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

Hanfstein B, Lauseker M, Hehlmann R, Saussele S, Erben P, Dietz C, Fabarius A, Proetel U, Schnittger S, Haferlach C, Krause S, Schubert J, Einsele H, Haenel M, Dengler J, Falge C, Kanz L, Neubauer A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Spiekermann K, Baerlocher GM, Pfirrmann M, Hasford J, Hofmann WK, Hochhaus A, Mueller MC (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Haematologica Ferrata Storti Foundation

Publisher: Ferrata Storti Foundation

Book Volume: 99

Pages Range: 1441-7

Journal Issue: 9

DOI: 10.3324/haematol.2013.096537

Abstract

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 Euro risk score were observed. A significant difference was found between e13a2 and e14a2 when comparing white blood cells (88 vs. 65 × 10(9)/L, respectively; P<0.001) and platelets (296 vs. 430 × 10(9)/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).

Authors with CRIS profile

Stefan Krause Department of Medicine 5 – Haematology and Oncology

Involved external institutions

Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Universitätsklinikum Mannheim DE Germany (DE) Evangelisches Krankenhaus Hamm DE Germany (DE) Universitätsklinikum Würzburg DE Germany (DE) Klinikum Chemnitz DE Germany (DE) Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Klinikum Nürnberg DE Germany (DE) Universitätsklinikum Tübingen DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Universitätsklinikum Gießen und Marburg (UKGM) DE Germany (DE) MLL Münchner Leukämielabor GmbH DE Germany (DE) Friedrich-Schiller-Universität Jena DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE) Universitätsklinikum des Saarlandes (UKS) DE Germany (DE) Universitätsklinikum Freiburg DE Germany (DE)

How to cite

APA:

Hanfstein, B., Lauseker, M., Hehlmann, R., Saussele, S., Erben, P., Dietz, C.,... Mueller, M.C. (2014). Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib. Haematologica, 99(9), 1441-7. https://dx.doi.org/10.3324/haematol.2013.096537

MLA:

Hanfstein, Benjamin, et al. "Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib." Haematologica 99.9 (2014): 1441-7.

BibTeX: Download