Molecular Diagnostics, Targeted Therapy, and the Indication for Allogeneic Stem Cell Transplantation in Acute Lymphoblastic Leukemia
In recent years, the panel of known molecular mutations in acute lymphoblastic leukemia (ALL) has been continuously increased. In Philadelphia-positive ALL, deletions of the IKZF1 gene were identified as prognostically adverse factors. These improved insights in the molecular background and the clin...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Advances in Hematology |
| Online Access: | http://dx.doi.org/10.1155/2011/154745 |
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| author | Anthony Oyekunle Torsten Haferlach Nicolaus Kröger Evgeny Klyuchnikov Axel Rolf Zander Susanne Schnittger Ulrike Bacher |
| author_facet | Anthony Oyekunle Torsten Haferlach Nicolaus Kröger Evgeny Klyuchnikov Axel Rolf Zander Susanne Schnittger Ulrike Bacher |
| author_sort | Anthony Oyekunle |
| collection | DOAJ |
| description | In recent years, the panel of known molecular mutations in acute lymphoblastic leukemia (ALL) has been continuously increased. In Philadelphia-positive ALL, deletions of the IKZF1 gene were identified as prognostically adverse factors. These improved insights in the molecular background and the clinical heterogeneity of distinct cytogenetic subgroups may allow most differentiated therapeutic decisions, for example, with respect to the indication to allogeneic HSCT within genetically defined ALL subtypes. Quantitative real-time PCR allows highly sensitive monitoring of the minimal residual disease (MRD) load, either based on reciprocal gene fusions or immune gene rearrangements. Molecular diagnostics provided the basis for targeted therapy concepts, for example, combining the tyrosine kinase inhibitor imatinib with chemotherapy in patients with Philadelphia-positive ALL. Screening for BCR-ABL1 mutations in Philadelphia-positive ALL allows to identify patients who may benefit from second-generation tyrosine kinase inhibitors or from novel compounds targeting the T315I mutation. Considering the central role of the molecular techniques for the management of patients with ALL, efforts should be made to facilitate and harmonize immunophenotyping, cytogenetics, and molecular mutation screening. Furthermore, the potential of high-throughput sequencing should be evaluated for diagnosis and follow-up of patients with B-lineage ALL. |
| format | Article |
| id | doaj-art-594b0e5b1ed9442fb8f916c853d13dc3 |
| institution | OA Journals |
| issn | 1687-9104 1687-9112 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advances in Hematology |
| spelling | doaj-art-594b0e5b1ed9442fb8f916c853d13dc32025-08-20T02:05:33ZengWileyAdvances in Hematology1687-91041687-91122011-01-01201110.1155/2011/154745154745Molecular Diagnostics, Targeted Therapy, and the Indication for Allogeneic Stem Cell Transplantation in Acute Lymphoblastic LeukemiaAnthony Oyekunle0Torsten Haferlach1Nicolaus Kröger2Evgeny Klyuchnikov3Axel Rolf Zander4Susanne Schnittger5Ulrike Bacher6Department for Stem Cell Transplantation, University Cancer Center Hamburg (UCCH), 20246 Hamburg, GermanyMLL Munich Leukemia Laboratory, Munich, GermanyDepartment for Stem Cell Transplantation, University Cancer Center Hamburg (UCCH), 20246 Hamburg, GermanyDepartment for Stem Cell Transplantation, University Cancer Center Hamburg (UCCH), 20246 Hamburg, GermanyDepartment for Stem Cell Transplantation, University Cancer Center Hamburg (UCCH), 20246 Hamburg, GermanyMLL Munich Leukemia Laboratory, Munich, GermanyDepartment for Stem Cell Transplantation, University Cancer Center Hamburg (UCCH), 20246 Hamburg, GermanyIn recent years, the panel of known molecular mutations in acute lymphoblastic leukemia (ALL) has been continuously increased. In Philadelphia-positive ALL, deletions of the IKZF1 gene were identified as prognostically adverse factors. These improved insights in the molecular background and the clinical heterogeneity of distinct cytogenetic subgroups may allow most differentiated therapeutic decisions, for example, with respect to the indication to allogeneic HSCT within genetically defined ALL subtypes. Quantitative real-time PCR allows highly sensitive monitoring of the minimal residual disease (MRD) load, either based on reciprocal gene fusions or immune gene rearrangements. Molecular diagnostics provided the basis for targeted therapy concepts, for example, combining the tyrosine kinase inhibitor imatinib with chemotherapy in patients with Philadelphia-positive ALL. Screening for BCR-ABL1 mutations in Philadelphia-positive ALL allows to identify patients who may benefit from second-generation tyrosine kinase inhibitors or from novel compounds targeting the T315I mutation. Considering the central role of the molecular techniques for the management of patients with ALL, efforts should be made to facilitate and harmonize immunophenotyping, cytogenetics, and molecular mutation screening. Furthermore, the potential of high-throughput sequencing should be evaluated for diagnosis and follow-up of patients with B-lineage ALL.http://dx.doi.org/10.1155/2011/154745 |
| spellingShingle | Anthony Oyekunle Torsten Haferlach Nicolaus Kröger Evgeny Klyuchnikov Axel Rolf Zander Susanne Schnittger Ulrike Bacher Molecular Diagnostics, Targeted Therapy, and the Indication for Allogeneic Stem Cell Transplantation in Acute Lymphoblastic Leukemia Advances in Hematology |
| title | Molecular Diagnostics, Targeted Therapy, and the Indication for Allogeneic Stem Cell Transplantation in Acute Lymphoblastic Leukemia |
| title_full | Molecular Diagnostics, Targeted Therapy, and the Indication for Allogeneic Stem Cell Transplantation in Acute Lymphoblastic Leukemia |
| title_fullStr | Molecular Diagnostics, Targeted Therapy, and the Indication for Allogeneic Stem Cell Transplantation in Acute Lymphoblastic Leukemia |
| title_full_unstemmed | Molecular Diagnostics, Targeted Therapy, and the Indication for Allogeneic Stem Cell Transplantation in Acute Lymphoblastic Leukemia |
| title_short | Molecular Diagnostics, Targeted Therapy, and the Indication for Allogeneic Stem Cell Transplantation in Acute Lymphoblastic Leukemia |
| title_sort | molecular diagnostics targeted therapy and the indication for allogeneic stem cell transplantation in acute lymphoblastic leukemia |
| url | http://dx.doi.org/10.1155/2011/154745 |
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