Altered glucose metabolism in childhood pre-B acute lymphoblastic leukaemia
The cells of solid tumours are known to have an altered metabolism, with high rates of glucose uptake and glycolysis, which results in the excessive production of lactate. To date there has been no definitive research documenting metabolic changes in acute lymphoblastic leukaemia (ALL) cells. In ord...
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| Veröffentlicht in: | Leukemia 2006-10, Vol.20 (10), p.1731-1737 |
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| creator | BOAG, J. M BEESLEY, A. H FIRTH, M. J FREITAS, J. R FORD, J HOFFMANN, K CUMMINGS, A. J DE KLERK, N. H KEES, U. R |
| description | The cells of solid tumours are known to have an altered metabolism, with high rates of glucose uptake and glycolysis, which results in the excessive production of lactate. To date there has been no definitive research documenting metabolic changes in acute lymphoblastic leukaemia (ALL) cells. In order to investigate whether ALL cells have an altered metabolism, we initially compared the transcriptional profiles of 22 specimens from paediatric patients diagnosed with ALL to five CD34+ specimens isolated from bone marrow, which was verified in an independent cohort of 101 specimens. Profiling revealed the upregulation of genes facilitating glycolysis in the ALL specimens compared to the CD34+ specimens, while those involved in the tricarboxylic acid cycle were downregulated. Functional studies supported the microarray findings threefold: (1) higher expression of the glucose transport protein glucose transporter 1 in ALL compared to CD34+ specimens, (2) the excessive production of lactate in ALL cell lines and (3) sensitivity of ALL cell lines to the glycolysis inhibitor 2-deoxy-D-glucose. While metabolic alterations have been well documented in solid tumours, this is the first study to provide direct evidence for the existence of metabolic changes in the leukaemic cells of ALL patients. The finding offers new options for targeted therapy for ALL patients. |
| doi_str_mv | 10.1038/sj.leu.2404365 |
| format | Article |
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M ; BEESLEY, A. H ; FIRTH, M. J ; FREITAS, J. R ; FORD, J ; HOFFMANN, K ; CUMMINGS, A. J ; DE KLERK, N. H ; KEES, U. R</creator><creatorcontrib>BOAG, J. M ; BEESLEY, A. H ; FIRTH, M. J ; FREITAS, J. R ; FORD, J ; HOFFMANN, K ; CUMMINGS, A. J ; DE KLERK, N. H ; KEES, U. R</creatorcontrib><description>The cells of solid tumours are known to have an altered metabolism, with high rates of glucose uptake and glycolysis, which results in the excessive production of lactate. To date there has been no definitive research documenting metabolic changes in acute lymphoblastic leukaemia (ALL) cells. In order to investigate whether ALL cells have an altered metabolism, we initially compared the transcriptional profiles of 22 specimens from paediatric patients diagnosed with ALL to five CD34+ specimens isolated from bone marrow, which was verified in an independent cohort of 101 specimens. Profiling revealed the upregulation of genes facilitating glycolysis in the ALL specimens compared to the CD34+ specimens, while those involved in the tricarboxylic acid cycle were downregulated. Functional studies supported the microarray findings threefold: (1) higher expression of the glucose transport protein glucose transporter 1 in ALL compared to CD34+ specimens, (2) the excessive production of lactate in ALL cell lines and (3) sensitivity of ALL cell lines to the glycolysis inhibitor 2-deoxy-D-glucose. While metabolic alterations have been well documented in solid tumours, this is the first study to provide direct evidence for the existence of metabolic changes in the leukaemic cells of ALL patients. The finding offers new options for targeted therapy for ALL patients.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/sj.leu.2404365</identifier><identifier>PMID: 17041637</identifier><identifier>CODEN: LEUKED</identifier><language>eng</language><publisher>London: Nature Publishing</publisher><subject>Acute lymphoblastic leukemia ; Antigens, CD34 - metabolism ; B-Lymphocytes - metabolism ; B-Lymphocytes - pathology ; Biological and medical sciences ; Bone marrow ; Cancer research ; CD34 antigen ; Cell Line, Tumor ; Cell lines ; Child ; Childhood ; Children ; Childrens health ; Citric Acid Cycle - genetics ; Deoxyglucose - pharmacokinetics ; DNA microarrays ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation, Leukemic ; Glucose ; Glucose - pharmacokinetics ; Glucose metabolism ; Glucose transport ; Glucose transporter ; Glucose Transporter Type 1 - genetics ; Glucose Transporter Type 1 - metabolism ; Glycolysis ; Glycolysis - genetics ; Hematologic and hematopoietic diseases ; Humans ; Lactic acid ; Lactic Acid - metabolism ; Leukemia ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Medical research ; Medical sciences ; Metabolism ; Patients ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - physiopathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - physiopathology ; Protein transport ; Quality control ; RNA, Messenger - metabolism ; Solid tumors ; Transcription ; Tricarboxylic acid cycle ; Tumors ; Up-Regulation</subject><ispartof>Leukemia, 2006-10, Vol.20 (10), p.1731-1737</ispartof><rights>2007 INIST-CNRS</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Oct 2006</rights><rights>Nature Publishing Group 2006.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c530t-23a9e8254253fac624ee0077a118cc0a04df933cf650b49dc78153c9654bab463</citedby><cites>FETCH-LOGICAL-c530t-23a9e8254253fac624ee0077a118cc0a04df933cf650b49dc78153c9654bab463</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2727,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18155368$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17041637$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BOAG, J. M</creatorcontrib><creatorcontrib>BEESLEY, A. H</creatorcontrib><creatorcontrib>FIRTH, M. J</creatorcontrib><creatorcontrib>FREITAS, J. R</creatorcontrib><creatorcontrib>FORD, J</creatorcontrib><creatorcontrib>HOFFMANN, K</creatorcontrib><creatorcontrib>CUMMINGS, A. J</creatorcontrib><creatorcontrib>DE KLERK, N. H</creatorcontrib><creatorcontrib>KEES, U. R</creatorcontrib><title>Altered glucose metabolism in childhood pre-B acute lymphoblastic leukaemia</title><title>Leukemia</title><addtitle>Leukemia</addtitle><description>The cells of solid tumours are known to have an altered metabolism, with high rates of glucose uptake and glycolysis, which results in the excessive production of lactate. To date there has been no definitive research documenting metabolic changes in acute lymphoblastic leukaemia (ALL) cells. In order to investigate whether ALL cells have an altered metabolism, we initially compared the transcriptional profiles of 22 specimens from paediatric patients diagnosed with ALL to five CD34+ specimens isolated from bone marrow, which was verified in an independent cohort of 101 specimens. Profiling revealed the upregulation of genes facilitating glycolysis in the ALL specimens compared to the CD34+ specimens, while those involved in the tricarboxylic acid cycle were downregulated. Functional studies supported the microarray findings threefold: (1) higher expression of the glucose transport protein glucose transporter 1 in ALL compared to CD34+ specimens, (2) the excessive production of lactate in ALL cell lines and (3) sensitivity of ALL cell lines to the glycolysis inhibitor 2-deoxy-D-glucose. While metabolic alterations have been well documented in solid tumours, this is the first study to provide direct evidence for the existence of metabolic changes in the leukaemic cells of ALL patients. The finding offers new options for targeted therapy for ALL patients.</description><subject>Acute lymphoblastic leukemia</subject><subject>Antigens, CD34 - metabolism</subject><subject>B-Lymphocytes - metabolism</subject><subject>B-Lymphocytes - pathology</subject><subject>Biological and medical sciences</subject><subject>Bone marrow</subject><subject>Cancer research</subject><subject>CD34 antigen</subject><subject>Cell Line, Tumor</subject><subject>Cell lines</subject><subject>Child</subject><subject>Childhood</subject><subject>Children</subject><subject>Childrens health</subject><subject>Citric Acid Cycle - genetics</subject><subject>Deoxyglucose - pharmacokinetics</subject><subject>DNA microarrays</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Leukemic</subject><subject>Glucose</subject><subject>Glucose - pharmacokinetics</subject><subject>Glucose metabolism</subject><subject>Glucose transport</subject><subject>Glucose transporter</subject><subject>Glucose Transporter Type 1 - genetics</subject><subject>Glucose Transporter Type 1 - metabolism</subject><subject>Glycolysis</subject><subject>Glycolysis - genetics</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Lactic acid</subject><subject>Lactic Acid - metabolism</subject><subject>Leukemia</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Metabolism</subject><subject>Patients</subject><subject>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics</subject><subject>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism</subject><subject>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - physiopathology</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - physiopathology</subject><subject>Protein