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 2 Constitution of a European Hematological/NGS Platform UNIBO

WP 3 Creation of a biological biobank & clinical Data Warehouse SINAPTICA 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 7 Translation of NGS data on industry applications FASTERIS SA

WP 8 Dissemination & Exploitation UULM

8 Work Packages (WPs) spanning a temporal frame of 36 months

√√

“Cloud” based “avatar” patient information

suitable for home care therapy

Work plan ( first 8 months reports)

WP Number WP Title Lead

beneficiary

WP 1 Management & Coordination UNIBO

WP 2 Constitution of a European Hematological/NGS Platform UNIBO

WP 3 Creation of a biological biobank & clinical Data Warehouse SINAPTICA 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 7 Translation of NGS data on industry applications FASTERIS 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

MDSEZH2IDH1IDH2TET2SF1SF3A1SF3B1U2AF1ASXL1CBLNPM1

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