University of Bologna(UNIBO)
Institute of Hematology and Medical Oncology
“L. e A. Seragnoli” Bologna Italy
Giovanni Martinelli
as EHA representative ECCO-ESMO-ESTRO Congress
Amsterdam 29th September
Personalized medicine in hematological malignancies:
a new horizon
Road map of my perspective
The NGS-PTL project:“From patients genomes, in few days, to be able to set up a individualized target therapy” with information by snps
array, transcriptome-GEP and NGS thus providing for each “hematological” patients an “avatar” with
pharmaco-genomic information, and providing targets suitable to personalized THERAPY.
• The 'state of the art' in haematological personalized medicine research
• Why a need to support haematological research?
reads for each gene
“Avatar” Diagnosis: es. BCR-ABL1 like ALL
diagnosisrelapse
RNA/DNA
Genome Analyzer II (Illumina/Solexa)/Roche 454
Old Classic therapy + ?(ex. Tki, Antibiotic, Vitamin,..)
Individual new therapy Old therapy combined with new (eg.TKI) therapy
1 week work = “molecular make up”
Individual New Target(s)
Extra Rapid (mins not months) Bioinformatics NGS analysis
( e.g. KNOME analysis)done by a medical doctor
“Back to bed, soon”
1 day work
The personalized “avatar” for each haematological patient to get right target
therapy, in a correct dosage, (possible at home)
CURESimulation or
Computer assisted decision, in vitro identification of new drugs, etc.
Design and apply experimental “individual” and personalized
clinical trial (need regulatory EMEA changes )
Title: "Next Generation Sequencing platform for targeted Personalized Therapy of Leukemia“
Acronym: NGS-PTL
Grant agreement: n. 306242
Call identifier: FP7-HEALTH-2012-INNOVATION-1
Funding scheme: Collaborative project
EC contribution: 5,870,815 €
Duration: 3 years (starting date: 1-11-2012)
The NGS-PTL project: Project details
University of Turin (UNITO)Italy
University of Bologna (UNIBO) Italy
SINAPTICA IT SRLItaly
Katholieke Universiteit Leuven(KU Leuven)
Belgium
University of ULM (UULM) Germany
Masarykova Univerzita (MU)Czech Republic
FASTERIS SA Switzerland
Personal Genomics SRL Italy
Fundacion De Investigacion Del Cancer De La Universidad De Salamanca (FICUS)
Spain
Muenchner LeukaemiaLabor GmbH (MLL)
Germany
Partners
5 academic partners + 5 SMEs
1. To develop a European Hematological/NGS network of physicians and scientists.
2. To discover novel insights into the mechanisms involved in leukemogenesis and to develop genetic models that accurately define novel leukemia subtypes based on the genomic profile of individual patients.
3. To develop biostatistic and bioinformatic tools for coupling genomic data with clinical/molecular ones.
4. To develop “leukemia diagnostic panels” to drive personalized treatments and tailor therapies:
1. To different stratified groups of leukemia patients. 2. To treat elderly and unfit patients3. To provide out come therapies (home sweet home)
Objectives
Work plan
WP Number
WP Title Lead
beneficiary
WP 1 Management & Coordination UNIBO
WP 2Constitution of a European
Hematological/NGS PlatformUNIBO
WP 3Creation of a biological biobank &
clinical Data WarehouseSINAPTICA IT
WP 4Identification of novel mutations &
molecular profiles by exome and/or transcriptome NGS
Personal Genomics
WP 5
Screening of point mutations in candidate gene targets by
amplicon NGS & DNA enrichment approach
MLL
WP 6Identification of bone marrow &
circulating miRNA and their association with clinical outcome
UNITO
WP 7Translation of NGS data on
industry applicationsFASTERIS SA
WP 8 Dissemination & Exploitation UULM
8 Work Packages (WPs) spanning a temporal frame of 36 months
√√
Work plan ( first 8 months reports)
WP Number
WP Title Lead
beneficiary
WP 1 Management & Coordination UNIBO
WP 2Constitution of a European
Hematological/NGS PlatformUNIBO
WP 3Creation of a biological biobank &
clinical Data WarehouseSINAPTICA IT
WP 4Identification of novel mutations &
molecular profiles by exome and/or transcriptome NGS
Personal Genomics
WP 5
Screening of point mutations in candidate gene targets by
amplicon NGS & DNA enrichment approach
MLL
WP 6Identification of bone marrow &
circulating miRNA and their association with clinical outcome
UNITO
WP 7Translation of NGS data on
industry applicationsFASTERIS SA
WP 8 Dissemination & Exploitation UULM
8 Work Packages (WPs) spanning a temporal frame of 36 months
√√√ 200 Acute Myeloid leukemia
150 Acute Lymphoblastic Leukemia130 CLL>600 hema disease..√
The 'state of the art' in haematological personalized
medicine research
Hematopathology has advanced in parallel with technological developments that have expanded our understanding of the phenotypic, genetic, and molecular characteristics of the hematological neoplasms.
Discovery
Gene/s candidate
Screening, follow-up, clonal evolution, drug-resistance, risk-assessment, etc…..
Diagnostics
The future:CIRCULAR DNA ON BLOOD
Next Generation Sequencing
Next Generation Sequencing and identification of genetic defect and possible target for personalized therapy
CML and Acute Lymphoblastic
LeukemiaTP53NOTCH1FBXW7IKZF1BCR-ABLIL7RCRLF2
Acute Myeloid Leukemia
TP53IDH1/IDH2EZH2DNMT3ACEBPACBLKRASTET2RUNX1BCOR
PML-RAR alpha
MDS
EZH2IDH1IDH2TET2SF1SF3A1SF3B1U2AF1ASXL1CBLNPM1
Myeloprolipherative Disease and Ph-
TP53EZH2IDH1IDH2TET2CBLKRAS
TP53NOTCH1 (PEST)SF3B1 (HEAT)FBXW7MYD88XPO1
Multiple MyelomaTP53B-RAF
Hairy Cell Leukemia
B-Raf
Landscape of Somatic Mutations in Hema Neoplasms
CLL Leukemia