ,
Claudio Cerchione
Affiliations:
Hematology Unit,Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS,Meldola (FC),Italy
,
Viviana Guadagnuolo
Affiliations:
Hematology,'L. e A. Seragnoli' University of Bologna,Bologna,Italy
,
Cristina Papayannidis
Affiliations:
Hematology,'L. e A. Seragnoli' University of Bologna,Bologna,Italy
,
Maria Chiara Fontana
Affiliations:
Hematology,'L. e A. Seragnoli' University of Bologna,Bologna,Italy
,
Antonella Padella
Affiliations:
Hematology,'L. e A. Seragnoli' University of Bologna,Bologna,Italy
,
Ilaria Iacobucci
Affiliations:
Hematology,'L. e A. Seragnoli' University of Bologna,Bologna,Italy
,
Giorgia Simonetti
Affiliations:
Hematology Unit,Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS,Bologna,Italy
,
Giovanni Marconi
Affiliations:
Hematology,'L. e A. Seragnoli' University of Bologna,Bologna,Italy
,
Stefania Paolini
Affiliations:
Hematology,'L. e A. Seragnoli' University of Bologna,Bologna,Italy
,
Mariachiara Abbenante
Affiliations:
Hematology,'L. e A. Seragnoli' University of Bologna,Bologna,Italy
,
Sarah Parisi
Affiliations:
Hematology,'L. e A. Seragnoli' University of Bologna,Bologna,Italy
,
Francesca Volpato
Affiliations:
Hematology,'L. e A. Seragnoli' University of Bologna,Bologna,Italy
,
Emanuela Ottaviani
Affiliations:
Hematology,'L. e A. Seragnoli' University of Bologna,Bologna,Italy
,
Massimo Delledonne
Affiliations:
Hematology,'L. e A. Seragnoli' University of Bologna,Bologna,Italy
,
Guido Biasco
Affiliations:
Hematology,'L. e A. Seragnoli' University of Bologna,Bologna,Italy
Giovanni Martinelli
Affiliations:
Hematology Unit,Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS,Meldola (FC),Italy
EHA Library. CERCHIONE C. Jun 15, 2019; 266637; PS1020
Claudio CERCHIONE
Claudio CERCHIONE
Contributions
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Abstract

Abstract: PS1020

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

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 < 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.

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.

Session topic: 3. Acute myeloid leukemia - Biology & Translational Research

Keyword(s): Acute myeloid leukemia, Chromosomal abnormality, Gene expression profile, SNP

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