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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1699-1705.
Prepublished online as a Blood First Edition Paper on October 7, 2004; DOI 10.1182/blood-2004-06-2485.
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NEOPLASIA
The constitutive mobilization of bone marrow-repopulating cells into the peripheral blood in idiopathic myelofibrosis
Mingjiang Xu,
Edward Bruno,
Joseph Chao,
Hongyu Ni,
Valerie Lindgren,
Rafael Nunez,
Nadim Mahmud,
Guido Finazzi,
Steven M. Fruchtman,
Uday Popat,
Enli Liu,
Josef T. Prchal,
Damiano Rondelli,
Giovanni Barosi, and
Ronald Hoffman
From the Section of Hematology/Oncology and the Department of Pathology, University of Illinois at Chicago Cancer Center, University of Illinois College of Medicine, Chicago, IL; the Department of Hematology, Ospedali Riuniti, Bergamo, Italy; Mount Sinai School of Medicine, New York, NY; Baylor College of Medicine, Houston, TX; Instituto di Ricovere Cura a Corattere Scientifico (IRCCS) Policlinico S Matteo, Pavia, Italy; and The MPD Research Consortium, Chicago, IL.
Idiopathic myelofibrosis (IM) is characterized by the constitutive mobilization of CD34+ cells. IM peripheral blood (PB) CD34+ cells had a reduced cloning efficiency and a lower frequency of cobblestone areas compared with normal granulocyte colony-stimulating factor (G-CSF)-mobilized PB CD34+ cells. IM CD34+ cells engrafted nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice, demonstrating that they contain bone marrow (BM)-repopulating cells. G-CSF-mobilized CD34+ cells produced multiple hematopoietic lineages within the NOD/SCID mice with a predominance of CD19+ cells. By contrast, IM CD34+ cells produced predominantly CD33+ cells, increased numbers of CD41+ cells, but fewer CD19+ cells. Transcriptional clonality assays of the engrafted human IM cells demonstrated their clonal origin. CD34+ cells from one patient isolated prior to leukemic transformation were capable of generating acute leukemia in NOD/SCID mice. The engrafted human cells exhibited the same abnormal karyotype as primary cells in a portion of the population. These findings demonstrate that BM-repopulating cells and more differentiated progenitor cells are constitutively mobilized into the PB in IM, and that their differentiation program is abnormal. In addition, the NOD/SCID model may be useful in gaining an understanding of the events occurring during the transition of IM to acute leukemia. (Blood. 2005;105:1699-1705)
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