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Differential expression of Sonic hedgehog and Gli1 in hematological malignancies

Leukemia volume 22, pages 226–228 (2008)Cite this article

Hedgehog (Hh) proteins are a family of intercellular signaling molecules. They are originally identified as a polarization gene required for embryonic patterning in Drosophila.1 Sonic hedgehog homolog (Shh) gene is studied more thoroughly among three mammalian homologs. Shh regulates a wide range of developmental processes in tissues, including skin, nervous system, foregut, lung, limbs, pituitary gland and pancreas.2 In terms of tumorigenesis, it has been described that Ptc, a gene encoding a protein as the receptor of Shh, behaves as a tumor suppressor gene, and Smo as well as its downstream signaling Gli genes are oncogenic.3 Medulloblastoma and basal cell carcinoma are malignancies most associated with the hedgehog pathway. In addition, Shh pathway has also been reported to play an important role in the malignant potential of small cell lung cancer and cancers of stomach, esophagus, pancreas, biliary tract, prostate gland and human intestinal stromal tumors.3

Some studies have demonstrated an important role for Shh pathway in the regulation of proliferation of primitive human hematopoietic cells,4 in early lymphoid cell differentiation5 and in cytokine production and promoting cell cycle progression in activated peripheral CD4+ T lymphocytes.6 Bhardwaj et al.4 had demonstrated that Shh induced proliferation of primitive human hematopoietic cells via mechanisms that were dependent on downstream bone morphogenetic protein signals. Shh and its receptors Ptc and Smo were expressed in primitive and mature CD34+CD38+Lin− and mature CD19+, CD33+ and CD3+ cell populations. There are evidences suggesting a role for Shh pathway in early lymphoid cell development and differentiation.5 Shh pathway also plays a role in cytokine production and in promoting cell cycle progression in activated peripheral CD4+ T lymphocytes.6 With regards to B lymphocyte, Sacedon et al.7 found that Shh produced by follicular dendritic cells could protect the survival and function of germinal center B cells. Detmer et al.8 suggested that the hedgehog signaling pathway was involved in the control of hematopoietic differentiation, especially in erythropoiesis. Albeit evidences suggesting the implication of Shh pathway in the hematopoiesis and immune system, there is little evidence to demonstrate its relation to hematological malignancy.

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Acknowledgements

This work was supported in part by a grant from China Medical University (Taichung, Taiwan) Research Grant DMR-96-107.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

    L-Y Bai & C-F Chiu

  2. Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan

    L-Y Bai, C-F Chiu & M-C Kao

  3. Department of Medical Technology, College of Health Care, China Medical University, Taichung, Taiwan

    C-W Lin

  4. Department of Surgery, China Medical University Hospital, Taichung, Taiwan

    N-Y Hsu

  5. Department of Medical Research, Stem Cell Research Laboratory, China Medical University Hospital, Taichung, Taiwan

    C-L Lin & W-J Lo

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Correspondence to M-C Kao.

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Bai, LY., Chiu, CF., Lin, CW. et al. Differential expression of Sonic hedgehog and Gli1 in hematological malignancies. Leukemia 22, 226–228 (2008). https://doi.org/10.1038/sj.leu.2404978

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