Personalized medicine in
hematological malignancies:
a new horizon
Giovanni Martinelli
University of Bologna
(UNIBO)
Institute of Hematology
and Medical Oncology
“L. e A. Seragnoli”
Bologna Italy
as EHA representative
ECCO-ESMO-ESTRO Congress
Amsterdam
29th September
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?
The personalized “avatar”
“Avatar”
Diagnosis: es. BCR-ABL1 like ALL
for each haematological patient to get right target
therapy, in a correct dosage, (possible at home)
1 week work = “molecular make up”
Genome Analyzer II (Illumina/Solexa)/Roche 454
reads for each
gene
CURE
diagnosis
relapse
RNA/DNA
Simulation or
Extra Rapid (mins not months)
Computer assisted decision,
Bioinformatics NGS analysis
in vitro identification of new drugs, etc.
( e.g. KNOME analysis)
Design and apply experimental “individual”
done by a medical doctor
and personalized
“Back to bed, soon”
clinical trial
(need regulatory EMEA changes 1 day
) work
Individual new therapy
Old therapy combined
with new (eg.TKI) therapy
Old Classic therapy +
?
(ex. Tki, Antibiotic, Vitamin,..)
Individual New Target(s)
The NGS-PTL project:
Project details
 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)
Partners
Katholieke Universiteit Leuven
(KU Leuven)
Belgium
Personal Genomics SRL
Italy
Muenchner LeukaemiaLabor GmbH
(MLL)
Germany
Masarykova Univerzita (MU)
Czech Republic
FASTERIS SA
Switzerland
University of ULM (UULM)
Germany
University of Bologna (UNIBO)
Italy
Fundacion De Investigacion Del Cancer De La
Universidad De Salamanca (FICUS)
Spain
SINAPTICA IT SRL
Italy
5 academic partners + 5 SMEs
University of Turin (UNITO)
Italy
Objectives
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 patients
3. To provide out come therapies (home sweet home)
Work plan
8 Work Packages (WPs) spanning a temporal frame of 36 months
WP
Number
WP 1
WP 2
WP 3
WP 4
WP 5
WP 6
WP 7
WP 8
WP Title
Management & Coordination
Constitution of a European
Hematological/NGS Platform
Creation of a biological biobank &
clinical Data Warehouse
Identification of novel mutations &
molecular profiles by exome
and/or transcriptome NGS
Screening of point mutations in
candidate gene targets by
amplicon NGS & DNA enrichment
approach
Identification of bone marrow &
circulating miRNA and their
association with clinical outcome
Translation of NGS data on
industry applications
Dissemination & Exploitation
Lead
beneficiary
UNIBO
UNIBO
SINAPTICA IT
Personal
Genomics
MLL
UNITO
FASTERIS SA
UULM
√
√
“Cloud” based
“avatar” patient information
suitable for home care therapy
Work plan
( first 8 months reports)
8 Work Packages (WPs) spanning a temporal frame of 36 months
WP
Number
WP 1
WP 2
WP 3
WP 4
WP 5
WP 6
WP 7
WP 8
WP Title
Management & Coordination
Constitution of a European
Hematological/NGS Platform
Creation of a biological biobank &
clinical Data Warehouse
Identification of novel mutations &
molecular profiles by exome
and/or transcriptome NGS
Screening of point mutations in
candidate gene targets by
amplicon NGS & DNA enrichment
approach
Identification of bone marrow &
circulating miRNA and their
association with clinical outcome
Translation of NGS data on
industry applications
Dissemination & Exploitation
Lead
beneficiary
UNIBO
UNIBO
SINAPTICA IT
Personal
Genomics
MLL
UNITO
FASTERIS SA
UULM
√
√
√
√
200 Acute Myeloid leukemia
150 Acute Lymphoblastic Leukemia
130 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.
Diagnostics
Screening, follow-up, clonal evolution, drug-resistance,
risk-assessment,
etc…..
The future:
CIRCULAR DNA
ON BLOOD
Gene/s
candidate
Discovery
Next Generation
Sequencing
and identification
of genetic
Landscape
of Somatic
Mutations
in Hema Neoplasms
defect and possible target for personalized therapy
CLL Leukemia
Multiple Myeloma
TP53
B-RAF
Cell
Leukemia
B-Raf
Next
Generation
Sequencing
MDS
EZH2
IDH1
IDH2
TET2
SF1
SF3A1
SF3B1
U2AF1
ASXL1
CBL
NPM1
TP53
NOTCH1 (PEST)
SF3B1 (HEAT)
FBXW7
MYD88
Hairy
XPO1
Myeloprolipherative
Disease and PhTP53
EZH2
IDH1
IDH2
TET2
CBL
KRAS
Acute Myeloid
Leukemia
CML and Acute
Lymphoblastic
Leukemia
TP53
NOTCH1
FBXW7
IKZF1
BCR-ABL
IL7R
CRLF2
TP53
IDH1/IDH2
EZH2
DNMT3A
CEBPA
CBL
KRAS
TET2
RUNX1
BCOR
PML-RAR alpha