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

• Type: Article in International Scientific Journal
• Date: 2003

Authors

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

Journal

Title: Haematologica

Vol. 88

Pages: 1336-1347

ISSN: 0390-6078

Publisher: FERRATA STORTI FOUNDATION

Indexing

ISI Web of Knowledge - 10 Citations

Scopus - 8 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12