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Dissecting the role of SALL4, a newly identified stem cell factor, in chronic myelogenous leukemia

Leukemia volume 25, pages 1211–1213 (2011)Cite this article

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Chronic myelogenous leukemia (CML) is a hematological malignancy that expresses the BCR–ABL fusion oncogene. It has three distinct clinicopathological phases: chronic phase, accelerated phase and blast crisis. Tyrosine kinase inhibitors, which target the BCR–ABL fusion protein, can induce complete cytogenic remission in more than 70% of newly diagnosed chronic CML patients. However, complete molecular response is a rare event in these CML patients with complete cytogenic remission, suggesting that they are not effective in eliminating CML leukemia-initiating cells (LIC), although there are differences between the trosine kinase inhibitors. Once CML progresses to blast crisis, it becomes resistant to most treatment approaches, and survival rapidly declines. The exact underlying mechanism of transformation of chronic phase CML to blast crisis is still unclear; however, it is thought to be supported by self-renewing LIC. Therefore, identifying genes or signaling pathways involved in the self-renewal of LIC may promote more effective leukemia treatments. So far, two key regulators in self-renewal of LIC have been linked to CML progression, Wnt/β-catenin and Bmi-1.1, 2, 3, 4

Recently, several research groups, including ours, have demonstrated that SALL4 has an essential role in the maintenance of pluripotent and self-renewal properties of embryonic stem cells by interacting with Nanog and Oct4.5 In addition, our group has shown that constitutive expression of SALL4 contributes to leukemogenesis in adult mice by interacting with two other key regulators in LIC, Wnt/β-catenin and Bmi-1.6, 7 It seems that SALL4 is a unique gene involved in self-renewal in embryonic stem cells and LIC. Therefore, we examined SALL4 expression in CML to determine whether it could be involved in the pathogenesis of this disease.

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References

  1. Jamieson CH, Ailles LE, Dylla SJ, Muijtjens M, Jones C, Zehnder JL et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med 2004; 351: 657–667.

    Article  CAS  Google Scholar 

  2. Mohty M, Yong AS, Szydlo RM, Apperley JF, Melo JV . The polycomb group BMI1 gene is a molecular marker for predicting prognosis of chronic myeloid leukemia. Blood 2007; 110: 380–383.

    Article  CAS  Google Scholar 

  3. Raaphorst FM . Self-renewal of hematopoietic and leukemic stem cells: a central role for the Polycomb-group gene Bmi-1. Trends Immunol 2003; 24: 522–524.

    Article  CAS  Google Scholar 

  4. Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 2003; 423: 302–305.

    Article  CAS  Google Scholar 

  5. Zhang J, Tam WL, Tong GQ, Wu Q, Chan HY, Soh BS et al. Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1. Nat Cell Biol 2006; 8: 1114–1123.

    Article  CAS  Google Scholar 

  6. Yang J, Chai L, Liu F, Fink LM, Lin P, Silberstein LE et al. Bmi-1 is a target gene for SALL4 in hematopoietic and leukemic cells. Proc Natl Acad Sci USA 2007; 104: 10494–10499.

    Article  CAS  Google Scholar 

  7. Ma Y, Cui W, Yang J, Qu J, Di C, Amin HM et al. SALL4, a novel oncogene, is constitutively expressed in human acute myeloid leukemia (AML) and induces AML in transgenic mice. Blood 2006; 108: 2726–2735.

    Article  CAS  Google Scholar 

  8. Li S, Ilaria Jr RL, Million RP, Daley GQ, Van Etten RA . The P190, P210, and P230 forms of the BCR/ABL oncogene induce a similar chronic myeloid leukemia-like syndrome in mice but have different lymphoid leukemogenic activity. J Exp Med 1999; 189: 1399–1412.

    Article  CAS  Google Scholar 

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Author notes

  1. J Lu, Y Ma and L E Silberstein: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Brigham and Women's Hospital, Harvard Medical School Boston, Boston, MA, USA

    J Lu, N Kong, C Gao, L E Silberstein & L Chai

  2. Department of Pathology, Stony Brook University Medical Center, Stony Brook, NY, USA

    Y Ma

  3. Division of Laboratory Medicine, Nevada Cancer Institute, 10441 W Twain Avenue, Las Vegas, NV, USA

    Y Ma & Z Alipio

  4. Department of Pathology, Blood Transfusion Service, Massachusetts General Hospital, 55 Fruit St. Boston, Boston, MA, USA

    D S Krause

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  1. J Lu
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Correspondence to L Chai.

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Competing interests

This work was supported in part through NIH grants NIH R01HL087948 (to Dr Yupo Ma), RO1HL092437, RO1HL092437-A1S1, PO1 DK080665 (to Dr Li Chai) and PO1HL095489 (to Dr Li Chai and Leslie Silberstein).

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Lu, J., Ma, Y., Kong, N. et al. Dissecting the role of SALL4, a newly identified stem cell factor, in chronic myelogenous leukemia. Leukemia 25, 1211–1213 (2011). https://doi.org/10.1038/leu.2011.65

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