Disease relevance of Hematopoiesis

• Our results showed that GM-CSF is a potent stimulator of hematopoiesis in vivo and may produce hematologic improvement in the short term (8 to 32 weeks of observation) in patients with myelodysplastic syndrome [1].
• The second is deregulated hematopoiesis in both ICSBP-/- and ICSBP+/- mice that manifests as a syndrome similar to human chronic myelogenous leukemia [2].
• Failure of embryonic hematopoiesis and lethal hemorrhages in mouse embryos heterozygous for a knocked-in leukemia gene CBFB-MYH11 [3].
• IRF-2-deficient mice exhibited bone marrow suppression of hematopoiesis and B lymphopoiesis and mortality following lymphocytic choriomeningitis virus infection [4].
• Interleukin-6 (IL-6) is a multifunctional cytokine that regulates various aspects of the immune response, acute-phase reaction and haematopoiesis (for reviews see refs 1, 2) [5].

Psychiatry related information on Hematopoiesis

• Lithium is highly effective in the treatment of bipolar disorder and also has multiple effects on embryonic development, glycogen synthesis, hematopoiesis, and other processes [6].
• Colony-stimulating factor 1 (CSF-1) is a cytokine involved in hematopoiesis and perhaps more importantly in the early stages of immunological defense mechanisms [7].
• The studies showed that the hepatic period of hematopoietic activity was correlated with the critical period of maternal infection, which suggested that B19 might have affinity for erythroid lineage cells at the stage of hematopoiesis [8].

High impact information on Hematopoiesis

• Cdk6-null mice are viable and develop normally although hematopoiesis is slightly impaired [9].
• Ang-1, the ligand for Tie2, enhanced the ability of HSCs to become quiescent and also induced their adhesion to bone, protecting them from stresses that suppress hematopoiesis [10].
• The similar autosomal recessive disease of dogs, canine cyclic hematopoiesis, is not caused by mutations in ELA2 (data not shown) [11].
• Both RUNX1 and CBFbeta are essential for hematopoiesis [12].
• To investigate this issue, we rescued hematopoiesis of Cbfb(-/-) mice by introducing Cbfb using the Gata1 promoter [12].

Chemical compound and disease context of Hematopoiesis

• C-myb is involved in regulating normal human hematopoiesis, and inhibits dimethyl sulfoxide-induced differentiation of Friend murine erythroleukemia (F-MEL) cells [13].
• In vitro studies suggest that all-trans retinoic acid (ATRA) synergizes with erythropoietin (EPO) for the stimulation of hematopoiesis in patients with myelodysplastic syndrome (MDS) [14].
• Effect of human immunodeficiency virus-1 envelope glycoprotein on in vitro hematopoiesis of umbilical cord blood [15].
• The apparent turnover pattern of the dTTP pool of megaloblastic anemia marrow cells, in the presence or absence of hydroxyurea, did not differ significantly from that of normoblastic hematopoiesis [16].
• Stimulation of hematopoiesis by amifostine in patients with myelodysplastic syndrome [17].

Biological context of Hematopoiesis

• The c-kit proto-oncogene product is a major regulator of early hematopoiesis in mice [18].
• Embryos with homozygous mutations in AML1 showed normal morphogenesis and yolk sac-derived erythropoiesis, but lacked fetal liver hematopoiesis and died around E12 [19].
• The rescued Cbfb(-/-) mice recapitulated fetal liver hematopoiesis in erythroid and megakaryocytic lineages and survived until birth, but showed severely delayed bone formation [12].
• AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis [19].
• Mice homozygous for the recessive allelic mutation motheaten (me) or viable motheaten (mev) on chromosome 6 develop severe defects in hematopoiesis [20].

Anatomical context of Hematopoiesis

• Thus, there are lymphocyte-specific, developmentally regulated requirements for alpha4 integrins in hematopoiesis in the bone marrow [21].
• Moreover, this hematopoietic defect was intrinsic to the stem cells in that AML1-/-ES cells failed to contribute to hematopoiesis in chimeric animals [19].
• Mice deficient in Cbfbeta have a severe block in fetal liver hematopoiesis at the stage of hematopoietic stem cell (HSC) emergence [22].
• To investigate the role of HSCs in endothelial cell (EC) development, we analyzed AML1-deficient embryos, which lack definitive hematopoiesis [23].
• We and others previously demonstrated that homozygous disruption of the mouse Cbfa2 (AML1) gene results in embryonic lethality at midgestation due to hemorrhaging in the central nervous system and blocks fetal liver hematopoiesis [24].

Associations of Hematopoiesis with chemical compounds

• The effect of lithium on murine hematopoiesis in a liquid culture system [25].
• The products of androgen metabolism may also play active regulatory roles in hematopoiesis and in the regulation of certain hepatic enzymes [26].
• These studies demonstrate a reproducible way to immortalize lymphohematopoietic progenitors and implicate specific roles for retinoic acid receptors at two distinct stages of hematopoiesis [27].
• We have investigated the function of TIE2/TEK receptor tyrosine kinase in the development of definitive hematopoiesis [28].
• The glycoprotein IIb molecule is expressed on early murine hematopoietic progenitors and regulates their numbers in sites of hematopoiesis [29].

Gene context of Hematopoiesis

• An impairment of primitive hematopoiesis was also observed, however, suggesting a possible additional function of Cbfb-MYH11 [3].
• Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis [30].
• At the earliest stage of vascular development, mice lacking Acvrl1 develop large shunts between arteries and veins, downregulate arterial Efnb2 and fail to confine intravascular haematopoiesis to arteries [31].
• Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development [32].
• Vascular endothelial growth factor (VEGF) is a principal regulator of blood vessel formation and haematopoiesis, but the mechanisms by which VEGF differentially regulates these processes have been elusive [33].

Analytical, diagnostic and therapeutic context of Hematopoiesis

• By gene targeting in mouse embryonic stem cells, we demonstrate that the transcription factor GATA-2 plays a critical role in haematopoiesis, particularly of an adult type [34].
• These results show that (i) c-myb plays a critical role in regulating normal human hematopoiesis and (ii) the combined use of antisense oligodeoxynucleotides and hematopoietic cell culture techniques will provide a powerful tool for studying the role of proteins encoded by proto-oncogenes, or other specific genes, in normal human hematopoiesis [35].
• Previously, we found that Runx1 (AML1), a DNA-binding protein that is homologous to Drosophila Runt and has critical roles in hematopoiesis and leukemogenesis, is poorly expressed in innervated muscle, but strongly induced in muscle shortly after denervation [36].
• This animal model should prove useful for further investigation of the function of IL-6 in normal and abnormal hematopoiesis and in inflammatory responses [37].
• However, in subsequent cycles of chemotherapy, the stimulatory effect of GM-CSF on hematopoiesis was substantially diminished [38].

References