RIZ1 is potential CML tumor suppressor that is down-regulated during disease progression

Ashakumary Lakshmikuttyamma, Naoto Takahashi, Elodie Pastural, Emina Torlakovic, Hesham M. Amin, Guillermo Garcia-Manero, Michael Voralia, Magdalena Czader, John F. Decoteau, C. Ronald Geyer

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background. RIZ1 expression and activity are reduced in many cancers. In AML cell lines and patient material, RIZ1 expression is reduced relative to normal bone marrow. In chronic myelogenous leukemia (CML), blastic transformation is associated with loss of heterozygosity in the region where RIZ1 is located. RIZ1 is a PR domain methyltransferase that methylates histone H3 lysine 9, a modification important for transcriptional repression. In CML blast crisis cell lines RIZ1 represses insulin-like growth factor-1 expression and autocrine signaling. Together these observations suggest that RIZ1 may have a role in the chronic phase to blast crisis transition in CML. Results. In CML patient material, we observed that RIZ1 expression was decreased during progression from chronic phase to blast crisis. RIZ1 was expressed in mature myeloid and CD34 cells demonstrating that decreased RIZ1 expression in blast crisis is not due to an increased immature cell population. Expression of RIZ1 CML blast crisis cell lines decreased proliferation, increased apoptosis, and enhanced differentiation. Conclusion. RIZ1 is a candidate tumor suppressor gene whose expression is decreased in blast crisis. Loss of RIZ1 activity results in decreased apoptosis and differentiation and enhanced proliferation. Together these results suggest that loss of RIZ1 expression will lead to an increase in myeloid blast cell population resulting in CML progression.

Original languageEnglish (US)
Article number28
JournalJournal of Hematology and Oncology
Volume2
DOIs
StatePublished - 2009
Externally publishedYes

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Blast Crisis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Disease Progression
Neoplasms
Myeloid Cells
Cell Line
Autocrine Communication
Apoptosis
Loss of Heterozygosity
Somatomedins
Tumor Suppressor Genes
Population
Lysine
Bone Marrow
Gene Expression

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research
  • Molecular Biology
  • Medicine(all)

Cite this

Lakshmikuttyamma, A., Takahashi, N., Pastural, E., Torlakovic, E., Amin, H. M., Garcia-Manero, G., ... Geyer, C. R. (2009). RIZ1 is potential CML tumor suppressor that is down-regulated during disease progression. Journal of Hematology and Oncology, 2, [28]. https://doi.org/10.1186/1756-8722-2-28

RIZ1 is potential CML tumor suppressor that is down-regulated during disease progression. / Lakshmikuttyamma, Ashakumary; Takahashi, Naoto; Pastural, Elodie; Torlakovic, Emina; Amin, Hesham M.; Garcia-Manero, Guillermo; Voralia, Michael; Czader, Magdalena; Decoteau, John F.; Geyer, C. Ronald.

In: Journal of Hematology and Oncology, Vol. 2, 28, 2009.

Research output: Contribution to journalArticle

Lakshmikuttyamma, A, Takahashi, N, Pastural, E, Torlakovic, E, Amin, HM, Garcia-Manero, G, Voralia, M, Czader, M, Decoteau, JF & Geyer, CR 2009, 'RIZ1 is potential CML tumor suppressor that is down-regulated during disease progression', Journal of Hematology and Oncology, vol. 2, 28. https://doi.org/10.1186/1756-8722-2-28
Lakshmikuttyamma A, Takahashi N, Pastural E, Torlakovic E, Amin HM, Garcia-Manero G et al. RIZ1 is potential CML tumor suppressor that is down-regulated during disease progression. Journal of Hematology and Oncology. 2009;2. 28. https://doi.org/10.1186/1756-8722-2-28
Lakshmikuttyamma, Ashakumary ; Takahashi, Naoto ; Pastural, Elodie ; Torlakovic, Emina ; Amin, Hesham M. ; Garcia-Manero, Guillermo ; Voralia, Michael ; Czader, Magdalena ; Decoteau, John F. ; Geyer, C. Ronald. / RIZ1 is potential CML tumor suppressor that is down-regulated during disease progression. In: Journal of Hematology and Oncology. 2009 ; Vol. 2.
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abstract = "Background. RIZ1 expression and activity are reduced in many cancers. In AML cell lines and patient material, RIZ1 expression is reduced relative to normal bone marrow. In chronic myelogenous leukemia (CML), blastic transformation is associated with loss of heterozygosity in the region where RIZ1 is located. RIZ1 is a PR domain methyltransferase that methylates histone H3 lysine 9, a modification important for transcriptional repression. In CML blast crisis cell lines RIZ1 represses insulin-like growth factor-1 expression and autocrine signaling. Together these observations suggest that RIZ1 may have a role in the chronic phase to blast crisis transition in CML. Results. In CML patient material, we observed that RIZ1 expression was decreased during progression from chronic phase to blast crisis. RIZ1 was expressed in mature myeloid and CD34 cells demonstrating that decreased RIZ1 expression in blast crisis is not due to an increased immature cell population. Expression of RIZ1 CML blast crisis cell lines decreased proliferation, increased apoptosis, and enhanced differentiation. Conclusion. RIZ1 is a candidate tumor suppressor gene whose expression is decreased in blast crisis. Loss of RIZ1 activity results in decreased apoptosis and differentiation and enhanced proliferation. Together these results suggest that loss of RIZ1 expression will lead to an increase in myeloid blast cell population resulting in CML progression.",
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AU - Lakshmikuttyamma, Ashakumary

AU - Takahashi, Naoto

AU - Pastural, Elodie

AU - Torlakovic, Emina

AU - Amin, Hesham M.

AU - Garcia-Manero, Guillermo

AU - Voralia, Michael

AU - Czader, Magdalena

AU - Decoteau, John F.

AU - Geyer, C. Ronald

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AB - Background. RIZ1 expression and activity are reduced in many cancers. In AML cell lines and patient material, RIZ1 expression is reduced relative to normal bone marrow. In chronic myelogenous leukemia (CML), blastic transformation is associated with loss of heterozygosity in the region where RIZ1 is located. RIZ1 is a PR domain methyltransferase that methylates histone H3 lysine 9, a modification important for transcriptional repression. In CML blast crisis cell lines RIZ1 represses insulin-like growth factor-1 expression and autocrine signaling. Together these observations suggest that RIZ1 may have a role in the chronic phase to blast crisis transition in CML. Results. In CML patient material, we observed that RIZ1 expression was decreased during progression from chronic phase to blast crisis. RIZ1 was expressed in mature myeloid and CD34 cells demonstrating that decreased RIZ1 expression in blast crisis is not due to an increased immature cell population. Expression of RIZ1 CML blast crisis cell lines decreased proliferation, increased apoptosis, and enhanced differentiation. Conclusion. RIZ1 is a candidate tumor suppressor gene whose expression is decreased in blast crisis. Loss of RIZ1 activity results in decreased apoptosis and differentiation and enhanced proliferation. Together these results suggest that loss of RIZ1 expression will lead to an increase in myeloid blast cell population resulting in CML progression.

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