Acta Scientific Cancer Biology (ASCB) (ISSN: 2582-4473)

Review Article Volume 7 Issue 7

Normal Hematopoiesis and Hematologic Malignancies: Role of Wnt/β-catenin and PI3K/AKT Cell Signaling Cascades

Armel Hervé Nwabo Kamdje1*, Richard Tagne Simo2 and Hetvet Paulain Dongmo Fogang1

1Department of Physiological Sciences and Biochemistry, Faculty of Medicine and Biomedical Sciences, University of Garoua, Garoua, Cameroon
2Department of Biomedical Sciences, University of Ngaoundere, Cameroon

*Corresponding Author: Armel Hervé Nwabo Kamdje, Department of Physiological Sciences and Biochemistry, Faculty of Medicine and Biomedical Sciences, University of Garoua, Garoua, Cameroon.

Received: July 28, 2023; Published: August 14, 2023

Reprints View PDF Related Articles

Abstract

Wnts are a family of evolutionary-conserved secreted signaling molecules and PI3K-Akt is an intracellular signal transduction. These signaling pathways play significant roles in stromal microenvironment control of the balance between hematopoietic stem cell self-renewal and differentiation. An increasing body of evidence also indicates Wnt and PI3K signaling involvement in the disruption of this balance in hematologic malignancies, where the stromal microenvironment niche favors the infiltration and homing of cancer cells in the bone marrow, as well as leukemia stem cell development and chemoresistance. In the present review, we summarize and discuss the role of the canonical Wnt and PI3K/AKT signaling pathways in normal hematopoiesis and hematologic malignancies, in regards to recent findings on stromal microenvironment involvement in these processes.

 Keywords: Canonical Wnt Signaling Pathway; PI3K-Akt Signaling Pathway; Hematopoiesis; Hematologic Malignancies; Leukemia Stem Cells; Chemoresistance; Cancer

