Inverse relationship between myeloid maturation and leukotriene C4 synthase expression in normal and leukemic myelopoiesis—consistent overexpression of the enzyme in myeloid cells from patients with chronic myeloid leukemia

Tornhamre, Susanne; Stenke, Leif; Granzelius, Anna; Sjölinder, Mikael; Näsman-Glaser, Barbro; Roos, Cecilia; Widell, Susanne; Lindgren, Jan

doi:10.1016/s0301-472x(02)01026-3

Cited by 16 publications

(13 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, early observations demonstrated that LTD 4 -stimulate chemotaxis and transendothelial migration of CD34 ϩ hematopoietic progenitor cells (Bautz et al, 2001;Mohle et al, 2003) as well as their proliferation (Braccioni et al, 2002;Parameswaran et al, 2004;Boehmler et al, 2009) and that these activities were suppressed by different CysLT 1 receptor antagonists. Altogether these data indicate a physiological role for cysteinyl LTs as autocrine regulators of hematopoiesis corroborated by the expression of LTC 4 S in immature myeloid cells (Tornhamre et al, 2003).…”

Section: Receptor Expression Patterns With Functional Significancementioning

confidence: 53%

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

Bäck¹,

Dahlén²,

Drazen³

et al. 2011

Pharmacol Rev

130

View full text Add to dashboard Cite

Section: Receptor Expression Patterns With Functional Significancementioning

confidence: 53%

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

Bäck¹,

Dahlén²,

Drazen³

et al. 2011

Pharmacol Rev

130

View full text Add to dashboard Cite

“…However, a later report from the same group showed that the level of leukotriene C4 (LTC4) synthase, which is a key enzyme in the biosynthesis of LTC4 and represents a different metabolic pathway from LTB4, was elevated in human CML cells 39. Therefore, we examined whether BCR-ABL stimulates LTC4 production in CML mice using an ELISA method.…”

Section: Resultsmentioning

confidence: 97%

Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia

et al. 2009

View full text Add to dashboard Cite

Targeting of cancer stem cells is believed to be essential for curative therapy of cancers, but supporting evidence is limited. Few selective target genes in cancer stem cells have been identified. Here we identify the arachidonate 5-lipoxygenase (5-LO) gene (Alox5) as a critical regulator for leukemia stem cells (LSCs) in BCR-ABL-induced chronic myeloid leukemia (CML). In the absence of Alox5, BCR-ABL failed to induce CML in mice. This Alox5 deficiency caused impairment of the function of LSCs but not normal hematopoietic stem cells (HSCs) through affecting differentiation, cell division, and survival of long-term LSCs (LT-LSCs), consequently causing a depletion of LSCs and a failure of CML development. Treatment of CML mice with a 5-LO inhibitor also impaired the function of LSCs similarly by affecting LT-LSCs, and prolonged survival. These results demonstrate that a specific target gene can be found in cancer stem cells and its inhibition can completely inhibit the function of these stem cells.

show abstract

“…No expression of the enzyme at the protein level could be detected in the mature cells, as tested by immunoblot analysis. CML cells showed the same pattern but with constant overexpression when compared with the normal cells (Tornhamre et al , 2003).…”

mentioning

confidence: 77%

Abnormal LTC₄ synthase RNA degradation in neutrophils from CML patients

et al. 2004

Self Cite

View full text Add to dashboard Cite

Summary Neutrophils from patients with chronic myeloid leukaemia (CML) have an aberrant expression of leukotriene (LT)C4 synthase. In order to learn more about the regulation of this abnormality, LTC4 synthase mRNA expression was determined by reverse transcription polymerase chain reaction. A digoxigenin (DIG)‐labelled LTC4 synthase RNA was synthesized and incubated in cytsolic extracts from CML neutrophils, normal neutrophils and eosinophils. LTC4 synthase mRNA was detected in total but not cytoplasmic RNA from normal neutrophils. In contrast, LTC4 synthase mRNA was found in the cytoplasm of CML neutrophils and in normal eosinophils, which also express the enzyme. The DIG‐labelled LTC4 synthase RNA was, as opposed to normal neutrophils, degraded in cytosolic extracts from CML neutrophils. The degradation was time dependent and cell concentration dependent. Degradation was also seen in eosinophils, indicating that degradation of LTC4 synthase RNA was correlated to the expression of the protein. This study showed that the difference in expression of LTC4 synthase in normal and CML neutrophils was not because of a total lack of LTC4 synthase mRNA in normal neutrophils. However normal neutrophils lack, in contrast to CML neutrophils, LTC4 synthase mRNA in the cytoplasm. This discrepancy is not caused by a stabilized LTC4 synthase RNA in the cytosol of CML neutrophils. Instead an abnormal degradation of LTC4 synthase RNA was found in the cytosol of CML neutrophils.

show abstract

Inverse relationship between myeloid maturation and leukotriene C4 synthase expression in normal and leukemic myelopoiesis—consistent overexpression of the enzyme in myeloid cells from patients with chronic myeloid leukemia

Cited by 16 publications

References 56 publications

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia

Abnormal LTC₄ synthase RNA degradation in neutrophils from CML patients

Contact Info

Product

Resources

About

Inverse relationship between myeloid maturation and leukotriene C4 synthase expression in normal and leukemic myelopoiesis—consistent overexpression of the enzyme in myeloid cells from patients with chronic myeloid leukemia

Cited by 16 publications

References 56 publications

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia

Abnormal LTC4 synthase RNA degradation in neutrophils from CML patients

Contact Info

Product

Resources

About

Abnormal LTC₄ synthase RNA degradation in neutrophils from CML patients