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

Text GMB_20141441 full_Distinct characteristics.pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (784kB)

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).

Interest & Impact

Downloads

1 since deposited on 26 Mar 2015
0 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item