Management of anaemia in prostate cancer.

Cancer Invest. 2010 Mar;28(3):280-8

Authors: Colloca G, Venturino A, Vitucci P, Gianni W

Anaemia is a frequent complication of prostate cancer and of its treatments. In Europe prostate cancer accounts for the 10.8% of all malignant neoplasms. Iatrogenic hypogonadism and age-related physiologic changes along with nutritional deficits contribute to increase prevalence of prostate cancer related anaemia. The reason of the present review is to provide clinicians with all aspects of a frequent and multifactorial co-morbidity, whose effects are often underestimated. Erythropoiesis pathology and causes of anaemia in prostate cancer are reviewed. Critical issues of clinical management of anaemia in prostate cancer are discussed.

PMID: 19863346 [PubMed - indexed for MEDLINE]

Use of Human Embryonic Stem Cells to Understand Hematopoiesis and Hematopoietic Stem Cell Niche.

Curr Stem Cell Res Ther. 2010 Mar 8;

Authors: Islam MS, Ni Z, Kaufman DS

Intensive research of hematopoiesis using human embryonic stem cells (hESC) as a unique starting cell population has enabled differentiation and isolation of diverse hematopoietic cell lineages. However, there has been only limited success in derivation of hematopoietic stem cells (HSCs) capable of long-term, multi-lineage engraftment when transplanted into xenogeneic models. Better understanding of the HSC developmental niche, the home for hematopoietic stem and progenitor cells, will aid to advance strategies to derive and assay putative HSCs from hESCs. This review discusses recent status of hematopoietic development from the hESCs and highlights the possibility of developing HSC niche using hESC-derived niche components.

PMID: 20214557 [PubMed - as supplied by publisher]

Wnt and Notch signaling pathways selectively regulating hematopoiesis.

Ann Hematol. 2010 Mar 10;

Authors: Zhou K, Huang L, Zhou Z, Hu C, Liu W, Zhou J, Sun H

Hematopoietic stem and progenitor cells (HSPCs) are the source of all blood cells in the adult body. The pool of HSPCs is formed during embryogenesis process through a well-characterized succession of intra-embryonic regions and organs. The spatial and temporal restrictions in definitive hematopoietic development and the signaling molecules involved are of great interest as these may prove useful for generating and expanding these clinically important cell populations ex vivo. To elucidate the mechanism by which definitive HSPCs expand during this limited developmental time frame, we analyzed the spatial and temporal programmed gene expression patterns of Wnt and Notch signaling members during hematopoietic development. Genes related to the Wnt signaling pathway were up-regulated in E10.5 aorta-gonad-mesonephros (AGM) and E14.5 fetal liver corresponding to the inherent proliferation potential of hematopoietic progenitors, whereas genes related to the Notch signaling pathway were identified as up-regulated in E10.5 AGM, and bone marrow coincides with the maintenance of undifferentiation state of hematopoietic progenitors. Our findings suggest that Wnt and Notch signalings are integrated and are selectively regulating hematopoiesis. The spatial and temporal balance between Wnt and Notch signaling orchestrates the precise progression of hematopoietic progenitors.

PMID: 20217087 [PubMed - as supplied by publisher]

Ontogeny of angiopoietin-like protein 1, 2, 3, 4, 5, and 7 genes during chick embryonic development.

Dev Growth Differ. 2009 Dec;51(9):821-32

Authors: Niki D, Katsu K, Yokouchi Y

Angiopoietin-like proteins (ANGPTLs) are secreted proteins possessing an amino-terminal coiled-coil domain and a carboxyl-terminal fibrinogen-like domain and are known as angiogenic factors. Several members of ANGPTLs also regulate lipid metabolism independently of angiogenic effects, but most of their functions during vertebrate development are not demonstrated. To ascertain their developmental functions, we examined the expression patterns of Angptl1, 2, 3, 4, 5, and 7 orthologues during chick development using whole-mount in situ hybridization. Angptl1 was first detected at embryonic day 3 (E3) in the somite. At E4, Angptl1 was expressed in somite-derivatives and limb mesenchyme. Angptl2 was first detected at E3 in the hindbrain. At E4, Angptl2 was expressed in neuroepithelium of forebrain and hindbrain and partly in the heart. Angptl3 was first detected at E3 and continued to be expressed in the liver and yolk sac at E4. Angptl4 was first detected at E3 in the somites and liver. At E4, Angptl4 was also observed in the heart. Angptl5 was not detected in these developmental stages. Angptl7 was first detected at E3 in the ectoderm overlying the lenses of the eyes. At E4, Angptl7 was specifically expressed in cornea. These data suggest that each member of the ANGPTL family could be related to angiogenesis during various organogeneses of the developing chick embryo.

