LSC CLL

Leukemic Stem Cells in Chronic Lymphocytic Leukemia

Coordinatore	FONDAZIONE CENTRO SAN RAFFAELE DEL MONTE TABOR    more  Organization address address: Via Olgettina 60 city: MILANO postcode: 20132 contact info Titolo: Mr. Nome: Mario Cognome: Valsecchi Email: send email Telefono: +39 02 2643 2729 Fax: +39 02 2643 2752
Nazionalità Coordinatore	Italy [IT]
Totale costo	75˙000 €
EC contributo	75˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2010-RG
Funding Scheme	MC-IRG
Anno di inizio	2010
Periodo (anno-mese-giorno)	2010-10-01   -   2013-09-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	FONDAZIONE CENTRO SAN RAFFAELE DEL MONTE TABOR  Organization address address: Via Olgettina 60 city: MILANO postcode: 20132 contact info Titolo: Mr. Nome: Mario Cognome: Valsecchi Email: send email Telefono: +39 02 2643 2729 Fax: +39 02 2643 2752	IT (MILANO)	coordinator	75˙000.00

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 Obiettivo del progetto (Objective)

'B cell Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in western countries. Although substantial therapeutic improvements have been obtained, the disease is incurable and causes 4000 deaths/year in the sole USA. We plan to in vivo evaluate CLL B cells division by measuring Deuterium (2H) incorporation into newly synthesized DNA. 2H given to patients in the form of deuterated water (2H2O) is a very practical, safe, non invasive approach that has been already exploited in CLL patients. Preliminary data obtained in 15 CLL patients using the 2H labeling approach are showing in each CLL clone two sub-populations that have 10 times different proliferation rates and can be identified using two well known surface markers, CXCR4 and CD5. The data also indicate that isolated resting cells express higher mRNA for genes found in hematopoietic stem cells (HSC) such as ABCB1, ABCB4 and Notch1. On the other hand proliferating cells express higher levels of known activation markers some of which (CD38, CD52, CD23, others) are target of monoclonal antibodies already in use. We want to refine the description of proliferating and resting cells within each clone by running a more extended immunophenotype and gene expression profile. The detailed description of highly resting and highly proliferating cells will provide new insights of the biology of the disease and a powerful tool for developing drugs aimed at target these fractions with high specificity. Moreover, RAG2-/-yc-/- mice will be used to test if highly defined resting and proliferating cells differ in their capacity to recapitulate the tumor. This mouse background has been successfully used for reconstituting a human hematopoietic system by transferring CD34 cells and was found to support with high efficiency expansion of the CLL cell line MEC-1. We expect to find CLL resting cells to have a higher potential to recapitulate the tumor in mice model providing the first proof of a Leukemic Stem Cell in CLL'