Effect of the Philadelphia chromosome on minimal residual disease in acute lymphoblastic leukemia
The Philadelphia translocation is associated with a poor prognosis in adults and children with acute lymphoblastic leukemia, even though the majority of patients achieve remission. To test the hypothesis that the translocation leads to drug resistance in vivo, we studied 61 children and 20 adults wi...
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| Veröffentlicht in: | Leukemia 1997-09, Vol.11 (9), p.1497-1500 |
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| creator | BRISCO, M. J SYKES, P. J MORLEY, A. A DOLMAN, G NEOH, S.-H HUGHES, E PENG, L.-M TAURO, G EKERT, H TOOGOOD, I BRADSTOCK, K |
| description | The Philadelphia translocation is associated with a poor prognosis in adults and children with acute lymphoblastic leukemia, even though the majority of patients achieve remission. To test the hypothesis that the translocation leads to drug resistance in vivo, we studied 61 children and 20 adults with acute lymphoblastic leukemia and used the level of minimal residual disease at the end of induction as the measure of drug resistance in vivo. In children the presence of the translocation was associated with a significant increase in residual disease, indicating higher drug resistance in vivo; five of seven Philadelphia-positive children but only five of 54 Philadelphia-negative children had a minimal residual disease level >10(-3), a level which is associated with a high risk of relapse in childhood acute lymphoblastic leukemia of standard risk. By contrast, in adults, residual disease and hence drug resistance was already higher than in children, and the presence of the Philadelphia translocation in seven patients had no obvious additional effect. We conclude that the Philadelphia chromosome may increase resistance to drugs in vivo in children, but not detectably in adults. |
| doi_str_mv | 10.1038/sj.leu.2400759 |
| format | Article |
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J ; SYKES, P. J ; MORLEY, A. A ; DOLMAN, G ; NEOH, S.-H ; HUGHES, E ; PENG, L.-M ; TAURO, G ; EKERT, H ; TOOGOOD, I ; BRADSTOCK, K</creator><creatorcontrib>BRISCO, M. J ; SYKES, P. J ; MORLEY, A. A ; DOLMAN, G ; NEOH, S.-H ; HUGHES, E ; PENG, L.-M ; TAURO, G ; EKERT, H ; TOOGOOD, I ; BRADSTOCK, K</creatorcontrib><description>The Philadelphia translocation is associated with a poor prognosis in adults and children with acute lymphoblastic leukemia, even though the majority of patients achieve remission. To test the hypothesis that the translocation leads to drug resistance in vivo, we studied 61 children and 20 adults with acute lymphoblastic leukemia and used the level of minimal residual disease at the end of induction as the measure of drug resistance in vivo. In children the presence of the translocation was associated with a significant increase in residual disease, indicating higher drug resistance in vivo; five of seven Philadelphia-positive children but only five of 54 Philadelphia-negative children had a minimal residual disease level >10(-3), a level which is associated with a high risk of relapse in childhood acute lymphoblastic leukemia of standard risk. By contrast, in adults, residual disease and hence drug resistance was already higher than in children, and the presence of the Philadelphia translocation in seven patients had no obvious additional effect. We conclude that the Philadelphia chromosome may increase resistance to drugs in vivo in children, but not detectably in adults.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/sj.leu.2400759</identifier><identifier>PMID: 9305604</identifier><identifier>CODEN: LEUKED</identifier><language>eng</language><publisher>London: Nature Publishing</publisher><subject>Acute lymphoblastic leukemia ; Adolescent ; Adult ; Adults ; Aged ; Antineoplastic agents ; Biological and medical sciences ; Chemotherapy ; Child ; Child, Preschool ; Children ; Chromosome Aberrations - diagnosis ; Chromosome Disorders ; Chromosomes ; Disease resistance ; Drug resistance ; Female ; Fusion Proteins, bcr-abl - genetics ; Humans ; In vivo methods and tests ; Infant ; Leukemia ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology ; Lymphatic leukemia ; Male ; Medical sciences ; Minimal residual disease ; Pharmacology. 