CRLF2. CRLF2- a new player in ALL Ithamar Ganmore, Libi Hertzberg Shai Izraeli’s lab Cancer Research Center, Sheba Medical Center, Tel-Aviv University Israel Society of Hematology and Blood Transfusions annual conference- 16.2.2010. Down syndrome & Leukemia. Chromosome 21 and Leukemia.
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CRLF2- a new player in ALL
Ithamar Ganmore, Libi Hertzberg
Shai Izraeli’s lab
Cancer Research Center, Sheba Medical Center, Tel-Aviv University
Israel Society of Hematology and Blood Transfusions annual conference- 16.2.2010
Down syndrome & Leukemia
Chromosome 21 and Leukemia
Constitutional tirsomy 21
Most cases with 4 copies of chr. 21
AML is on Chr. 21
JAK2 Pseudokinase Domain (Model)
Gilad Wainreb, Nir Ben-Tal
Wild type JAK2
Only with EPOR or TPOR
Hypothesis – constitutional trisomy 21 associated with B linage expression of a type I cytokine receptorcooperating with R683 mutated JAK2
DS-ALLs gene expression profile
From Nature Immunol. 2009; 7: 709–714
Mechanism of abberant CRLF2 expression
Does IL7RA also over-expressed?
Do JAK2 mutations and
CRLF2 over-expression related?
Functional cooperation CRFL2 and JAK2
No requirement for IL7RA
What happen in high CRLF2 without JAK2 mutations?
Mutational screen of CRLF2
F232C- An activating mutation in CRLF2
A model for DS-ALL
(log rank test, p=0.12)
Hertzberg et al Blood 2009
Harvey et al Blood 2010
Yoda et al. PNAS 2009
G te Kronnie
Tel Aviv University
Nir Ben Tal
Support: ISF; WCRF; IL Science and Health Ministries; Wolfoson Foundation; JNF UK