transport</subject><subject>Quality control</subject><subject>RNA, Messenger - metabolism</subject><subject>Solid tumors</subject><subject>Transcription</subject><subject>Tricarboxylic acid cycle</subject><subject>Tumors</subject><subject>Up-Regulation</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp90ktv1DAQAOAIgehSuHIDRaCWUxa_7RyXqjxEJS5wthxn0vXixFvbOfTf41UDC6ggHyzZ38xo7Kmq5xitMaLqbdqtPcxrwhCjgj-oVphJ0XDO8cNqhZSSjWgJO6mepLRD6HApHlcnWCKGBZWr6vPGZ4jQ19d-tiFBPUI2XfAujbWbart1vt-G0Nf7CM272tg5Q-1vx_02dN6k7Gxd6n83MDrztHo0GJ_g2bKfVt_eX369-Nhcffnw6WJz1VhOUW4INS0owhnhdDBWEAaAkJQGY2UtMoj1Q0upHQRHHWt7KxXm1LaCs850TNDT6s1d3n0MNzOkrEeXLHhvJghz0gpLgUgrDvL8v1KolreckwJf_wV3YY5T6UITwbhEraSsqFf_VASVhqTkx1TXxoN20xByNPZQV2-wUuUJSidFre9RZfXlJW2YYHDl_I-A898CtmB83qbg5-zClO7NbGNIKcKg99GNJt5qjPRhZnTa6fJnepmZEvBy6WruRuiPfBmSAs4WYJI1fohmsi4dXfkeToUq7sWdm0yeI_wCPwv9AIkbz3c</recordid><startdate>20061001</startdate><enddate>20061001</enddate><creator>BOAG, J. 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M ; BEESLEY, A. H ; FIRTH, M. J ; FREITAS, J. R ; FORD, J ; HOFFMANN, K ; CUMMINGS, A. J ; DE KLERK, N. H ; KEES, U. 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M</au><au>BEESLEY, A. H</au><au>FIRTH, M. J</au><au>FREITAS, J. R</au><au>FORD, J</au><au>HOFFMANN, K</au><au>CUMMINGS, A. J</au><au>DE KLERK, N. H</au><au>KEES, U. R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered glucose metabolism in childhood pre-B acute lymphoblastic leukaemia</atitle><jtitle>Leukemia</jtitle><addtitle>Leukemia</addtitle><date>2006-10-01</date><risdate>2006</risdate><volume>20</volume><issue>10</issue><spage>1731</spage><epage>1737</epage><pages>1731-1737</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><coden>LEUKED</coden><abstract>The cells of solid tumours are known to have an altered metabolism, with high rates of glucose uptake and glycolysis, which results in the excessive production of lactate. To date there has been no definitive research documenting metabolic changes in acute lymphoblastic leukaemia (ALL) cells. In order to investigate whether ALL cells have an altered metabolism, we initially compared the transcriptional profiles of 22 specimens from paediatric patients diagnosed with ALL to five CD34+ specimens isolated from bone marrow, which was verified in an independent cohort of 101 specimens. Profiling revealed the upregulation of genes facilitating glycolysis in the ALL specimens compared to the CD34+ specimens, while those involved in the tricarboxylic acid cycle were downregulated. Functional studies supported the microarray findings threefold: (1) higher expression of the glucose transport protein glucose transporter 1 in ALL compared to CD34+ specimens, (2) the excessive production of lactate in ALL cell lines and (3) sensitivity of ALL cell lines to the glycolysis inhibitor 2-deoxy-D-glucose. While metabolic alterations have been well documented in solid tumours, this is the first study to provide direct evidence for the existence of metabolic changes in the leukaemic cells of ALL patients. The finding offers new options for targeted therapy for ALL patients.</abstract><cop>London</cop><pub>Nature Publishing</pub><pmid>17041637</pmid><doi>10.1038/sj.leu.2404365</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Leukemia, 2006-10, Vol.20 (10), p.1731-1737 |
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| source | MEDLINE; Nature; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Acute lymphoblastic leukemia Antigens, CD34 - metabolism B-Lymphocytes - metabolism B-Lymphocytes - pathology Biological and medical sciences Bone marrow Cancer research CD34 antigen Cell Line, Tumor Cell lines Child Childhood Children Childrens health Citric Acid Cycle - genetics Deoxyglucose - pharmacokinetics DNA microarrays Gene expression Gene Expression Profiling Gene Expression Regulation, Leukemic Glucose Glucose - pharmacokinetics Glucose metabolism Glucose transport Glucose transporter Glucose Transporter Type 1 - genetics Glucose Transporter Type 1 - metabolism Glycolysis Glycolysis - genetics Hematologic and hematopoietic diseases Humans Lactic acid Lactic Acid - metabolism Leukemia Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Medical research Medical sciences Metabolism Patients Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - physiopathology Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism Precursor Cell Lymphoblastic Leukemia-Lymphoma - physiopathology Protein transport Quality control RNA, Messenger - metabolism Solid tumors Transcription Tricarboxylic acid cycle Tumors Up-Regulation |
| title | Altered glucose metabolism in childhood pre-B acute lymphoblastic leukaemia |
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