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Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib

Please always quote using this URN: urn:nbn:de:bvb:20-opus-115476
  • The vast majority of chronic myeloid leukemia patients express a BCR-ABL1 fusion gene mRNA encoding a 210 kDa tyrosine kinase which promotes leukemic transformation. A possible differential impact of the corresponding BCR-ABL1 transcript variants e13a2 ("b2a2") and e14a2 ("b3a2") on disease phenotype and outcome is still a subject of debate. A total of 1105 newly diagnosed imatinib-treated patients were analyzed according to transcript type at diagnosis (e13a2, n=451; e14a2, n=496; e13a2+e14a2, n=158). No differences regarding age, sex, or EuroThe vast majority of chronic myeloid leukemia patients express a BCR-ABL1 fusion gene mRNA encoding a 210 kDa tyrosine kinase which promotes leukemic transformation. A possible differential impact of the corresponding BCR-ABL1 transcript variants e13a2 ("b2a2") and e14a2 ("b3a2") on disease phenotype and outcome is still a subject of debate. A total of 1105 newly diagnosed imatinib-treated patients were analyzed according to transcript type at diagnosis (e13a2, n=451; e14a2, n=496; e13a2+e14a2, n=158). No differences regarding age, sex, or Euro risk score were observed. A significant difference was found between e13a2 and e14a2 when comparing white blood cells (88 vs. 65 x 10(9)/L, respectively; P<0.001) and platelets (296 vs. 430 x 109/L, respectively; P<0.001) at diagnosis, indicating a distinct disease phenotype. No significant difference was observed regarding other hematologic features, including spleen size and hematologic adverse events, during imatinib-based therapies. Cumulative molecular response was inferior in e13a2 patients (P=0.002 for major molecular response; P<0.001 for MR4). No difference was observed with regard to cytogenetic response and overall survival. In conclusion, e13a2 and e14a2 chronic myeloid leukemia seem to represent distinct biological entities. However, clinical outcome under imatinib treatment was comparable and no risk prediction can be made according to e13a2 versus e14a2 BCR-ABL1 transcript type at diagnosis. (clinicaltrials.gov identifier: 00055874)show moreshow less

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Metadaten
Author: Benjamin Hanfstein, Michael Lauseker, Rüdiger Hehlmann, Susanne Saussele, Philipp Erben, Christian Dietz, Alice Fabarius, Ulrike Proetel, Susanne Schnittger, Claudia Haferlach, Stefan W. Krause, Jörg Schubert, Hermann Einsele, Mathias Hänel, Jolanta Dengler, Christiane Falge, Lothar Kanz, Andreas Neubauer, Michael Kneba, Frank Stengelmann, Michael Pfreundschuh, Cornelius F. Waller, Karsten Spiekerman, Gabriela M. Baerlocher, Markus Pfirrmann, Joerg Hasford, Wolf-Karsten Hofmann, Andreas Hochhaus, Martin C. Müller
URN:urn:nbn:de:bvb:20-opus-115476
Document Type:Journal article
Faculties:Medizinische Fakultät / Medizinische Klinik und Poliklinik II
Language:English
Parent Title (English):Haematologica
ISSN:1592-8721
Year of Completion:2014
Volume:99
Issue:9
Pagenumber:1441-1447
Source:Haematologica 2014 99(9) 1441-1447. DOI 10.3324/haematol.2013.096537
DOI:https://doi.org/10.3324/haematol.2013.096537
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/24837466
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:ABL gene; breakpoint; chronic myelogenous leukemia; chronic phase; cytogenetic response; hybrid messenger RNA; no correlation; polymerase-chain-reaktion; survival; transcripts
Release Date:2015/07/14
Licence (German):License LogoDeutsches Urheberrecht