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Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL
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| Zeitschriftentitel: | Blood |
|---|---|
| Personen und Körperschaften: | , , , , , |
| In: | Blood, 107, 2006, 11, S. 4524-4531 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Hematology
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| Schlagwörter: |
| author_facet |
Meyer, Lüder Hinrich Karawajew, Leonid Schrappe, Martin Ludwig, Wolf-Dieter Debatin, Klaus-Michael Stahnke, Karsten Meyer, Lüder Hinrich Karawajew, Leonid Schrappe, Martin Ludwig, Wolf-Dieter Debatin, Klaus-Michael Stahnke, Karsten |
|---|---|
| author |
Meyer, Lüder Hinrich Karawajew, Leonid Schrappe, Martin Ludwig, Wolf-Dieter Debatin, Klaus-Michael Stahnke, Karsten |
| spellingShingle |
Meyer, Lüder Hinrich Karawajew, Leonid Schrappe, Martin Ludwig, Wolf-Dieter Debatin, Klaus-Michael Stahnke, Karsten Blood Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL Cell Biology Hematology Immunology Biochemistry |
| author_sort |
meyer, lüder hinrich |
| spelling |
Meyer, Lüder Hinrich Karawajew, Leonid Schrappe, Martin Ludwig, Wolf-Dieter Debatin, Klaus-Michael Stahnke, Karsten 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood-2005-08-3305 <jats:title>Abstract</jats:title><jats:p>Deficient activation of apoptosis signaling pathways may be responsible for treatment failure in acute leukemia. Here, we address the impact of intact apoptosis signaling in 78 patients with pediatric precursor B-cell acute lymphoblastic leukemia (ALL) by analysis of 2 key apoptogenic events: caspase-3 activation and cytochrome c release in leukemia cells cultured in vitro. Both events correlated only in the group of patients who had a good response and patients in continuous remission, suggesting that intact apoptosis signaling is a characteristic for favorable outcome. By combining both parameters, we identified a novel indicator, cytochrome c–related activation of caspase-3 (CRAC). CRAC directly connects the extent of caspase-3 activation to cytochrome c release in single cells in an individual patient sample. In CRAC-positive patients, indicating proficient apoptosis signaling, the number of persisting leukemia cells on day 15 was significantly lower than in the CRAC-negative patient group (n = 27, mean 6.0% versus n = 36, mean 22.6%; P = .003). At a median follow-up of 31 months, disease-free survival was 84 months (95% CI = 76 to 91 months) and 66 months (95% CI = 52 to 80 months) for patients with positive and negative CRAC, respectively (P = .019). CRAC may serve as a functionally defined risk factor for treatment stratification.</jats:p> Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL Blood |
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10.1182/blood-2005-08-3305 |
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American Society of Hematology, 2006 |
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American Society of Hematology, 2006 |
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| title |
Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL |
| title_unstemmed |
Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL |
| title_full |
Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL |
| title_fullStr |
Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL |
| title_full_unstemmed |
Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL |
| title_short |
Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL |
| title_sort |
cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor b-cell all |
| topic |
Cell Biology Hematology Immunology Biochemistry |
| url |
http://dx.doi.org/10.1182/blood-2005-08-3305 |
| publishDate |
2006 |
| physical |
4524-4531 |
| description |
<jats:title>Abstract</jats:title><jats:p>Deficient activation of apoptosis signaling pathways may be responsible for treatment failure in acute leukemia. Here, we address the impact of intact apoptosis signaling in 78 patients with pediatric precursor B-cell acute lymphoblastic leukemia (ALL) by analysis of 2 key apoptogenic events: caspase-3 activation and cytochrome c release in leukemia cells cultured in vitro. Both events correlated only in the group of patients who had a good response and patients in continuous remission, suggesting that intact apoptosis signaling is a characteristic for favorable outcome. By combining both parameters, we identified a novel indicator, cytochrome c–related activation of caspase-3 (CRAC). CRAC directly connects the extent of caspase-3 activation to cytochrome c release in single cells in an individual patient sample. In CRAC-positive patients, indicating proficient apoptosis signaling, the number of persisting leukemia cells on day 15 was significantly lower than in the CRAC-negative patient group (n = 27, mean 6.0% versus n = 36, mean 22.6%; P = .003). At a median follow-up of 31 months, disease-free survival was 84 months (95% CI = 76 to 91 months) and 66 months (95% CI = 52 to 80 months) for patients with positive and negative CRAC, respectively (P = .019). CRAC may serve as a functionally defined risk factor for treatment stratification.</jats:p> |
