Implications of sphingosine kinase 1 expression level for the cellular sphingolipid rheostat: Relevance as a marker for daunorubicin sensitivity of leukemia cells

S. Sobue, S. Nemoto, M. Murakami, H. Ito, A. Kimura, S. Gao, A. Furuhata, A. Takagi, T. Kojima, M. Nakamura, Y. Ito, M. Suzuki, Y. Banno, Y. Nozawa, T. Murate

Research output: Contribution to journalArticle

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Abstract

We recently reported increased sphingosine kinase 1 (SPHK1) and decreased neutral sphingomyelinase 2 (NSMase2) gene expression in myelodysplastic syndromes and acute leukemia. This alteration is supposed to change the cellular sphingolipid metabolites; however, positive correlations were observed between daunorubicin (DA)-IC50 and the SPHK1 message but not between DA-IC50 and NSMase2 messages, when 16 different leukemia cell lines were used to analyze the relationship between gene expressions and chemosensitivity against DA. Using two cell lines with either the highest or lowest SPHK1 expression, cellular ceramides and sphingosine 1-phosphate (S1P) were quantified by liquid chromatography/mass spectrometry. Increased ceramide was observed in DA-sensitive, but not in DA-resistant cell lines treated with low doses of DA. Upon DA treatment, S1P decreased more in the sensitive cell lines than in resistant cell lines. A SPHK inhibitor recovered the DA sensitivity of DA-resistant cells. The modulation of SPHK1 gene expression by either overexpression or using siRNA affected the DA sensitivity of representative cell lines. Results clearly show that SPHK1 is both a good marker to predict the DA sensitivity of leukemia cells and a potential therapeutic target for leukemia with high SPHK1 expression, and suggest that the sphingolipid rheostat plays a significant role in DA-induced cytotoxicity.

Original languageEnglish
Pages (from-to)266-275
Number of pages10
JournalInternational Journal of Hematology
Volume87
Issue number3
DOIs
Publication statusPublished - 01-04-2008

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Sphingolipids
Daunorubicin
Leukemia
Cell Line
Sphingomyelin Phosphodiesterase
Gene Expression
Inhibitory Concentration 50
sphingosine kinase
Ceramides
Myelodysplastic Syndromes
Liquid Chromatography
Small Interfering RNA
Mass Spectrometry

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Sobue, S. ; Nemoto, S. ; Murakami, M. ; Ito, H. ; Kimura, A. ; Gao, S. ; Furuhata, A. ; Takagi, A. ; Kojima, T. ; Nakamura, M. ; Ito, Y. ; Suzuki, M. ; Banno, Y. ; Nozawa, Y. ; Murate, T. / Implications of sphingosine kinase 1 expression level for the cellular sphingolipid rheostat : Relevance as a marker for daunorubicin sensitivity of leukemia cells. In: International Journal of Hematology. 2008 ; Vol. 87, No. 3. pp. 266-275.
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abstract = "We recently reported increased sphingosine kinase 1 (SPHK1) and decreased neutral sphingomyelinase 2 (NSMase2) gene expression in myelodysplastic syndromes and acute leukemia. This alteration is supposed to change the cellular sphingolipid metabolites; however, positive correlations were observed between daunorubicin (DA)-IC50 and the SPHK1 message but not between DA-IC50 and NSMase2 messages, when 16 different leukemia cell lines were used to analyze the relationship between gene expressions and chemosensitivity against DA. Using two cell lines with either the highest or lowest SPHK1 expression, cellular ceramides and sphingosine 1-phosphate (S1P) were quantified by liquid chromatography/mass spectrometry. Increased ceramide was observed in DA-sensitive, but not in DA-resistant cell lines treated with low doses of DA. Upon DA treatment, S1P decreased more in the sensitive cell lines than in resistant cell lines. A SPHK inhibitor recovered the DA sensitivity of DA-resistant cells. The modulation of SPHK1 gene expression by either overexpression or using siRNA affected the DA sensitivity of representative cell lines. Results clearly show that SPHK1 is both a good marker to predict the DA sensitivity of leukemia cells and a potential therapeutic target for leukemia with high SPHK1 expression, and suggest that the sphingolipid rheostat plays a significant role in DA-induced cytotoxicity.",
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Sobue, S, Nemoto, S, Murakami, M, Ito, H, Kimura, A, Gao, S, Furuhata, A, Takagi, A, Kojima, T, Nakamura, M, Ito, Y, Suzuki, M, Banno, Y, Nozawa, Y & Murate, T 2008, 'Implications of sphingosine kinase 1 expression level for the cellular sphingolipid rheostat: Relevance as a marker for daunorubicin sensitivity of leukemia cells', International Journal of Hematology, vol. 87, no. 3, pp. 266-275. https://doi.org/10.1007/s12185-008-0052-0

Implications of sphingosine kinase 1 expression level for the cellular sphingolipid rheostat : Relevance as a marker for daunorubicin sensitivity of leukemia cells. / Sobue, S.; Nemoto, S.; Murakami, M.; Ito, H.; Kimura, A.; Gao, S.; Furuhata, A.; Takagi, A.; Kojima, T.; Nakamura, M.; Ito, Y.; Suzuki, M.; Banno, Y.; Nozawa, Y.; Murate, T.

In: International Journal of Hematology, Vol. 87, No. 3, 01.04.2008, p. 266-275.

Research output: Contribution to journalArticle

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T1 - Implications of sphingosine kinase 1 expression level for the cellular sphingolipid rheostat

T2 - Relevance as a marker for daunorubicin sensitivity of leukemia cells

AU - Sobue, S.

AU - Nemoto, S.

AU - Murakami, M.

AU - Ito, H.

AU - Kimura, A.

AU - Gao, S.

AU - Furuhata, A.

AU - Takagi, A.

AU - Kojima, T.

AU - Nakamura, M.

AU - Ito, Y.

AU - Suzuki, M.

AU - Banno, Y.

AU - Nozawa, Y.

AU - Murate, T.

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