Bone marrow stroma in childhood myelodysplastic syndrome: composition, ability to sustain hematopoiesis in vitro, and altered gene expression

Borojević, Radovan; Roela, Rosimeire Aparecida; Rodarte, Renato Santos; Thiago, Leandro S.; Pasini, Fátima Solange; Conti, F; Rossi, Maria Isabel D.; Reis, Luiz F. L.; Lopes, Luiz Fernando; Brentani, Maria Mitzi

doi:10.1016/j.leukres.2003.11.019

Cited by 38 publications

(26 citation statements)

References 35 publications

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“…18 It has been speculated that microenvironmental changes are involved in the pathogenesis of MDS. [28][29][30] However, since there was no significant difference in the engraftment of MDS-originated cells between normal (allogeneic-) and patient-derived (autologous-) MSC transplanted groups tested in this study, humanization of the microenvironment appeared more important, at least in our present study. One interesting finding in the serial transplantation study was that AML-MRC cells that had already engrafted in mice no longer required auxiliary cells or an intramedullary route of administration in subsequent transplants, perhaps because the cells with an ability to overcome hurdles to homing and engraftment in a murine host were selected during the serial transplants.…”

Section: Discussionmentioning

confidence: 46%

Establishment of a xenograft model of human myelodysplastic syndromes

Muguruma¹,

Matsushita²,

Yahata³

et al. 2010

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundTo understand how myelodysplastic syndrome cells evolve from normal stem cells and gain competitive advantages over normal hematopoiesis, we established a murine xenograft model harboring bone marrow cells from patients with myelodysplastic syndromes or acute myeloid leukemia with myelodysplasia-related changes. Design and Methods Bone marrow CD34+ cells obtained from patients were injected, with or without human mesenchymal stem cells, into the bone marrow of non-obese diabetic/severe combined immunodeficient/IL2Rγ null hosts. Engraftment and differentiation of cells derived from the patients were investigated by flow cytometry and immunohistochemical analysis. ResultsCo-injection of patients' cells and human mesenchymal stem cells led to successful engraftment of patient-derived cells that maintained the immunophenotypes and genomic abnormalities of the original patients. Myelodysplastic syndrome-originated clones differentiated into mature neutrophils, megakaryocytes, and erythroblasts. Two of the samples derived from patients with acute myeloid leukemia with myelodysplasia-related changes were able to sustain neoplastic growth into the next generation while these cells had limited differentiation ability in the murine host. The hematopoiesis of mice engrafted with patients' cells was significantly suppressed even when human cells accounted for less than 1% of total marrow mononuclear cells. Histological studies revealed invasion of the endosteal surface by patient-derived CD34 + cells and disruption of extracellular matrix architecture, which probably caused inhibition of murine hematopoiesis. ConclusionsWe established murine models of human myelodysplastic syndromes using cells obtained from patients: the presence of neoplastic cells was associated with the suppression of normal host hematopoiesis. The efficiency of engraftment was related to the presence of an abnormality in chromosome 7.Key words: xenograft, MDS, NOG mouse, niche, MSC. syndromes. Haematologica 2011;96(4):543-551. doi:10.3324/haematol.2010 This is an open-access paper. Citation: Muguruma Y, Matsushita H, Yahata T, Yumino S, Tanaka Y, Miyachi H, Ogawa Y, Kawada H, Ito M, and Ando K. Establishment of a xenograft model of human myelodysplastic Establishment of a xenograft model of human myelodysplastic syndromes

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Section: Discussionmentioning

confidence: 46%

Establishment of a xenograft model of human myelodysplastic syndromes

Muguruma¹,

Matsushita²,

Yahata³

et al. 2010

Haematologica

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show abstract

“…An unfavorable alteration of the marrow microenvironment, as observed by in vitro evaluations, 37,38 appears to be a more plausible explanation.…”

Section: Discussionmentioning

confidence: 83%

Marrow fibrosis predicts early fatal marrow failure in patients with myelodysplastic syndromes

et al. 2007

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“…Several studies have proposed that important quantitative and functional alterations occur in the MSCs of patients with different hematologic disorders. 16,17 MSCs seem to have a relevant role in AML because they prevent spontaneous and induced apoptosis and may attenuate chemotherapy-induced cell death. This possibility has been confirmed by the finding that cocultivation of a leukemic cell line with the murine stroma cell line MS-5 can block apoptosis.…”

Section: Introductionmentioning

confidence: 99%