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| author | Meyer, Lüder Hinrich, Karawajew, Leonid, Schrappe, Martin, Ludwig, Wolf-Dieter, Debatin, Klaus-Michael, Stahnke, Karsten |
| author_facet | Meyer, Lüder Hinrich, Karawajew, Leonid, Schrappe, Martin, Ludwig, Wolf-Dieter, Debatin, Klaus-Michael, Stahnke, Karsten, Meyer, Lüder Hinrich, Karawajew, Leonid, Schrappe, Martin, Ludwig, Wolf-Dieter, Debatin, Klaus-Michael, Stahnke, Karsten |
| author_sort | meyer, lüder hinrich |
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| description | <jats:title>Abstract</jats:title><jats:p>Deficient activation of apoptosis signaling pathways may be responsible for treatment failure in acute leukemia. Here, we address the impact of intact apoptosis signaling in 78 patients with pediatric precursor B-cell acute lymphoblastic leukemia (ALL) by analysis of 2 key apoptogenic events: caspase-3 activation and cytochrome c release in leukemia cells cultured in vitro. Both events correlated only in the group of patients who had a good response and patients in continuous remission, suggesting that intact apoptosis signaling is a characteristic for favorable outcome. By combining both parameters, we identified a novel indicator, cytochrome c–related activation of caspase-3 (CRAC). CRAC directly connects the extent of caspase-3 activation to cytochrome c release in single cells in an individual patient sample. In CRAC-positive patients, indicating proficient apoptosis signaling, the number of persisting leukemia cells on day 15 was significantly lower than in the CRAC-negative patient group (n = 27, mean 6.0% versus n = 36, mean 22.6%; P = .003). At a median follow-up of 31 months, disease-free survival was 84 months (95% CI = 76 to 91 months) and 66 months (95% CI = 52 to 80 months) for patients with positive and negative CRAC, respectively (P = .019). CRAC may serve as a functionally defined risk factor for treatment stratification.</jats:p> |
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| imprint | American Society of Hematology, 2006 |
| imprint_str_mv | American Society of Hematology, 2006 |
| institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Rs1, DE-Pl11, DE-105, DE-14, DE-Ch1, DE-L229 |
| issn | 0006-4971, 1528-0020 |
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| language | English |
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| spelling | Meyer, Lüder Hinrich Karawajew, Leonid Schrappe, Martin Ludwig, Wolf-Dieter Debatin, Klaus-Michael Stahnke, Karsten 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood-2005-08-3305 <jats:title>Abstract</jats:title><jats:p>Deficient activation of apoptosis signaling pathways may be responsible for treatment failure in acute leukemia. Here, we address the impact of intact apoptosis signaling in 78 patients with pediatric precursor B-cell acute lymphoblastic leukemia (ALL) by analysis of 2 key apoptogenic events: caspase-3 activation and cytochrome c release in leukemia cells cultured in vitro. Both events correlated only in the group of patients who had a good response and patients in continuous remission, suggesting that intact apoptosis signaling is a characteristic for favorable outcome. By combining both parameters, we identified a novel indicator, cytochrome c–related activation of caspase-3 (CRAC). CRAC directly connects the extent of caspase-3 activation to cytochrome c release in single cells in an individual patient sample. In CRAC-positive patients, indicating proficient apoptosis signaling, the number of persisting leukemia cells on day 15 was significantly lower than in the CRAC-negative patient group (n = 27, mean 6.0% versus n = 36, mean 22.6%; P = .003). At a median follow-up of 31 months, disease-free survival was 84 months (95% CI = 76 to 91 months) and 66 months (95% CI = 52 to 80 months) for patients with positive and negative CRAC, respectively (P = .019). CRAC may serve as a functionally defined risk factor for treatment stratification.</jats:p> Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL Blood |
| spellingShingle | Meyer, Lüder Hinrich, Karawajew, Leonid, Schrappe, Martin, Ludwig, Wolf-Dieter, Debatin, Klaus-Michael, Stahnke, Karsten, Blood, Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL, Cell Biology, Hematology, Immunology, Biochemistry |
| title | Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL |
| title_full | Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL |
| title_fullStr | Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL |
| title_full_unstemmed | Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL |
| title_short | Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL |
| title_sort | cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor b-cell all |
| title_unstemmed | Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL |
| topic | Cell Biology, Hematology, Immunology, Biochemistry |
| url | http://dx.doi.org/10.1182/blood-2005-08-3305 |