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CD244 maintains the proliferation ability of leukemia initiating cells through SHP-2/p27kip1 signaling

Feifei Zhang1, Xiaoye Liu1, Chiqi Chen1

  • 1Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, China.

Haematologica
|January 28, 2017
PubMed

Insights

CD244, a surface immune molecule, is highly expressed on leukemia initiating cells. Targeting CD244 impairs leukemia cell proliferation without affecting normal stem cells, suggesting it as a novel therapeutic target for acute myeloid leukemia.

Area of Science:

  • Immunology
  • Hematology
  • Cancer Biology

Background:

  • Targeting leukemia initiating cells (LICs) is crucial for leukemia cure.
  • Identifying novel therapeutic targets for LICs is a key research area.
  • CD244, known for its role in natural killer cells, has an uncharacterized function in leukemia.

Purpose of the Study:

  • To investigate the role of CD244 in leukemia initiating cells.
  • To determine if CD244 is a potential therapeutic target for leukemia.

Main Methods:

  • CD244 expression analysis in mouse and human leukemia cells.
  • CD244 knockdown experiments in vitro and in vivo.
  • Analysis of hematopoietic stem cell repopulation.
  • Murine acute myeloid leukemia model (MLL-AF9) with CD244 deletion.
  • Mechanistic studies involving protein-protein interactions and signaling pathways (c-Kit, p27, SHP-2).

Main Results:

  • CD244 is highly expressed on both mouse and human LICs.
  • CD244 knockdown significantly impairs leukemia cell proliferation in vitro and in vivo.
  • CD244 knockdown does not affect the repopulation ability of hematopoietic stem cells.
  • CD244 deletion delays leukemogenesis and reduces leukemia initiating cell populations in a murine AML model.
  • CD244 interacts with c-Kit and p27, activating SHP-2 signaling to promote leukemia development.

Conclusions:

  • CD244 plays a critical role in maintaining the stemness of leukemia initiating cells.
  • CD244 is essential for leukemia development but not for normal hematopoietic stem cell function.
  • CD244 represents a promising novel therapeutic target for acute myeloid leukemia.

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