scholarly journals Simian immunodeficiency virus inhibits bone marrow hematopoietic progenitor cell growth.

1990 ◽  
Vol 64 (2) ◽  
pp. 656-663 ◽  
Author(s):  
M Watanabe ◽  
D J Ringler ◽  
M Nakamura ◽  
P A DeLong ◽  
N L Letvin
Blood ◽  
1992 ◽  
Vol 80 (6) ◽  
pp. 1443-1447
Author(s):  
WJ Murphy ◽  
G Tsarfaty ◽  
DL Longo

Recombinant human growth hormone (rhGH) was administered to mice to determine its effect on hematopoiesis. BALB/c mice and mice with severe combined immune deficiency (SCID), which lack T cells and B cells, were administered intraperitoneal injections of rhGH for 7 days. Upon analysis, both strains of mice exhibited an increase in splenic and bone marrow hematopoietic progenitor cell content and cellularity, indicating that rhGH can act as a hematopoietic growth factor. C57BL/6 mice were then placed on azidothymidine (AZT). AZT is a reverse transcriptase inhibitor currently used as a treatment for acquired immune deficiency syndrome (AIDS), but which also produces significant myelotoxic effects. Treatment of mice with rhGH partially counteracted the myelosuppressive properties of AZT. Bone marrow cellularity, hematocrit values, white blood cell counts, and splenic hematopoietic progenitor cell content were all significantly increased if rhGH (20 micrograms injected intraperitoneally every other day) was concurrently administered with AZT. Administration of ovine GH (ovGH), which, unlike rhGH, has no effect on murine prolactin receptors, also prevented the erythroid-suppressive effects of AZT in mice, but had no significant effect on granulocyte counts. Thus, the effects of GH are mediated at least in part through GH receptors in vivo. Additionally, when mice were initially myelosuppressed by several weeks of AZT treatment, the subsequent administration of ovGH resulted in an increase in splenic hematopoietic progenitor cells. No significant pathologic effects were observed in mice receiving either repeated rhGH or ovGH injections. Thus, GH exerts significant direct hematopoietic growth-promoting effects in vivo and may be of potential clinical use to promote hematopoiesis in the face of myelotoxic therapy.


Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3296-3303 ◽  
Author(s):  
Kai-Ling Fu ◽  
Jerome R. Lo Ten Foe ◽  
Hans Joenje ◽  
Kathleen W. Rao ◽  
Johnson M. Liu ◽  
...  

Abstract Fanconi anemia (FA) is an autosomal recessive genetic disorder characterized by a variety of physical anomalies, bone marrow failure, and an increased risk for malignancy. FA cells exhibit chromosomal instability and are hypersensitive to DNA cross-linking agents such as mitomycin C (MMC). FA is a clinically heterogeneous disorder and can be functionally divided into at least five different complementation groups (A-E). We previously described the use of a retroviral vector expressing the FAC cDNA in the complementation of mutant hematopoietic cells from FA-C patients. This vector is currently being tested in a clinical trial of ex vivo hematopoietic progenitor cell transduction. The FA-A group accounts for over 65% of all FA cases, and the FAA cDNA was recently identified by both expression and positional cloning techniques. We report here the transduction and phenotypic correction of lymphoblastoid cell lines from four unrelated FA-A patients, using two amphotropic FAA retroviral vectors. Expression of the FAA transgene was adequate to normalize cell growth, cell-cycle kinetics, and chromosomal breakage in the presence of MMC. We then analyzed the effect of retroviral vector transduction on hematopoietic progenitor cell growth. After FAA transduction of mutant progenitor cells, either colony number or colony size increased in the presence of MMC. In addition, FAA but not FAC retroviral transduction markedly improved colony growth of progenitor cells derived from an unclassified FA patient. FAA retroviral vectors should be useful for both complementation studies and clinical trials of gene transduction.


2000 ◽  
Vol 18 (5) ◽  
pp. 947-947 ◽  
Author(s):  
Ivana N. M. Micallef ◽  
Debra M. Lillington ◽  
John Apostolidis ◽  
John A. L. Amess ◽  
Michael Neat ◽  
...  

