Lhx2 expression in hematopoietic progenitor/stem cells in vivo causes a chronic myeloproliferative disorder and altered globin expression

• Tipo: Artigo em Revista Científica Internacional
• Data: 2003

Autores

Richter, K (Autor) Outra; Perpetua Pinto do O (Autor) Outra; Hagglund, AC (Autor) Outra; Wahlin, A (Autor) Outra; Carlsson, L (Autor) Outra

Revista

Título: Haematologica

Vol. 88

Páginas: 1336-1347

ISSN: 0390-6078

Editora: FERRATA STORTI FOUNDATION

Indexação

ISI Web of Knowledge - 10 Citações

Scopus - 8 Citações

Outras Informações

ID Authenticus: P-008-PCJ

Abstract (EN): Background and Objectives. Chronic myeloproliferative disorders (CMDs) are thought to be due to mutation(s) in a single clone at the level of the hematopoietic stem cell (HSC). Such mutations and additional mutations causing progression of the disease are largely unknown. Chronic myeloid leukemia (CML) is a CMD characterized by a chromosomal translocation between chromosomes 9 and 22 creating the fusion protein BCR-ABL. This translocation has also been suggested to cause mis-expression of the LIM-homeobox gene Lhx2 in hematopoietic cells. We have previously shown that Lhx2 expression in mouse HSC generates cytokine-dependent stem cell-like cell lines that can produce long-term repopulation in stem cell-deficient mice. Design and Methods. Since the consequences of Lhx2 expression in hematopoietic cells in vivo were unknown, mice engrafted with the stem cell-like cell lines were analyzed in detail for any pathologic changes. Results. Expression of Lhx2 was maintained in vivo and most engrafted mice developed a myeloproliferative disorder characterized by splenomegaly, extramedullary hematopoiesis and anemia. The disorder was transplantable and the Lhx2-expressing cells could also cause acute leukemia. The anemia was due to both a reduced number of circulating erythrocytes and a reduced mean corpuscular hemoglobin concentration (MCHC). Interpretation and Conclusions. These observations suggest that constitutive expression of Lhx2 in hematopoietic cells causes CMD, and also that a novel cell-autonomous mechanism can contribute to anemia.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12