| Autor: |
Thai Hoa Tran, Marian H. Harris, Jonathan V. Nguyen, Traci M. Blonquist, Kristen E. Stevenson, Eileen Stonerock, Barbara L. Asselin, Uma H. Athale, Luis A. Clavell, Peter D. Cole, Kara M. Kelly, Caroline Laverdiere, Jean-Marie Leclerc, Bruno Michon, Marshall A. Schorin, Jennifer J.G. Welch, Shalini C. Reshmi, Donna S. Neuberg, Stephen E. Sallan, Mignon L. Loh, Lewis B. Silverman |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
|
| Zdroj: |
Blood Advances, Vol 2, Iss 5, Pp 529-533 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
2473-9529 |
| DOI: |
10.1182/bloodadvances.2017014704 |
| Popis: |
Abstract: Recurrent chromosomal rearrangements carry prognostic significance in pediatric B-lineage acute lymphoblastic leukemia (B-ALL). Recent genome-wide analyses identified a high-risk B-ALL subtype characterized by a diverse spectrum of genetic alterations activating kinases and cytokine receptor genes. This subtype is associated with a poor prognosis when treated with conventional chemotherapy but has demonstrated sensitivity to the relevant tyrosine kinase inhibitors. We sought to determine the frequency of kinase-activating fusions among National Cancer Institute (NCI) high-risk, Ph-negative, B-ALL patients enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 05-001 and to describe their associated clinical characteristics and outcomes. Among the 105 patients screened, 16 (15%) harbored an ABL-class fusion (ETV6-ABL1: n = 1; FOXP1-ABL1: n = 1; SFPQ-ABL1: n = 1; ZC3HAV1-ABL2: n = 1) or a fusion activating the JAK-STAT pathway (P2RY8-CRLF2: n = 8; PAX5-JAK2: n = 4). Sixty-nine percent of patients with an identified fusion had a concomitant IKZF1 deletion (n = 11). In univariate analysis, fusion-positivity and IKZF1 deletion were each associated with inferior event-free survival; IKZF1 deletion retained statistical significance in multivariable analysis (hazard ratio, 2.64; P = .019). Our findings support therapy intensification for IKZF1-altered patients, irrespective of the presence of a kinase-activating fusion. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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