1: Leuk Res. 2004 Nov;28(11):1227-37. 

Analysis of the relationship between Scl transcription factor complex protein
expression patterns and the effects of LiCl on ATRA-induced differentiation in
blast cells from patients with acute myeloid leukemia.

Rice AM, Holtz KM, Karp J, Rollins S, Sartorelli AC.

Department of Pharmacology, Cancer Center, Yale University School of Medicine,
333 Cedar Street, New Haven, CT 06520, USA.

Exogenous expression of the transcription factor Scl (Tal1) in WEHI-3B D+
myelomonocytic leukemia cells interferes with their capacity to respond to
all-trans retinoic acid (ATRA) induced differentiation; combination of ATRA with
LiCl, however, circumvents the inhibition of differentiation produced by Scl. To
gain information on the possible involvement of this transcription factor in the
non-responsiveness of acute myelocytic leukemia (AML) patients to ATRA, we
compared the endogenous expression levels of Scl and its transcription complex
partners [i.e., Rbtn1 (LMO1), Rbtn2 (LMO2), Ldb1, and GATA family proteins] in
leukemic blast cells from patients with AML and acute promyelocytic leukemia
(APL), and determined the effects of lithium chloride alone or in combination
with ATRA on the capacity of blast cells to differentiate during short-term ex
vivo culture. Levels of Scl, Rbtn2, GATA1, and Ldb1 expression were comparable
in AML and APL blasts, while the levels of expression of Rbtn1, GATA2, and GATA3
were absent or markedly lower in APL cells. Differentiation markers (cell
surface myeloid antigens CD11b, CD15, CD14, and CD33) were also analyzed in
blast cells. ATRA produced changes in at least one surface antigen
differentiation marker in 89% of patient blasts, while LiCl caused such changes
in 72% of the leukemic cells of patients. The combination of LiCl and ATRA
induced the differentiation of leukemic blasts from 94% of patients. Although
the expression of the transcription factors did not act as individual predictors
of responsiveness or non-responsiveness to the inducers of differentiation, ATRA
or ATRA plus LiCl, the addition of LiCl to ATRA increased the differentiation
response over that of ATRA alone in a number of leukemic samples. These findings
suggest that the combination of LiCl and ATRA may produce some clinical benefit
in the treatment of the myeloid leukemias.

PMID: 15380350 [PubMed - indexed for MEDLINE]


---------------------------------------------------------------


2: Development. 2000 Feb;127(3):643-53. 

Lmo2 and GATA-3 associated expression in intraembryonic hemogenic sites.

Manaia A, Lemarchandel V, Klaine M, Max-Audit I, Romeo P, Dieterlen-Lievre F,
Godin I.

Institut d'Embryologie Cellulaire et Moleculaire du CNRS et du College de
France; 49bis, av. de la Belle Gabrielle, France.

It is now widely accepted that hemopoietic cells born intraembryonically are the
best candidates for the seeding of definitive hemopoietic organs. To further
understand the mechanisms involved in the generation of definitive hemopoietic
stem cells, we analysed the expression of the hemopoietic-related transcription
factors Lmo2 and GATA-3 during the early steps of mouse development (7-12 dpc),
with a particular emphasis on intraembryonic hemogenic sites. We show here that
both Lmo2 and GATA-3 are present in the intraembryonic regions known to give
rise to hemopoietic precursors in vitro and in vivo, suggesting that they act
together at key points of hemopoietic development. (1) Lmo2 and GATA-3 are
expressed in the caudal mesoderm during the phase of intraembryonic precursors
determination. (2) A highly transient concomitant expression is observed in the
caudal intraembryonic definitive endoderm, suggesting that these factors are
involved in the specification of intraembryonic hemopoietic precursors. (3) Lmo2
and GATA-3 are expressed within the hemopoietic clusters located in the aortic
floor during fetal liver colonisation. Furthermore, a strong GATA-3 signal
allowed us to uncover previously unreported mesodermal aggregates beneath the
aorta. A combined in situ and immunocytological analysis strongly suggests that
ventral mesodermal GATA-3 patches are involved in the process of intraembryonic
stem cell generation.

PMID: 10631184 [PubMed - indexed for MEDLINE]


---------------------------------------------------------------