1: Hum Cell. 2004 Jun;17(2):85-92. 

Transcription factor expression in cell lines derived from natural killer-cell
and natural killer-like T-cell leukemia-lymphoma.

Matsuo Y, Drexler HG, Harashima A, Okochi A, Shimizu N, Orita K.

Fujisaki Cell Center, Hayashibara Biochemical Labs, Okayama 702-8006, Japan.
yomatsuo@hayashibara.co.jp

Although a number of transcription factors (TFs) have been identified that play
a pivotal role in the development of hematopoietic lineages, only little is
known about factors that may influence development and lineage commitment of
natural killer (NK) or NK-like T (NKT)-cells. Obviously to fully appreciate the
NK- and NKT-cell differentiation process, it is important to identify and
characterize the TFs effecting the NK- and NKT-cell lineage. Furthermore, these
TFs may play a role in NK- or NKT-cell leukemias, in which the normal
differentiation program is presumably disturbed. The present study analyzed the
expression of the following 13 TFs: AML1, CEBPA, E2A, ETS1, GATA1, GATA2, GATA3,
IKAROS, IRF1, PAX5, PU1, TBET and TCF1 in 7 malignant NK-cell lines together
with 5 malignant NKT-cell lines, 5 T-cell acute lymphoblastic leukemia (ALL)
cell lines including 3 gamma/delta T-cell receptor (TCR) type and 2 alpha/beta
TCR type, and 3 B-cell precursor (BCP) leukemia cell lines. AML1, E2A, ETS1,
IKAROS and IRF1 were found to be positive for all cell lines tested whereas
GATA1 turned out to be universally negative. CEBPA, PAX5 and PU1 were negative
for all cell lines tested except in the three positive BCP-cell lines. GATA2 was
positive for 3/5 T-cell lines but negative for the other cell lines. GATA3 was
positive for 7/7 NK-, 4/5 NKT-, 5/5 T- and 2/3 BCP-cell lines. TBET was positive
for all NK- and NKT-cell lines and negative for all T- and BCP-cell lines except
one BCP-cell line. In contrast to the expression of TBET, TCF1 was negative for
all NK- and NKT-cell lines, being positive for 4/5 T- and 1/3 BCP-cell lines.
Expression analysis of TFs revealed that NK- and NKT-cell lines showed identical
profiles, clearly distinct from those of the other T-ALL or BCP-ALL
leukemia-derived cell lines..

PMID: 15369140 [PubMed - indexed for MEDLINE]


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2: EMBO J. 2003 Aug 1;22(15):3887-97. 

Myeloid lineage switch of Pax5 mutant but not wild-type B cell progenitors by
C/EBPalpha and GATA factors.

Heavey B, Charalambous C, Cobaleda C, Busslinger M.

Research Institute of Molecular Pathology, Vienna Biocenter,Dr. Bohr-Gasse 7,
A-1030 Vienna, Austria.

The developmental potential of hematopoietic progenitors is restricted early on
to either the erythromyeloid or lymphoid lineages. The broad developmental
potential of Pax5(-/-) pro-B cells is in apparent conflict with such a strict
separation, although these progenitors realize the myeloid and erythroid
potential with lower efficiency compared to the lymphoid cell fates. Here we
demonstrate that ectopic expression of the transcription factors C/EBPalpha,
GATA1, GATA2 and GATA3 strongly promoted in vitro macrophage differentiation and
myeloid colony formation of Pax5(-/-) pro-B cells. GATA2 and GATA3 expression
also resulted in efficient engraftment and myeloid development of Pax5(-/-)
pro-B cells in vivo. The myeloid transdifferentiation of Pax5(-/-) pro-B cells
was accompanied by the rapid activation of myeloid genes and concomitant
repression of B-lymphoid genes by C/EBPalpha and GATA factors. These data
identify the Pax5(-/-) pro-B cells as lymphoid progenitors with a latent myeloid
potential that can be efficiently activated by myeloid transcription factors.
The same regulators were unable to induce a myeloid lineage switch in Pax5(+/+)
pro-B cells, indicating that Pax5 dominates over myeloid transcription factors
in B-lymphocytes.

PMID: 12881423 [PubMed - indexed for MEDLINE]


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