Skip to main content

Advertisement

SpringerLink
Log in

New insights in cellular and molecular aspects of BM niche in chronic myelogenous leukemia

  • Review
  • Published:
Tumor Biology

Abstract

Hematoproliferative neoplasias like chronic myelogenous leukemia (CML) progressively affect bone marrow niche; however, there are only few specific clinical markers for prediction of disease progression. Here, we review the myeloproliferative niche and molecular changes including signaling pathways as well as microRNA (miRNA) in CML in order to better understand the therapeutic approaches. CML is a three-stage myeloproliferative disorder caused by reciprocal translocation between chromosome 9 and 22. There has been a new interest on treatment of this disorder. Therefore, in order to develop the appropriate therapy, an analysis of the molecular changes involved in malignant cells can be effective. A review of the signaling pathways, miRNA, and related targets can be helpful for better understanding of molecular pathogenesis of CML. Characterizing malignant cells and molecular changes with a focus on their targets may help researchers use molecular targets as effective therapeutic means for CML. On the other hand, interactions between leukemic stem cells and CML niche will help researchers investigate the causes of drug resistance in this disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Celso CL, Fleming HE, Wu JW, Zhao CX, Miake-Lye S, Fujisaki J, et al. Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche. Nature. 2009;457(7225):92–6.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Azizidoost S, Babashah S, Rahim F, Shahjahani M, Saki N. Bone marrow neoplastic niche in leukemia. Hematology. 2014;19(4):232–8.

    Article  CAS  PubMed  Google Scholar 

  3. Yasumizu R, Toki J, Asou H, Nishino T, Komatsu Y, Ikehara S. Production of hematopoietic stem cell-chemotactic factor by bone marrow stromal cells. Blood. 1994;83(4):964–71.

    PubMed  Google Scholar 

  4. Williams DA, Cancelas JA. Leukaemia: niche retreats for stem cells. Nature. 2006;444(7121):827–8.

    Article  CAS  PubMed  Google Scholar 

  5. Saki N, Abroun S, Farshdousti Hagh M, Asgharei F. Neoplastic bone marrow niche: hematopoietic and mesenchymal stem cells. Cell J. 2011;13(3):131–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Azizidoost S, Shanaki Bavarsad M, Shanaki Bavarsad M, Shahrabi S, Jaseb K, Rahim F, et al. The role of notch signaling in bone marrow niche. Hematology. 2014. doi:10.1179/1607845414y.0000000167.

  7. Schepers K, Pietras EM, Reynaud D, Flach J, Binnewies M, Garg T, et al. Myeloproliferative neoplasia remodels the endosteal bone marrow niche into a self-reinforcing leukemic niche. Cell Stem Cell. 2013;13(3):285–99.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Oehler VG, Yeung KY, Choi YE, Bumgarner RE, Raftery AE, Radich JP. The derivation of diagnostic markers of chronic myeloid leukemia progression from microarray data. Blood. 2009;114(15):3292–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Nwajei F, Konopleva M. The bone marrow microenvironment as niche retreats for hematopoietic and leukemic stem cells. Adv Hematol. 2013;2013.

  10. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. New Engl J Med. 2001;344(14):1031–7.

    Article  CAS  PubMed  Google Scholar 

  11. Gordon JE, Wong JJL, Rasko JE. MicroRNAs in myeloid malignancies. Br J Haematol. 2013;162(2):162–76.

    Article  CAS  PubMed  Google Scholar 

  12. Flamant S, Ritchie W, Guilhot J, Holst J, Bonnet ML, Chomel JC, et al. Micro-RNA response to imatinib mesylate in patients with chronic myeloid leukemia. Haematologica. 2010;95(8):1325–33.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Sipkins DA, Wei X, Wu JW, Runnels JM, Cote D, Means TK, et al. In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment. Nature. 2005;435(7044):969–73.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Agirre X, Jiménez-Velasco A, San José-Enériz E, Garate L, Bandrés E, Cordeu L, et al. Down-regulation of hsa-miR-10a in chronic myeloid leukemia CD34+ cells increases USF2-mediated cell growth. Mol Cancer Res. 2008;6(12):1830–40.

    Article  CAS  PubMed  Google Scholar 

  15. Melo JV, Deininger MW. Biology of chronic myelogenous leukemia-signaling pathways of initiation and transformation. Hematol Oncol Clin North Am. 2004;18(3):545–68.

    Article  PubMed  Google Scholar 

  16. Ahmed W, Van Etten RA. Signal transduction in the chronic leukemias: implications for targeted therapies. Curr Hematol Malig Rep. 2013;8(1):71–80.

    Article  PubMed  Google Scholar 

  17. Zhang B, Ho YW, Huang Q, Maeda T, Lin A, S-u L, et al. Altered microenvironmental regulation of leukemic and normal stem cells in chronic myelogenous leukemia. Cancer Cell. 2012;21(4):577–92.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Krause DS, Lazarides K, von Andrian UH, Van Etten RA. Requirement for CD44 in homing and engraftment of BCR-ABL-expressing leukemic stem cells. Nat Med. 2006;12(10):1175–80.

