Behavior of CD34+ cells isolated from patients with polycythemia vera in NOD/SCID mice

Takefumi Ishii, Yan Zhao, Selcuk Sozer, Jun Shi, Wei Zhang, Ronald Hoffman, Mingjiang Xu

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Objective: We investigated if polycythemia vera (PV) peripheral blood (PB) CD34+ cells contain cells capable of engrafting nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice and if the JAK2V617F mutational burden of these cells alters their behavior in NOD/SCID mice. Materials and Methods: CD34+ cells isolated from patients with PV, idiopathic myelofibrosis (IM), or granulocyte colony-stimulating factor-mobilized normal donors were transplanted into sublethally irradiated NOD/SCID mice. Cells engrafted into the NOD/SCID mice were analyzed flow cytometrically using lineage-specific antibodies. Genomic DNA was extracted from granulocytes, CD34+ cells, and sorted human CD45+ cells purified from the bone marrow cells of these mice to examine their JAK2V617F mutational burdens. Results: Multilineage human cell engraftment was observed in mice transplanted with CD34+ cells from mobilized normal volunteers, IM patients and PV patients with high JAK2V617F burden, but not in mice receiving grafts from PV patients with low JAK2V617F burden. The differentiation program of engrafting PV CD34+ cells with high JAK2V617F burden was remarkably different than that of IM CD34+ cells. The JAK2V617F allele frequency in the human CD45+ cells isolated from the mice receiving CD34+ cells was lower than that observed in the CD34+ cell grafts, indicating the persistence of a JAK2V617F negative compartment of stem cells. Conclusion: We conclude that PB CD34+ cells from PV patients with high JAK2V617F burden and patients with IM contain NOD/SCID repopulating cells, and that differentiation program of IM and PV CD34+ cells are dramatically different.

Original languageEnglish (US)
Pages (from-to)1633-1640
Number of pages8
JournalExperimental Hematology
Volume35
Issue number11
DOIs
StatePublished - Nov 2007
Externally publishedYes

Fingerprint

Polycythemia Vera
SCID Mice
Primary Myelofibrosis
Blood Cells
Transplants
Granulocyte Colony-Stimulating Factor
Granulocytes
Gene Frequency
Bone Marrow Cells

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Behavior of CD34+ cells isolated from patients with polycythemia vera in NOD/SCID mice. / Ishii, Takefumi; Zhao, Yan; Sozer, Selcuk; Shi, Jun; Zhang, Wei; Hoffman, Ronald; Xu, Mingjiang.

In: Experimental Hematology, Vol. 35, No. 11, 11.2007, p. 1633-1640.

Research output: Contribution to journalArticle

Ishii, Takefumi ; Zhao, Yan ; Sozer, Selcuk ; Shi, Jun ; Zhang, Wei ; Hoffman, Ronald ; Xu, Mingjiang. / Behavior of CD34+ cells isolated from patients with polycythemia vera in NOD/SCID mice. In: Experimental Hematology. 2007 ; Vol. 35, No. 11. pp. 1633-1640.
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AU - Sozer, Selcuk

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AU - Zhang, Wei

AU - Hoffman, Ronald

AU - Xu, Mingjiang

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