SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

T U M O R I M M U N O L O G Y P R O G R A M
lated by an intricate network of genes. Through a
comprehensive gene expression analysis during
stem cell differentiation, Dr. Jurecic and his colleagues
have identified a novel evolutionarily conserved
RING finger protein FLRF (Rnf41).
During blood cell development, FLRF (fetal liver
ring finger) acts as an E3 ubiquitin ligase and affects
proliferation and differentiation of HSC and
multipotent progenitors by regulating cytokine
receptor levels through ligand independent degradation.
By regulating steady-state levels of
cytokine receptors, FLRF could be maintaining
optimal signaling for a proper cellular response
(proliferation, lineage commitment, differentiation)
of HSC and progenitors, while preventing
oversignaling that could lead to leukemogenesis.
Developmental Biology and Plasticity of
Hematopoietic Stem Cells
HSC may have the capacity to develop into cells
of unrelated tissue(s). This discovery could have
important implications for designing new stem
cell transplantation and cell therapy protocols for
treatment of various diseases. The aim of this
project is to analyze whether HSC possess the
potential for differentiation into cell types other
than that of blood lineages. To study the full developmental
potential of HSC, Dr. Jurecic’s laboratory
has developed a new in utero stem cell
transplantation assay, named blastocyst engraftment
assay (BEA). BEA is based on microinjection
of purified HSC into mouse preimplantation
embryos (blastocysts), similar to embryonic stem
(ES) cell technology. Using BEA, they have demonstrated
that microinjected transgenic HSC successfully
engraft fetal hematopoietic tissues (yolk
sac, fetal liver). They also obtained preliminary
evidence that mouse adult HSC have the capacity
to develop into fetal central nervous system
(CNS) and heart muscle cells. If adult HSC can
indeed develop into functional cells from unrelated
tissues, this would permit the possibility of
using autologous HSC to treat disorders affecting
various tissues.
SELECTED PUBLICATIONS
2002
Chen, AJ, Zhou, G, Juan, T, Colicos, SM, Cannon,
JP, Cabriera-Hansen, M, Meyer, CF, Jurecic,
R, Copeland, NG, Gilbert, DJ, Jenkins, NA,
Fletcher, F, Tan, TH, and Belmont, JW. The dual
specificity JKAP specifically activates the c-Jun
N-terminal kinase pathway. Journal of Biological
Chemistry 277:36592-601, 2002.
Spassov, DS and Jurecic, R. Cloning and comparative
sequence analysis of PUM1 and PUM2
genes, human members of the Pumilio family of
RNA-binding proteins. Gene 299:195-204,
2002.
2003
Spassov, DS and Jurecic, R. Mouse Pum1 and
Pum2 genes, members of the Pumilio family of
RNA-binding proteins, show differential expression
in fetal and adult hematopoietic stem cells
and progenitors small star, filled. Blood Cells,
Molecules and Diseases 30:55-69, 2003.
Komatsu, M, Mammolenti, M, Jones, M,
Jurecic, R, Sayers, TJ, and Levy, RB. Antigenprimed
CD8+ T cells can mediate resistance, preventing
allogeneic marrow engraftment in the
simultaneous absence of perforin-, CD95L-,
TNFR1-, and TRAIL-dependent killing. Blood
101:3991-99, 2003.
Spassov, DS and Jurecic, R. The PUF family of
RNA-binding proteins: does evolutionarily
conserved structure equal conserved function?
IUBMB Life 55: 359-66, 2003.
Liang, H, Chen, Q, Coles, AH, Anderson, SJ,
Pihan, G, Bradley, A, Gerstein, R, Jurecic, R, and
Jones, SN. Wnt5a inhibits B cell proliferation
and functions as a tumor suppressor in hematopoietic
tissue. Cancer Cell 4:349-60, 2003.
UM/Sylvester Comprehensive Cancer Center Scientific Report 2004 109