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Expression of the Aldo-Ketoreductases AKR1B1 and AKR1B10 in Human Cancers.

Laffin B, Petrash JM - Front Pharmacol (2012)

Bottom Line: Using this database, we found that expression of AKR1B1 and AKR1B10 varies greatly by cancer type and tissue of origin, including agreement with previous reports that AKR1B10 is significantly over-expressed in cancers of the lungs and liver.AKR1B1 over-expression was found to be associated with shortened patient survival in acute myelogenous leukemias and multiple myelomas.High AKR1B10 expression tends to predict less aggressive clinical course generally, notably within lung cancers, where it tends to be highly over-expressed compared to normal tissue.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, The School of Medicine, University of Colorado Aurora, CO, USA.

ABSTRACT
The American Cancer Society estimates that there will be more than 1.5 million new cases of cancer in 2011, underscoring the need for identification of new therapeutic targets and development of novel cancer therapies. Previous studies have implicated the human aldo-ketoreductases AKR1B1 and AKR1B10 in cancer, and therefore we examined AKR1B1 and AKR1B10 expression across all major human cancer types using the Oncomine cancer gene expression database (Compendia Biosciences, www.oncomine.com). Using this database, we found that expression of AKR1B1 and AKR1B10 varies greatly by cancer type and tissue of origin, including agreement with previous reports that AKR1B10 is significantly over-expressed in cancers of the lungs and liver. AKR1B1 is more broadly over-expressed in human cancers than AKR1B10, albeit at a generally lower magnitude. AKR1B1 over-expression was found to be associated with shortened patient survival in acute myelogenous leukemias and multiple myelomas. High AKR1B10 expression tends to predict less aggressive clinical course generally, notably within lung cancers, where it tends to be highly over-expressed compared to normal tissue. These findings suggest that AKR1B1 inhibitors in particular hold great potential as novel cancer therapeutics.

No MeSH data available.


Related in: MedlinePlus

AKR1B1 expression by gene fusion status in leukemia patients. AKR1B1 mRNA expression in leukemia patients with specific gene fusions and chromosomal rearrangements was compared to corresponding leukemia patients without the fusion across all leukemia types and for all such events where Oncomine contained multiple studies with such data. The heatmaps represent the relative expression in patients with the indicated fusions compared to those without, with red indicating over-expression in patients bearing the fusion and blue under-expression. Median ranks and p-values consider all indicated studies simultaneously.
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Figure 2: AKR1B1 expression by gene fusion status in leukemia patients. AKR1B1 mRNA expression in leukemia patients with specific gene fusions and chromosomal rearrangements was compared to corresponding leukemia patients without the fusion across all leukemia types and for all such events where Oncomine contained multiple studies with such data. The heatmaps represent the relative expression in patients with the indicated fusions compared to those without, with red indicating over-expression in patients bearing the fusion and blue under-expression. Median ranks and p-values consider all indicated studies simultaneously.

Mentions: As shown in Figure 1, even for leukemia types in which AKRs are over-expressed compared to normal tissue at a high level of statistical significance, there is considerable heterogeneity amongst patients in terms of AKR1B1 and AKR1B10 expression (Figure 1A). This led us to ask whether AKR expression could identify certain types of patients within these leukemias, and we found that high levels of AKR1B1 expression within B-cell leukemia patients was strongly associated with the presence of the TCF3-PBX1 gene fusion (Figure 1B), while under-expression of AKR1B1 in chronic myelogenous leukemias was associated with the presence of the PML-RARA gene fusion (Figure 1C). Across all translocations and gene fusions in all leukemia types, AKR1B1 over-expression is associated with the TCF3-PBX1 gene fusion and 11q23 MLL rearrangements, while under-expression is associated with the PML-RARA and ETV6-RUNX1 gene fusions (Figure 2). Other gene fusions, translocations, and point mutations examined in leukemias did not have a statistically significant, consistent pattern (Figure 2 and data not shown).


