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

Hanfstein, Benjamin; Lauseker, Michael; Hehlmann, Rüdiger; Saussele, Susanne; Erben, Philipp; Dietz, Christian; Fabarius, Alice; Proetel, Ulrike; Schnittger, Susanne; Haferlach, Claudia; Krause, Stefan W; Schubert, Jörg; Einsele, Hermann; Hänel, Mathias; Dengler, Jolanta; Falge, Christiane; Kanz, Lothar; Neubauer, Andreas; Kneba, Michael; Stegelmann, Frank; ... (2014). Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib. Haematologica - the hematology journal, 99(9), pp. 1441-1447. Ferrata-Storti Foundation 10.3324/haematol.2013.096537

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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).

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory

UniBE Contributor:

Baerlocher, Gabriela M.

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0390-6078

Publisher:

Ferrata-Storti Foundation

Language:

English

Submitter:

Verena Zwahlen

Date Deposited:

26 Mar 2015 11:35

Last Modified:

09 Oct 2017 00:09

Publisher DOI:

10.3324/haematol.2013.096537

PubMed ID:

24837466

BORIS DOI:

10.7892/boris.66084

URI:

https://boris.unibe.ch/id/eprint/66084

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