    Article  CAS  PubMed  Google Scholar 

  19. Ninomiya S, Kanemura N, Tsurumi H, Kasahara S, Hara T, Yamada T, et al. Coexistence of inversion 16 and the Philadelphia chromosome comprising P190 BCR/ABL in chronic myeloid leukemia blast crisis. Int J Hematol. 2011;93(6):806–10.

    Article  PubMed  Google Scholar 

  20. Werner M, Kaloutsi V, Buhr T, Delventhal S, Vykoupil K-F, Georgii A. Cytogenetics of chronic myelogenous leukemia (CML) correlated to the histopathology of bone marrow biopsies. Ann Hematol. 1991;63(4):201–5.

    Article  CAS  PubMed  Google Scholar 

  21. Van der Plas D, Grosveld G, Hagemeijer A. Review of clinical, cytogenetic, and molecular aspects of Ph-negative CML. Cancer Genet Cytogenet. 1991;52(2):143–56.

    Article  PubMed  Google Scholar 

  22. Provan A, Majer RV, Herbert A, Smith AG. del (15) (q11q15) associated with transformation of chronic myelomonocytic leukemia. Cancer Genet Cytogenet. 1991;55(1):35–8.

    Article  CAS  PubMed  Google Scholar 

  23. Wessels J, Fibbe W, Van Der Keur D, Landegent J, Van Der Plas D, Den Ottolander G, et al. t(5; 12)(q31; p12). A clinical entity with features of both myeloid leukemia and chronic myelomonocytic leukemia. Cancer Genet Cytogenet. 1993;65(1):7–11.

    Article  CAS  PubMed  Google Scholar 

  24. Sherrington P, Nacheva E, Fischer P, Rees J, Hoyle C, Dyer M, et al. Translocation 5;21 and interstitial deletion of chromosome 7 in a case of chronic myelomonocytic leukemia. Cancer Genet Cytogenet. 1988;31(2):247–52.

    Article  CAS  PubMed  Google Scholar 

  25. Medeiros BC, Markovic V, Kamel-Reid S, Lipton JH. Presence of t(1;14)(p13;p11.2) in Philadelphia chromosome-negative cells in a patient with chronic myeloid leukemia. Cancer Genet Cytogenet. 2007;173(1):83–4.

    Article  CAS  PubMed  Google Scholar 

  26. Thompson P, Whittaker J. Translocation 3;21 in Philadelphia chromosome positive chronic myeloid leukemia at diagnosis. Cancer Genet Cytogenet. 1989;39(2):143–6.

    Article  CAS  PubMed  Google Scholar 

  27. Vaidya S, Joshi D, Ghosh K, Chakrabarti P, Vundinti BR. A novel 5-way translocation t(9;11;13;19;22) in a case of chronic-phase chronic myeloid leukemia. Hum Pathol. 2013;44(10):2365–9.

    Article  CAS  PubMed  Google Scholar 

  28. Gerber JM, Qin L, Kowalski J, Smith BD, Griffin CA, Vala MS, et al. Characterization of chronic myeloid leukemia stem cells. Am J Hematol. 2011;86(1):31–7.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Gerber JM, Gucwa JL, Esopi D, Gurel M, Haffner MC, Vala M, et al. Genome-wide comparison of the transcriptomes of highly enriched normal and chronic myeloid leukemia stem and progenitor cell populations. Oncotarget. 2013;4(5):715.

    PubMed Central  PubMed  Google Scholar 

  30. Naka K, Hoshii T, Muraguchi T, Tadokoro Y, Ooshio T, Kondo Y, et al. TGF-β–FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia. Nature. 2010;463(7281):676–80.

    Article  CAS  PubMed  Google Scholar 

  31. Corrêa S, Binato R, Du Rocher B, Castelo-Branco MT, Pizzatti L, Abdelhay E. Wnt/β-catenin pathway regulates ABCB1 transcription in chronic myeloid leukemia. BMC Cancer. 2012;12(1):303.

    Article  PubMed Central  PubMed  Google Scholar 

  32. Sengupta A, Banerjee D, Chandra S, Banerji S, Ghosh R, Roy R, et al. Deregulation and cross talk among Sonic hedgehog, Wnt, Hox and Notch signaling in chronic myeloid leukemia progression. Leukemia. 2007;21(5):949–55.

    CAS  PubMed  Google Scholar 

  33. Danisz K, Blasiak J. Role of anti-apoptotic pathways activated by BCR/ABL in the resistance of chronic myeloid leukemia cells to tyrosine kinase inhibitors. Acta Biochim Pol. 2013;60:503–14.

    PubMed  Google Scholar 

  34. Yang Z, Yang C, Zhang S, Li Y, Chen J. Notch2 inhibits proliferation of chronic myeloid leukemia cells. Oncol Lett. 2013;5(4):1390–4.

    CAS  PubMed Central  PubMed  Google Scholar 

  35. Chang G, Zhang H, Wang J, Zhang Y, Xu H, Wang C, et al. CD44 targets Wnt/β-catenin pathway to mediate the proliferation of K562 cells. Cancer Cell Int. 2013;13(1):117.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Helgason GV, Young GA, Holyoake TL. Targeting chronic myeloid leukemia stem cells. Curr Hematol Malig Rep. 2010;5(2):81–7.