PURPOSE: To evaluate the incidence of and risk factors for therapy-related myelodysplasia (tMDS) and secondary acute myelogenous leukemia (sAML), after high-dose therapy (HDT) with autologous bone marrow or peripheral-blood progenitor-cell support, in patients with non-Hodgkin’s lymphoma (NHL). PATIENTS AND METHODS: Between January 1985 and November 1996, 230 patients underwent HDT comprising cyclophosphamide therapy and total-body irradiation, with autologous hematopoietic progenitor-cell support, as consolidation of remission. With a median follow-up of 6 years, 27 (12%) developed tMDS or sAML. RESULTS: Median time to development of tMDS or sAML was 4.4 years (range, 11 months to 8.8 years) after HDT. Karyotyping (performed in 24 cases) at diagnosis of tMDS or sAML revealed complex karyotypes in 18 patients. Seventeen patients had monosomy 5/5q−, 15 had −7/7q−, seven had −18/18q−, seven had −13/13q−, and four had −20/20q−. Twenty-one patients died from complications of tMDS or sAML or treatment for tMDS or sAML, at a median of 10 months (range, 0 to 26 months). Sixteen died without evidence of recurrent lymphoma. Six patients were alive at a median follow-up of 6 months (range, 2 to 22 months) after diagnosis of tMDS or sAML. On multivariate analysis, prior fludarabine therapy (P = .009) and older age (P = .02) were associated with the development of tMDS or sAML. Increased interval from diagnosis to HDT and bone marrow involvement at diagnosis were of borderline significance (P = .05 and .07, respectively). CONCLUSION: tMDS and sAML are serious complications of HDT for NHL and are associated with very poor prognosis. Alternative strategies for reducing their incidence and for treatment are needed.


2014 ◽  
Vol 181 (1) ◽  
pp. 76 ◽  
Author(s):  
Hebist Berhane ◽  
Michael W. Epperly ◽  
Julie Goff ◽  
Ronny Kalash ◽  
Shaonan Cao ◽  
...  

2016 ◽  
Vol 62 (suppl 1) ◽  
pp. 10-15 ◽  
Author(s):  
Fernando Barroso Duarte ◽  
Benedito de Pina Almeida Prado ◽  
Garles Miller Matias Vieira ◽  
Luciano J. Costa

SUMMARY Selected patients with certain hematological malignancies and solid tumors have the potential to achieve long-term survival with autologous hematopoietic progenitor cell transplant. The collection of these cells in peripheral blood avoids multiple bone marrow aspirations, results in faster engraftment and allows treatment of patients with infection, fibrosis, or bone marrow hypocellularity. However, for the procedure to be successful, it is essential to mobilize a sufficient number of progenitor cells from the bone marrow into the blood circulation. Therefore, a group of Brazilian experts met in order to develop recommendations for mobilization strategies adapted to the reality of the Brazilian national health system, which could help minimize the risk of failure, reduce toxicity and improve the allocation of financial resources.


Science ◽  
2008 ◽  
Vol 322 (5909) ◽  
pp. 1861-1865 ◽  
Author(s):  
Angela Colmone ◽  
Maria Amorim ◽  
Andrea L. Pontier ◽  
Sheng Wang ◽  
Elizabeth Jablonski ◽  
...  

The host tissue microenvironment influences malignant cell proliferation and metastasis, but little is known about how tumor-induced changes in the microenvironment affect benign cellular ecosystems. Applying dynamic in vivo imaging to a mouse model, we show that leukemic cell growth disrupts normal hematopoietic progenitor cell (HPC) bone marrow niches and creates abnormal microenvironments that sequester transplanted human CD34+(HPC-enriched) cells. CD34+cells in leukemic mice declined in number over time and failed to mobilize into the peripheral circulation in response to cytokine stimulation. Neutralization of stem cell factor (SCF) secreted by leukemic cells inhibited CD34+cell migration into malignant niches, normalized CD34+cell numbers, and restored CD34+cell mobilization in leukemic mice. These data suggest that the tumor microenvironment causes HPC dysfunction by usurping normal HPC niches and that therapeutic inhibition of HPC interaction with tumor niches may help maintain normal progenitor cell function in the setting of malignancy.


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