Correction of the abnormal trafficking of primary myelofibrosis CD34 + cells by treatment with chromatin-modifying agents

Wang Xiaoli, Zhang Wei, Ishii Takefumi, Selcuk Sozer, Wang Jiapeng, Xu Mingjiang, Ronald Hoffman

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The abnormal trafficking of CD34+ cells is a unique characteristic of primary myelofibrosis (PMF). We have further studied the behavior of PMF CD34+ cells by examining their homing to the marrow and the spleens of nonobese diabetic/severe combined immunodeficient (NOD/SCID)mice. Following the infusion of PMF and normal granulocyte colony-stimulating factor-mobilized peripheral blood (mPB)CD34+ cells into NOD/SCID mice, reduced numbers of PMF CD34+ cells and granulocyte-macrophage colony-forming unit (CFU-GM) compared with mPB were detected in the marrow of these mice, whereas similar numbers of PMF and mPB CD34+ cells and CFU-GM homed to their spleens. The abnormal homing of PMF CD34+ cells was associated with reduced expression of CXCR4, but was not related to the presence of JAK2V617F. The sequential treatment of PMF CD34+ cells with the chromatin-modifying agents 5-aza-2′- deoxycytidine (5azaD) and trichostatin A (TSA), but not treatment with small molecule inhibitors of JAK2, resulted in the generation of increased numbers of CD34+CXCR4+ cells, which was accompanied by enhanced homing of PMF CD34+ cells to the marrow but not the spleens of NOD/SCID mice. Following 5azaD/TSA treatment, JAK2V617F-negative PMF hematopoietic progenitor cells preferentially homed to the marrow but not the spleens of recipient mice. Our data suggest that PMF CD34+ cells are characterized by a reduced ability to home to the marrow but not the spleens of NOD/SCID mice and that this homing defect can be corrected by sequential treatment with chromatin-modifying agents.

Original languageEnglish (US)
Pages (from-to)7612-7618
Number of pages7
JournalCancer Research
Volume69
Issue number19
DOIs
StatePublished - Oct 1 2009
Externally publishedYes

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Primary Myelofibrosis
Chromatin
SCID Mice
decitabine
Spleen
Bone Marrow
Granulocyte-Macrophage Progenitor Cells
trichostatin A
Blood Cells
Aptitude
Granulocyte Colony-Stimulating Factor
Hematopoietic Stem Cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Correction of the abnormal trafficking of primary myelofibrosis CD34 + cells by treatment with chromatin-modifying agents. / Xiaoli, Wang; Wei, Zhang; Takefumi, Ishii; Sozer, Selcuk; Jiapeng, Wang; Mingjiang, Xu; Hoffman, Ronald.

In: Cancer Research, Vol. 69, No. 19, 01.10.2009, p. 7612-7618.

Research output: Contribution to journalArticle

Xiaoli, W, Wei, Z, Takefumi, I, Sozer, S, Jiapeng, W, Mingjiang, X & Hoffman, R 2009, 'Correction of the abnormal trafficking of primary myelofibrosis CD34 + cells by treatment with chromatin-modifying agents', Cancer Research, vol. 69, no. 19, pp. 7612-7618. https://doi.org/10.1158/0008-5472.CAN-09-1823
Xiaoli, Wang ; Wei, Zhang ; Takefumi, Ishii ; Sozer, Selcuk ; Jiapeng, Wang ; Mingjiang, Xu ; Hoffman, Ronald. / Correction of the abnormal trafficking of primary myelofibrosis CD34 + cells by treatment with chromatin-modifying agents. In: Cancer Research. 2009 ; Vol. 69, No. 19. pp. 7612-7618.
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