    Article  PubMed  Google Scholar 

  37. Zhang L, Huang J, Yang N, Greshock J, Megraw MS, Giannakakis A, et al. microRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci. 2006;103(24):9136–41.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Bueno MJ, Perez de Castro I, Gomez de Cedron M, Santos J, Calin GA, Cigudosa JC, et al. Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell. 2008;13(6):496–506.

    Article  CAS  PubMed  Google Scholar 

  39. Polakova KM, Lopotová T, Klamová H, Burda P, Trněný M, Stopka T, et al. Expression patterns of microRNAs associated with CML phases and their disease related targets. Mol Cancer. 2011;10(1):41–53.

    Article  CAS  Google Scholar 

  40. Eiring AM, Harb JG, Neviani P, Garton C, Oaks JJ, Spizzo R, et al. miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell. 2010;140(5):652–65.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Albano F, Anelli L, Zagaria A, Liso V, Rocchi M, Specchia G. MIRN199B downregulation in chronic myeloid leukaemia is associated with deletions on der(9). Br J Haematol. 2009;144(2):271–3.

    Article  PubMed  Google Scholar 

  42. Kong W, He L, Richards E, Challa S, Xu C, Permuth-Wey J, et al. Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer. Oncogene. 2013;33(6):679–89.

    Article  PubMed Central  PubMed  Google Scholar 

  43. San José-Enériz E, Román-Gómez J, Jiménez-Velasco A, Garate L, Martin V, Cordeu L, et al. MicroRNA expression profiling in imatinib-resistant chronic myeloid leukemia patients without clinically significant ABL1-mutations. Mol Cancer. 2009;8(1):69–72.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Zhu X, Lin Z, Du J, Zhou X, Yang L, Liu G. Studies on microRNAs that are correlated with the cancer stem cells in chronic myeloid leukemia. Mol Cell Biochem. 2014;390(1–2):75–84.

    Article  CAS  PubMed  Google Scholar 

  45. Babashah S, Sadeghizadeh M, Hajifathali A, Tavirani MR, Zomorod MS, Ghadiani M, et al. Targeting of the signal transducer Smo links microRNA‐326 to the oncogenic Hedgehog pathway in CD34+ CML stem/progenitor cells. Int J Cancer. 2013;133(3):579–89.

    Article  CAS  PubMed  Google Scholar 

  46. Venturini L, Battmer K, Castoldi M, Schultheis B, Hochhaus A, Muckenthaler MU, et al. Expression of the miR-17–92 polycistron in chronic myeloid leukemia (CML) CD34+ cells. Blood. 2007;109(10):4399–405.

    Article  CAS  PubMed  Google Scholar 

  47. Li Y, Wang H, Tao K, Xiao Q, Huang Z, Zhong L, et al. miR-29b suppresses CML cell proliferation and induces apoptosis via regulation of BCR/ABL1 protein. Exp Cell Res. 2013;319(8):1094–101.

    Article  CAS  PubMed  Google Scholar 

  48. Yin H, Liu Y, Zheng W-L, Song Y-B. Effects of miRNA-196b overexpression on proliferation, apoptosis and survivin, Cox-2 expression of K562 cells. China Oncol. 2013;5:007.

    Google Scholar 

  49. Labbaye C, Testa U. The emerging role of MIR-146A in the control of hematopoiesis, immune function and cancer. J Hematol Oncol. 2012;5(1):13.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Chomel J, Aggoune D, Sorel N, Turhan A. [Chronic myeloid leukemia stem cells: cross-talk with the niche]. Med Sci: M/S. 2014;30(4):452–61.

    Google Scholar 

  51. Corrado C, Raimondo S, Saieva L, Flugy AM, De Leo G, Alessandro R. Exosome-mediated crosstalk between chronic myelogenous leukemia cells and human bone marrow stromal cells triggers an interleukin 8-dependent survival of leukemia cells. Cancer Lett. 2014;348(1):71–6.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We wish to thank all our colleagues in Shafa Hospital and Allied Health Sciences School, Ahvaz Jundishapur University of Medical Sciences.

Authors’ contributions

N. S. and Sh. A. conceived the manuscript and revised it; S. Sh., F. R., and M. Sh. wrote the manuscript. N. S and A. A. prepared the tables.

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of Biochemistry and Hematology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran

    Saeid Shahrabi & Fakher Rahim

  2. Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Shirin Azizidoost, Mohammad Shahjahani, Ahmad Ahmadzadeh & Najmaldin Saki

Authors
  1. Saeid Shahrabi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shirin Azizidoost
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammad Shahjahani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fakher Rahim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ahmad Ahmadzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Najmaldin Saki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Najmaldin Saki.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shahrabi, S., Azizidoost, S., Shahjahani, M. et al. New insights in cellular and molecular aspects of BM niche in chronic myelogenous leukemia. Tumor Biol. 35, 10627–10633 (2014). https://doi.org/10.1007/s13277-014-2610-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2610-9

Keywords

Search

Navigation