PMID: 19951324 [PubMed - indexed for MEDLINE]

In vitro human bone marrow analog: clinical potential.

Regen Med. 2010 Mar;5(2):289-98

Authors: Nichols JE, Niles J, Walls S, Cortiella J

Bone marrow is the primary site of hematopoiesis in adult humans. Bone marrow can be cultured in vitro but few simple culture systems fully support hematopoiesis beyond a few months. Human bone marrow analogs are long-term in vitro cultures of marrow stromal and hematopoietic stem cells that can be used to produce cells and products normally harvested from human donors. Bone marrow analog systems should exhibit confluence of the stromal cell populations, persistence of hematopoietic progenitor cells, presence of active regions of hematopoiesis and capacity to produce mature cell types for extended periods of time. Although we are still years away from realizing clinical application of products formed by artificial bone marrow analogs, the process of transitioning this research tool from bench to bedside should be fairly straightforward. The most obvious application of artificial marrow would be for production of autologous hematopoietic CD34(+) stem cells as a stem cell therapy for individuals experiencing bone marrow failure due to disease or injury. Another logical application is for 'blood farming', a process for large-scale in vitro production of red blood cells, white blood cells or platelets, for transfusion or treatment. Other possibilities include production of nonhematopoietic stem cells such as osteogenic stromal cells, osteoblasts and rare pluripotent stem cells. Bone marrow analogs also have great potential as ex vivo human test systems and could play a critical role in drug discovery, drug development and toxicity testing in the future.

PMID: 20210588 [PubMed - in process]

Portal venous endothelium in developing human liver contains haematopoietic and epithelial progenitor cells.

Exp Cell Res. 2010 Mar 5;

Authors: Terrace JD, Hay DC, Samuel K, Anderson RA, Currie IS, Parks RW, Forbes SJ, Ross JA

Future treatments for chronic liver disease are likely to involve manipulation of liver progenitor cells (LPCs). In the human, data characterising the regenerative response is limited and the origin of adult LPCs is unknown. However, these remain critical factors in the design of cell-based liver therapies. The developing human liver provides an ideal model to study cell lineage derivation from progenitors and to understand how foetal haematopoiesis and liver development might explain the nature of the adult LPC population. In 1st trimester human liver, portal venous endothelium (PVE) expressed adult LPC markers and markers of haematopoietic progenitor cells (HPCs) shared with haemogenic endothelium found in the embryonic dorsal aorta. Sorted PVE cells were able to generate hepatoblast-like cells co-expressing CK18 and CK19 in addition to Dlk/pref-1, E-cadherin, albumin and fibrinogen in vitro. Furthermore, PVE cells could initiate haematopoiesis. These data suggest that PVE shares phenotypical and functional similarities both with adult LPCs and embryonic haemogenic endothelium. This indicates that a temporal relationship might exist between progenitor cells in foetal liver development and adult liver regeneration, which may involve progeny of PVE.

PMID: 20211168 [PubMed - as supplied by publisher]

Oncolytic viral purging of leukemic hematopoietic stem and progenitor cells with Myxoma virus.

Cytokine Growth Factor Rev. 2010 Mar 6;

Authors: Rahman MM, Madlambayan GJ, Cogle CR, McFadden G

High-dose chemotherapy and radiation followed by autologous blood and marrow transplantation (ABMT) has been used for the treatment of certain cancers that are refractory to standard therapeutic regimes. However, a major challenge with ABMT for patients with hematologic malignancies is disease relapse, mainly due to either contamination with cancerous hematopoietic stem and progenitor cells (HSPCs) within the autograft or the persistence of residual therapy-resistant disease niches within the patient. Oncolytic viruses represent a promising therapeutic approach to prevent cancer relapse by eliminating tumor-initiating cells that contaminate the autograft. Here we summarize an ex vivo "purging" strategy with oncolytic Myxoma virus (MYXV) to remove cancer-initiating cells from patient autografts prior to transplantation. MYXV, a novel oncolytic poxvirus with potent anti-cancer properties in a variety of in vivo tumor models, can specifically eliminate cancerous stem and progenitor cells from samples obtained from acute myelogenous leukemia (AML) patients, while sparing normal CD34+ hematopoietic stem and progenitor cells capable of rescuing hematopoiesis following high dose conditioning. We propose that a broader subset of patients with intractable hematologic malignancies who have failed standard therapy could become eligible for ABMT when the treatment schema is coupled with ex vivo oncolytic therapy.

