IKZF1 status as a prognostic feature in BCR-ABL1-positive childhood ALL

Arian Van Der Veer, Marketa Zaliova, Federica Mottadelli, Paola De Lorenzo, Gertruuy Te Kronnie, Christine J. Harrison, Hélène Cavé, Jan Trka, Vaskar Saha, Martin Schrappe, Rob Pieters, Andrea Biondi, Maria Grazia Valsecchi, Martin Stanulla, Monique L. Den Boer, Giovanni Cazzaniga

Research output: Contribution to journalArticleAcademicpeer-review

46 Citations (Scopus)


Childhood BCR-ABL1-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has an unfavorable outcome and is characterized by a high frequency of IKZF1 deletions. The prognostic value of IKZF1 deletions was evaluated in two cohorts of children with BCR-ABL1-positive BCP-ALL, before (pre-TKI) and after introduction of Imatinib (EsPhALL). IKZF1 deletions were found in 126/191 (66%) of the patients. In the pre-TKI cohort, IKZF1-deleted patients had an unfavorable outcome compared to wild-type patients (4-yr DFS 30.0±6.8% versus 57.5±9.4%, p=0.01). In the EsPhALL-cohort, the IKZF1 deletions were associated with an unfavorable prognosis in patients who were stratified by early clinical response in the good-risk arm (4-yr DFS 51.9±8.8% for IKZF1-deleted versus 78.6±13.9% for IKZF1 wild-type; p=0.03), even when treated with Imatinib (4-yr DFS 55.5±9.5% for IKZF1-deleted versus 75.0±21.7% for IKZF1 wild-type; p=0.05). In conclusion, IKZF1 deletions are predictive for a highly unfavorable outcome in children with BCR-ABL1-positive BCP-ALL irrespective the introduction of Imatinib. These results underscore the urgent need for alternative therapy for IKZF1-deleted BCR-ABL1-positive patients. In contrast, good-risk patients with IKZF1 wild-type responded remarkably well to Imatinib-containing regimens, thus providing a rationale to potentially avoid the use of hematopoietic stem cell transplantation in this subset of BCR-ABL1-positive children.
Original languageEnglish
Pages (from-to)1691-1698
Number of pages8
Issue number11
Publication statusPublished - 13 Mar 2014


  • GENE

Cite this

Van Der Veer, A., Zaliova, M., Mottadelli, F., De Lorenzo, P., Te Kronnie, G., Harrison, C. J., Cavé, H., Trka, J., Saha, V., Schrappe, M., Pieters, R., Biondi, A., Valsecchi, M. G., Stanulla, M., Den Boer, M. L., & Cazzaniga, G. (2014). IKZF1 status as a prognostic feature in BCR-ABL1-positive childhood ALL. Blood, 123(11), 1691-1698. https://doi.org/10.1182/blood-2013-06-509794