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The predicting role of substance P in the neoplastic transformation of the hypoplastic bone marrow.

ABSTRACT: AIMS: To estimate the expression of substance P in the haematopoietic cells of hypoplastic bone marrow and define its relationship with the course of bone marrow hypoplasia. METHODS: Bone marrow specimens were obtained from 42 children with bone marrow hypoplasia who were hospitalised in the Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Poznan, Poland, between 1996 and 2003. Substance P and Ki-67 expression were evaluated using immunochemical and hybridocytochemical assays. RESULTS: The expression of substance P (as evidenced by both immunocytochemical and hybridisation techniques) was confirmed in the cytoplasm of B lymphocytes in 8 of 11 children who developed acute leukaemia in 45 (SD 12) days. The percentage of substance P-positive cells ranged from 67.6 to 95.8 (mean of 81.5% cells with immunocytochemistry and 84.3% with in situ hybridisation). The risk of development of leukaemia secondary to bone marrow hypoplasia was found to be significant (p<0.001) in those children who expressed substance P in normal-looking lymphocytes at the initial bone marrow evaluation. CONCLUSIONS: The presence of substance P in B lymphocytes of hypoplastic bone marrow may predict its neoplastic transformation. A marked correlation between substance P-positive bone marrow pattern and the expansion of tumour cells may prove the potential value of this oligopeptide in the pathogenesis of leukaemia.

SUBMITTER: Nowicki M

PROVIDER: S-EPMC1860490 | biostudies-literature | 2006 Sep

REPOSITORIES: biostudies-literature

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The predicting role of substance P in the neoplastic transformation of the hypoplastic bone marrow.

Nowicki M M Ostalska-Nowicka D D Konwerska A A Miskowiak B B

Journal of clinical pathology 20060901 9

<h4>Aims</h4>To estimate the expression of substance P in the haematopoietic cells of hypoplastic bone marrow and define its relationship with the course of bone marrow hypoplasia.<h4>Methods</h4>Bone marrow specimens were obtained from 42 children with bone marrow hypoplasia who were hospitalised in the Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Poznan, Poland, between 1996 and 2003. Substance P and Ki-67 expression were evaluated us ...[more]

PMID: 16935970

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Project description:Leukemogenic potential of MLL fusion with the coiled-coil domain-containing partner genes and the downstream target genes of this type of MLL fusion have not been clearly investigated. In this study, we demonstrated that the coiled-coil-four-helix bundle structure of EB1 that participated in the MLL/EB1 was required for immortalizing mouse bone marrow (BM) cells and producing myeloid, but not lymphoid, cell lines. Compared to MLL/AF10, MLL/EB1 had low leukemogenic ability. The MLL/EB1 cells grew more slowly owing to increased apoptosis in vitro and induced acute monocytic leukemia with an incomplete penetrance and longer survival in vivo. A comparative analysis of transcriptome profiling between MLL/EB1 and MLL/AF10 cell lines revealed that there was an at least two-fold difference in the induction of 318 genes; overall, 51.3% (163/318) of the genes were known to be bound by MLL, while 15.4% (49/318) were bound by both MLL and MLL/AF9. Analysis of the 318 genes using Gene Ontology-PANTHER overrepresentation test revealed significant differences in several biological processes, including cell differentiation, proliferation/programmed cell death, and cell homing/recruitment. The Ets1 gene, bound by MLL and MLL/AF9, was involved in several biological processes. We demonstrated that Ets1 was selectively upregulated by MLL/EB1. Short hairpin RNA knockdown of Ets1 in MLL/EB1 cells reduced the expression of CD115, apoptosis rate, competitive engraftment to BM and spleen, and incidence of leukemia and prolonged the survival of the diseased mice. Our results demonstrated that MLL/EB1 upregulated Ets1, which controlled the balance of leukemia cells between apoptosis and BM engraftment/clonal expansion. Novelty and impact of this study The leukemogenic potential of MLL fusion with cytoplasmic proteins containing coiled-coil dimerization domains and the downstream target genes of this type of MLL fusion remain largely unknown. Using a retroviral transduction/transplantation mouse model, we demonstrated that MLL fusion with the coiled-coil-four-helix bundle structure of EB1 has low leukemogenic ability; Ets1, which is upregulated by MLL/EB1, plays a critical role in leukemic transformation by balance between apoptosis and BM engraftment/clonal expansion.

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The predicting role of substance P in the neoplastic transformation of the hypoplastic bone marrow.

Publications

The predicting role of substance P in the neoplastic transformation of the hypoplastic bone marrow.

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