PMID: 20211576 [PubMed - as supplied by publisher]

microRNA-29a induces aberrant self-renewal capacity in hematopoietic progenitors, biased myeloid development, and acute myeloid leukemia.

J Exp Med. 2010 Mar 8;

Authors: Han YC, Park CY, Bhagat G, Zhang J, Wang Y, Fan JB, Liu M, Zou Y, Weissman IL, Gu H

The function of microRNAs (miRNAs) in hematopoietic stem cells (HSCs), committed progenitors, and leukemia stem cells (LSCs) is poorly understood. We show that miR-29a is highly expressed in HSC and down-regulated in hematopoietic progenitors. Ectopic expression of miR-29a in mouse HSC/progenitors results in acquisition of self-renewal capacity by myeloid progenitors, biased myeloid differentiation, and the development of a myeloproliferative disorder that progresses to acute myeloid leukemia (AML). miR-29a promotes progenitor proliferation by expediting G1 to S/G2 cell cycle transitions. miR-29a is overexpressed in human AML and, like human LSC, miR-29a-expressing myeloid progenitors serially transplant AML. Our data indicate that miR-29a regulates early hematopoiesis and suggest that miR-29a initiates AML by converting myeloid progenitors into self-renewing LSC.

PMID: 20212066 [PubMed - as supplied by publisher]

Runx1 Isoforms Show Differential Expression Patterns During Hematopoietic Development But Have Similar Functional Effects in Adult Hematopoietic Stem Cells.

Exp Hematol. 2010 Mar 2;

Authors: Challen GA, Goodell MA

OBJECTIVE: RUNX1/AML1 is an essential regulator of hematopoiesis and has multiple isoforms arising from differential splicing and utilization of two promoters. We hypothesized that the rare Runx1c isoform has a distinct role in hematopoietic stem cells (HSCs). METHODS: We have characterized the expression pattern of Runx1c in mouse embryos and human embryonic stem cell (hESC)-derived embryoid bodies using in situ hybridization, and expression levels in mouse and human HSCs by real-time PCR. We then determined the functional effects of Runx1c using enforced retroviral over-expression in mouse HSCs. RESULTS: We observed differential expression profiles of RUNX1 isoforms during hematopoietic differentiation of hESCs. The RUNX1a and RUNX1b isoforms were expressed consistently throughout hematopoietic differentiation whereas the RUNX1c isoform was only expressed at the time of emergence of definitive HSCs. RUNX1c was also expressed in the AGM region of E10.5-11.5 mouse embryos, the region where definitive HSCs arise. These observations suggested that the RUNX1c isoform may be important for the specification or function of definitive HSCs. However, using retroviral over-expression to study the effect of RUNX1 isoforms on HSCs in a gain-of-function system, no discernable functional difference could be identified between RUNX1 isoforms in mouse HSCs. Over-expression of both RUNX1b and RUNX1c induced quiescence in mouse HSCs in vitro and in vivo. CONCLUSIONS: Although the divergent expression profiles of Runx1 isoforms during development suggest specific roles for these proteins at different stages of HSC maturation, we could not detect an important functional distinction in adult mouse HSCs using our assay systems.

PMID: 20206228 [PubMed - as supplied by publisher]

Expression profile of WNT, FZD and sFRP genes in human hematopoietic cells.

Leuk Res. 2010 Mar 4;

Authors: Sercan Z, Pehlivan M, Sercan HO

Identifying gene expression differences in the Wnt signaling pathway specific to leukemic cells can be hampered by the lack of verified knowledge on the expression of WNT genes in normal blood cells. In this study we aimed to determine the expression profile of human WNT, FZD and sFRP genes in normal adult bone marrow, T and B cells; along with the hematopoietic cell lines K562, HL60, Jurkat and Namalwa. Bone marrow and peripheral blood from 16 donors were evaluated and our results were compared with the GeneNote database expression arrays. In bone marrow, only WNT3, WNT10A, FZD3, FZD7 and sFRP1 genes are constitutively expressed. Lymphocytes express WNT7A, WNT9B, FZD6 and FZD7 in addition to the genes above, but T cells differ in that they lose sFRP1 expression and gain constitutive expression of WNT16. An established "normal" profile of the Wnt genes in various blood cells will provide a fundamental basis for research investigating hematopoiesis and cellular processes during leukemic transformation.

PMID: 20206998 [PubMed - as supplied by publisher]