Document Detail


Spleens of myelofibrosis patients contain malignant hematopoietic stem cells.
MedLine Citation:
PMID:  23023702     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cancer stem cell behavior is thought to be largely determined by intrinsic properties and by regulatory signals provided by the microenvironment. Myelofibrosis (MF) is characterized by hematopoiesis occurring not only in the marrow but also in extramedullary sites such as the spleen. In order to study the effects of these different microenvironments on primitive malignant hematopoietic cells, we phenotypically and functionally characterized splenic and peripheral blood (PB) MF CD34+ cells from patients with MF. MF spleens contained greater numbers of malignant primitive HPCs than PB. Transplantation of PB MF CD34+ cells into immunodeficient (NOD/SCID/IL2Rγ(null)) mice resulted in a limited degree of donor cell chimerism and a differentiation program skewed toward myeloid lineages. By contrast, transplanted splenic MF CD34+ cells achieved a higher level of chimerism and generated both myeloid and lymphoid cells that contained molecular or cytogenetic abnormalities indicating their malignant nature. Only splenic MF CD34+ cells were able to sustain hematopoiesis for prolonged periods (9 months) and were able to engraft secondary recipients. These data document the existence of MF stem cells (MF-SCs) that reside in the spleens of MF patients and demonstrate that these MF-SCs retain a differentiation program identical to that of normal hematopoietic stem cells.
Authors:
Xiaoli Wang; Sonam Prakash; Min Lu; Joseph Tripodi; Fei Ye; Vesna Najfeld; Yan Li; Myron Schwartz; Rona Weinberg; Paul Roda; Attilio Orazi; Ronald Hoffman
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  122     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-12-26     Completed Date:  2013-01-15     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3888-99     Citation Subset:  AIM; IM    
Affiliation:
Division of Hematology/Oncology, Pathology and Surgery, Tisch Cancer Institute, Myeloproliferative Disorders Research Consortium, Mount Sinai School of Medicine, New York, New York 10029, USA.
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MeSH Terms
Descriptor/Qualifier:
Aged
Animals
Antigens, CD34
Female
Hematopoiesis, Extramedullary*
Hematopoietic Stem Cells / metabolism*,  pathology
Humans
Male
Mice
Mice, Inbred NOD
Mice, SCID
Middle Aged
Neoplastic Stem Cells / metabolism*,  pathology
Peripheral Blood Stem Cell Transplantation
Primary Myelofibrosis / metabolism*,  pathology
Spleen / metabolism*,  pathology
Transplantation, Heterologous
Grant Support
ID/Acronym/Agency:
1P01CA108671/CA/NCI NIH HHS; P01 CA108671/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD34
Comments/Corrections

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