Expression of the Aldo-Ketoreductases AKR1B1 and AKR1B10 in Human Cancers.

Laffin B, Petrash JM - Front Pharmacol (2012)

AKR1B1 expression by gene fusion status in leukemia patients. AKR1B1 mRNA expression in leukemia patients with specific gene fusions and chromosomal rearrangements was compared to corresponding leukemia patients without the fusion across all leukemia types and for all such events where Oncomine contained multiple studies with such data. The heatmaps represent the relative expression in patients with the indicated fusions compared to those without, with red indicating over-expression in patients bearing the fusion and blue under-expression. Median ranks and p-values consider all indicated studies simultaneously.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368246&req=5

Figure 2: AKR1B1 expression by gene fusion status in leukemia patients. AKR1B1 mRNA expression in leukemia patients with specific gene fusions and chromosomal rearrangements was compared to corresponding leukemia patients without the fusion across all leukemia types and for all such events where Oncomine contained multiple studies with such data. The heatmaps represent the relative expression in patients with the indicated fusions compared to those without, with red indicating over-expression in patients bearing the fusion and blue under-expression. Median ranks and p-values consider all indicated studies simultaneously.
Mentions: As shown in Figure 1, even for leukemia types in which AKRs are over-expressed compared to normal tissue at a high level of statistical significance, there is considerable heterogeneity amongst patients in terms of AKR1B1 and AKR1B10 expression (Figure 1A). This led us to ask whether AKR expression could identify certain types of patients within these leukemias, and we found that high levels of AKR1B1 expression within B-cell leukemia patients was strongly associated with the presence of the TCF3-PBX1 gene fusion (Figure 1B), while under-expression of AKR1B1 in chronic myelogenous leukemias was associated with the presence of the PML-RARA gene fusion (Figure 1C). Across all translocations and gene fusions in all leukemia types, AKR1B1 over-expression is associated with the TCF3-PBX1 gene fusion and 11q23 MLL rearrangements, while under-expression is associated with the PML-RARA and ETV6-RUNX1 gene fusions (Figure 2). Other gene fusions, translocations, and point mutations examined in leukemias did not have a statistically significant, consistent pattern (Figure 2 and data not shown).

Bottom Line: Using this database, we found that expression of AKR1B1 and AKR1B10 varies greatly by cancer type and tissue of origin, including agreement with previous reports that AKR1B10 is significantly over-expressed in cancers of the lungs and liver.AKR1B1 over-expression was found to be associated with shortened patient survival in acute myelogenous leukemias and multiple myelomas.High AKR1B10 expression tends to predict less aggressive clinical course generally, notably within lung cancers, where it tends to be highly over-expressed compared to normal tissue.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, The School of Medicine, University of Colorado Aurora, CO, USA.

ABSTRACT
The American Cancer Society estimates that there will be more than 1.5 million new cases of cancer in 2011, underscoring the need for identification of new therapeutic targets and development of novel cancer therapies. Previous studies have implicated the human aldo-ketoreductases AKR1B1 and AKR1B10 in cancer, and therefore we examined AKR1B1 and AKR1B10 expression across all major human cancer types using the Oncomine cancer gene expression database (Compendia Biosciences, www.oncomine.com). Using this database, we found that expression of AKR1B1 and AKR1B10 varies greatly by cancer type and tissue of origin, including agreement with previous reports that AKR1B10 is significantly over-expressed in cancers of the lungs and liver. AKR1B1 is more broadly over-expressed in human cancers than AKR1B10, albeit at a generally lower magnitude. AKR1B1 over-expression was found to be associated with shortened patient survival in acute myelogenous leukemias and multiple myelomas. High AKR1B10 expression tends to predict less aggressive clinical course generally, notably within lung cancers, where it tends to be highly over-expressed compared to normal tissue. These findings suggest that AKR1B1 inhibitors in particular hold great potential as novel cancer therapeutics.

No MeSH data available.


Related in: MedlinePlus