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: J Immunol. 2004 Sep 15;173(6):3935-44. 

Analysis of Notch1 function by in vitro T cell differentiation of Pax5 mutant
lymphoid progenitors.

Hoflinger S, Kesavan K, Fuxa M, Hutter C, Heavey B, Radtke F, Busslinger M.

Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.

Signaling through the Notch1 receptor is essential for T cell development in the
thymus. Stromal OP9 cells ectopically expressing the Notch ligand Delta-like1
mimic the thymic environment by inducing hemopoietic stem cells to undergo in
vitro T cell development. Notch1 is also expressed on Pax5-/- pro-B cells, which
are clonable lymphoid progenitors with a latent myeloid potential. In this
study, we demonstrate that Pax5-/- progenitors efficiently differentiate in
vitro into CD4+CD8+ alphabeta and gammadelta T cells upon coculture with
OP9-Delta-like1 cells. In vitro T cell development of Pax5-/- progenitors
strictly depends on Notch1 function and progresses through normal developmental
stages by expressing T cell markers and rearranging TCRbeta, gamma, and delta
loci in the correct temporal sequence. Notch-stimulated Pax5-/- progenitors
efficiently down-regulate the expression of B cell-specific genes, consistent
with a role of Notch1 in preventing B lymphopoiesis in the thymus. At the same
time, Notch signaling rapidly induces cell surface expression of the c-Kit
receptor and transcription of the target genes Deltex1 and pre-Talpha
concomitant with the activation of TCR Vbeta germline transcription and the
regulatory genes GATA3 and Tcf1. These data suggest that Notch1 acts upstream of
GATA3 and Tcf1 in early T cell development and regulates Vbeta-DJbeta
rearrangements by controlling the chromatin accessibility of Vbeta genes at the
TCRbeta locus. Copyright 2004 The American Association of Immunologists, Inc.

PMID: 15356142 [PubMed - indexed for MEDLINE]


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3: Cancer Genet Cytogenet. 2004 Aug;153(1):69-72. 

Different gene expression in immunoglobulin-mutated and immunoglobulin-unmutated
forms of chronic lymphocytic leukemia.

Ferrer A, Ollila J, Tobin G, Nagy B, Thunberg U, Aalto Y, Vihinen M, Vilpo J,
Rosenquist R, Knuutila S.

Department of Pathology and Medical Genetics, Haartman Institute, University of
Helsinki, and Helsinki University Central Hospital Laboratory Diagnostics,
Haartmaninkatu 3, FIN-00014 Helsinki, Finland.

The mutation status of the immunoglobulin heavy chain variable regions (IgVH)
has been found to be a good prognostic indicator for B-cell chronic lymphocytic
leukemia (CLL) because unmutated VH genes are associated with rapid disease
progression and shorter survival time. To study the differences in gene
expression between the Ig-unmutated and Ig-mutated CLL subtypes, we performed
gene expression profiling on 31 CLL cases and investigated the VH gene mutation
status by sequencing. The array data showed that the greatest variances between
the unmutated (20 cases) and the mutated (11 cases) group were in expressions of
ZAP70, RAF1, PAX5, TCF1, CD44, SF1, S100A12, NUP214, DAF, GLVR1, MKK6, AF4,
CX3CR1, NAFTC1, and HEX. ZAP70 was significantly more expressed in the
Ig-unmutated CLL group, whereas the expression of all the other genes was higher
in the Ig-mutated cases. These results corroborate a recent finding, according
to which the expression of ZAP70 can predict the VH mutation status and suggest
that RAF1, PAX5, and other differentially expressed genes may offer good markers
for differentiating unmutated cases from mutated cases and thus serve as
prognostic markers.

PMID: 15325098 [PubMed - indexed for MEDLINE]


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