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J</creatorcontrib><creatorcontrib>SYKES, P. J</creatorcontrib><creatorcontrib>MORLEY, A. A</creatorcontrib><creatorcontrib>DOLMAN, G</creatorcontrib><creatorcontrib>NEOH, S.-H</creatorcontrib><creatorcontrib>HUGHES, E</creatorcontrib><creatorcontrib>PENG, L.-M</creatorcontrib><creatorcontrib>TAURO, G</creatorcontrib><creatorcontrib>EKERT, H</creatorcontrib><creatorcontrib>TOOGOOD, I</creatorcontrib><creatorcontrib>BRADSTOCK, K</creatorcontrib><title>Effect of the Philadelphia chromosome on minimal residual disease in acute lymphoblastic leukemia</title><title>Leukemia</title><addtitle>Leukemia</addtitle><description>The Philadelphia translocation is associated with a poor prognosis in adults and children with acute lymphoblastic leukemia, even though the majority of patients achieve remission. To test the hypothesis that the translocation leads to drug resistance in vivo, we studied 61 children and 20 adults with acute lymphoblastic leukemia and used the level of minimal residual disease at the end of induction as the measure of drug resistance in vivo. In children the presence of the translocation was associated with a significant increase in residual disease, indicating higher drug resistance in vivo; five of seven Philadelphia-positive children but only five of 54 Philadelphia-negative children had a minimal residual disease level >10(-3), a level which is associated with a high risk of relapse in childhood acute lymphoblastic leukemia of standard risk. By contrast, in adults, residual disease and hence drug resistance was already higher than in children, and the presence of the Philadelphia translocation in seven patients had no obvious additional effect. We conclude that the Philadelphia chromosome may increase resistance to drugs in vivo in children, but not detectably in adults.</description><subject>Acute lymphoblastic leukemia</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Adults</subject><subject>Aged</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Chemotherapy</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Chromosome Aberrations - diagnosis</subject><subject>Chromosome Disorders</subject><subject>Chromosomes</subject><subject>Disease resistance</subject><subject>Drug resistance</subject><subject>Female</subject><subject>Fusion Proteins, bcr-abl - genetics</subject><subject>Humans</subject><subject>In vivo methods and tests</subject><subject>Infant</subject><subject>Leukemia</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology</subject><subject>Lymphatic leukemia</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Minimal residual disease</subject><subject>Pharmacology. Drug treatments</subject><subject>Philadelphia chromosome</subject><subject>Polymerase Chain Reaction</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology</subject><subject>Prognosis</subject><subject>Remission</subject><subject>Translocation</subject><subject>Translocation, Genetic</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9v1TAMxyMEGm-DKzekSCBufTg_mqZHNA2GNAkOcI7S1FHzSJtH0h723y_Tqh24cLLl78eW7S8h7xgcGQj9uZyOEbcjlwBd278gByY71bRty16SA2jdNarn8jW5LOUE8CiqC3LRC2gVyAOxN96jW2nydJ2Q_pxCtCPG8xQsdVNOcyppRpoWOoclzDbSjCWMW03GUNAWpGGh1m0r0ng_n6c0RFvW4Gjd6g_Owb4hr7yNBd_u8Yr8_nrz6_q2ufvx7fv1l7vGSQ5r03NA5aUSo-i5B9n3gKLlig9MuVrCgQulYRyVGBhTmkmmBj9qywbmx8pekU9Pc885_d2wrGYOxWGMdsG0FdPVm5kA8V-QKcmE6LoKfvgHPKUtL_UIw5Vsle5bUJU6PlEup1IyenPO9VH53jAwjxaZcjL1GWa3qDa838duw4zjM757UvWPu26Ls9Fnu7hQnjGugWkhxAPAfJk3</recordid><startdate>19970901</startdate><enddate>19970901</enddate><creator>BRISCO, M. 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| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Acute lymphoblastic leukemia Adolescent Adult Adults Aged Antineoplastic agents Biological and medical sciences Chemotherapy Child Child, Preschool Children Chromosome Aberrations - diagnosis Chromosome Disorders Chromosomes Disease resistance Drug resistance Female Fusion Proteins, bcr-abl - genetics Humans In vivo methods and tests Infant Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology Lymphatic leukemia Male Medical sciences Minimal residual disease Pharmacology. Drug treatments Philadelphia chromosome Polymerase Chain Reaction Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology Prognosis Remission Translocation Translocation, Genetic |
| title | Effect of the Philadelphia chromosome on minimal residual disease in acute lymphoblastic leukemia |
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