References

  1. Li Z., et al. “The Amotl2 gene inhibits Wnt/beta-catenin signaling and regulates embryonic development in zebrafish”. Journal of Biological Chemistry 287 (2012): 13005-13015.
  2. Chen G., et al. “TGF-beta and BMP signaling in osteoblast differentiation and bone formation”. International Journal of Biological Sciences 8 (2012): 272-288.
  3. Yu S., et al. “The Wnt/β-catenin signaling pathway in Haematological Neoplasms”. Biomark Research 10 (2022): 74.
  4. Malhotra S and Kincade PW. “Wnt-related molecules and signaling pathway equilibrium in hematopoiesis”. Cell Stem Cell 4 (2009): 27-36.
  5. Barker N and Clevers H. “Leucine-rich repeat-containing G-protein-coupled receptors as markers of adult stem cells”. Gastroenterology 138 (2010): 1681-1696.
  6. Carmon KS., et al. “R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling”. Proceedings of the National Academy of Sciences of the United States of America 108 (2011): 11452-11457.
  7. Kornblau SM., et al. “Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia”. Blood 108 (2006): 2358-2365.
  8. Luis TC., et al. “Wnt signaling strength regulates normal hematopoiesis and its deregulation is involved in leukemia development”. Leukemia 26 (2012): 414-421.
  9. Khan NI., et al. “Activation of Wnt/beta-catenin pathway mediates growth and survival in B-cell progenitor acute lymphoblastic leukaemia”. British Journal of Haematology 138 (2007): 338-348.
  10. Luis TC., et al. “Wnt3a deficiency irreversibly impairs hematopoietic stem cell self-renewal and leads to defects in progenitor cell differentiation”. Blood 113 (2009): 546-554.
  11. McGrath EE. “OPG/RANKL/RANK pathway as a therapeutic target in cancer”. Journal of Thoracic Oncology 6 (2011): 1468-1473.
  12. Glass DA., et al. “Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation”. Development Cell 8 (2005): 751-764.
  13. Sabbagh Y., et al. “Repression of osteocyte Wnt/beta-catenin signaling is an early event in the progression of renal osteodystrophy”. The Journal of Bone and Mineral Research (2012).
  14. Lucas D. “Structural organization of the bone marrow and its role in hematopoiesis”. Current Opinion on Hematology 28 (2021): 36-42.
  15. Kokkaliaris K., et al. “Adult blood stem cell localization reflects the abundance of reported bone marrow niche cell types and their combinations”. Blood 136 (2020): 2296-2307.
  16. May M., et al. “Dynamic regulation of hematopoietic stem cells by bone marrow niches”. Current Stem Cell Reports 4 (2018): 201-208.
  17. Ding L., et al. “Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches”. Nature 495 (2013): 231-235.
  18. Calvi LM., et al. “Osteoblastic cells regulate the haematopoietic stem cell niche”. Nature 425 (2003): 841-846.
  19. Zhang J., et al. “Identification of the haematopoietic stem cell niche and control of the niche size”. Nature 425 (2003): 836-841.
  20. Santiago F., et al. “Noncanonical Wnt signaling promotes osteoclast differentiation and is facilitated by the human immunodeficiency virus protease inhibitor ritonavir”. Biochemical and Biophysical Research Communications 417 (2012): 223-230.
  21. Kato M., et al. “Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor”. Journal of Cell Biology 157 (2002): 303-314.
  22. Suda T and Arai F. “Wnt signaling in the niche”. Cell 132 (2008): 729-730.
  23. Luis TC., et al. “Canonical wnt signaling regulates hematopoiesis in a dosage-dependent fashion”. Cell Stem Cell 9 (2011): 345-356.
  24. Kirstetter P., et al. “Activation of the canonical Wnt pathway leads to loss of hematopoietic stem cell repopulation and multilineage differentiation block”. Nature Immunology 7 (2006): 1048-1056.
  25. Fleming HE., et al. “Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo”. Cell Stem Cell 2 (2008): 274-283.
  26. Ichii M., et al. “The canonical Wnt pathway shapes niches supportive of hematopoietic stem/progenitor cells”. Blood 119 (2012): 1683-1692.
  27. Renstrom J., et al. “Secreted frizzled-related protein 1 extrinsically regulates cycling activity and maintenance of hematopoietic stem cells”. Cell Stem Cell 5 (2009): 157-167.
  28. Schaniel C., et al. “Wnt-inhibitory factor 1 dysregulation of the bone marrow niche exhausts hematopoietic stem cells”. Blood 118 (2011): 2420-2429.
  29. Schmidt M., et al. “Targeting Wnt pathway in lymphoma and myeloma cells”. British Journal of Haematology 144 (2009): 796-798.
  30. Raaijmakers MH., et al. “Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia”. Nature 464 (2010): 852-857.
  31. Tripodo C., et al. “The bone marrow stroma in hematological neoplasms--a guilty bystander”. Nature Reviews Clinical Oncology 8 (2011): 456-466.
  32. Iwamoto S., et al. “Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase”. Journal of Clinical Investigation 117 (2007): 1049-1057.
  33. Nwabo Kamdje AH., et al. “Notch-3 and Notch-4 signaling rescue from apoptosis human B-ALL cells in contact with human bone marrow-derived mesenchymal stromal cells”. Blood 118 (2011): 380-389.
  34. Lane SW., et al. “Differential niche and Wnt requirements during acute myeloid leukemia progression”. Blood 118 (2011): 2849-2856.
  35. Mishra A., et al. “Homing of cancer cells to the bone”. Cancer Microenvironment 4 (2011): 221-235.
  36. Fend F and Kremer M. “Diagnosis and classification of malignant lymphoma and related entities in the bone marrow trephine biopsy”. Pathobiology 74 (2007): 133-143.
  37. Vega F., et al. “The stromal composition of malignant lymphoid aggregates in bone marrow: variations in architecture and phenotype in different B-cell tumours”. British Journal of Haematology 117 (2002): 569-576.
  38. Roodman GD. “Mechanisms of bone metastasis”. The New England Journal of Medicine 350 (2004): 1655-1664.
  39. Kondo T., et al. “Wnt signaling promotes neuronal differentiation from mesenchymal stem cells through activation of Tlx3”. Stem Cells