1: Blood. 2005 Sep 15;106(6):2147-55. Epub 2005 May 24. 

Dysplastic definitive hematopoiesis in AML1/EVI1 knock-in embryos.

Maki K, Yamagata T, Asai T, Yamazaki I, Oda H, Hirai H, Mitani K.

Department of Hematology, Dokkyo University School of Medicine, 880
Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi 321-0293, Japan.

The AML1/EVI1 chimeric gene is created by the t(3;21)(q26;q22) chromosomal
translocation seen in patients with leukemic transformation of myelodysplastic
syndrome or blastic crisis of chronic myelogenous leukemia. We knocked-in the
AML1/EVI1 chimeric gene into mouse Aml1 genomic locus to explore its effect in
developmental hematopoiesis in vivo. AML1/EVI1/+ embryo showed defective
hematopoiesis in the fetal liver and died around embryonic day 13.5 (E13.5) as a
result of hemorrhage in the central nervous system. The peripheral blood had
yolk-sac-derived nucleated erythroblasts but lacked erythrocytes of the
definitive origin. Although E12.5 fetal liver contained progenitors for
macrophage only, E13.5 fetal liver contained multilineage progenitors capable of
differentiating into dysplastic myelocyte and megakaryocyte. No erythroid
progenitor was detected in E12.5 or E13.5 fetal liver. Hematopoietic progenitors
from E13.5 AML1/EVI1/+ fetal liver were highly capable of self-renewal compared
with those from wild-type liver. Maintained expression of PU.1 gene and
decreased expression of LMO2 and SCL genes may explain the aberrant
hematopoiesis in AML1/EVI1/+ fetal liver.

PMID: 15914564 [PubMed - indexed for MEDLINE]


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2: Br J Haematol. 2004 Jul;126(1):3-10. 

Leukaemia -- a developmental perspective.

Izraeli S.

Department of Paediatric Haemato-Oncology, Sackler Faculty of Medicine, Cancer
Research Centre, Safra's Children's Hospital, Sheba Medical Centre, Tel-Aviv
University, Tel-Hashomer, Ramat-Gan, Israel. izraelis@netvision.net.il

Leukaemia is characterized by the accumulation of malignant haematopoietic
precursors. Recent studies have revealed that acquired alterations in genes that
regulate normal haematopoiesis are frequently detected in leukaemia. The
progression to leukaemia depends on additional mutations that promote the
survival of developmentally arrested cells. This review describes three examples
of this general paradigm of leukaemogenesis: RUNX1 abnormalities in acute
leukaemias, GATA1 mutations in the leukaemias of Down syndrome, and SCL and LMO2
ectopic expression in T cell acute lymphoblastic leukaemia.

Publication Types:
    Review

PMID: 15198727 [PubMed - indexed for MEDLINE]


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