Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
Spleens of myelofibrosis patients contain malignant hematopoietic stem cells
Xiaoli Wang, … , Attilio Orazi, Ronald Hoffman
Xiaoli Wang, … , Attilio Orazi, Ronald Hoffman
Published October 1, 2012
Citation Information: J Clin Invest. 2012;122(11):3888-3899. https://doi.org/10.1172/JCI64397.
View: Text | PDF
Research Article Hematology

Spleens of myelofibrosis patients contain malignant hematopoietic stem cells

  • Text
  • PDF
Abstract

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/IL2Rγnull) 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

×

Figure 1

Enhanced human hematopoiesis in NSG mice receiving transplants of splenic MF CD34+ cells.

Options: View larger image (or click on image) Download as PowerPoint
Enhanced human hematopoiesis in NSG mice receiving transplants of spleni...
(A, C, E, and G) The degree of MF hematopoietic cell engraftment is indicated by the percentage of hCD45+ cells detected within the marrow (A), spleen (C), thymus (E), and PB (G) of the NSG mice. (B, D, F, and H) Percentage of hCD34+ cells present within the hCD45+ cell population within the marrow (B), spleen (D), thymus (F), and PB (H) of the NSG mice. The x axis indicates the number of CD34+ cells (×104) injected. All data points represent the mean ± SD from 5–6 different mice, except studies in which 2 × 106 PB MF cells were infused when only 3 animals received transplants due to the limited numbers of CD34+ cells available from the PB of individual patients. P values (Student’s t test) are shown in Supplemental Table 6. Note: ≥0.3% hCD45+ cells were detected in the thymi of mice transplanted with splenic MF CD34+ cells (2 × 105 or 2 × 106) from all 6 patients, while no human cell engraftment was detected in the thymi of mice receiving PB MF CD34+ cells. (I) An increase in splenic weight was observed in mice receiving only splenic MF CD34+ cells. The y axis indicates the fold increase in spleen weight in mice receiving splenic or PB MF CD34+ cells as compared with that of mice receiving PBS alone.
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts