A new diagnostic algorithm for burkitt and diffuse large B-cell lymphomas based on the expression of CSE1L and STAT3 and on MYC rearrangement predicts outcome

Aggressive mature B-cell non-Hodgkin's lymphomas (BCL) sharing features of Burkitt's lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) (intermediate BL/DLBCL) but deviating with respect to one or more characteristics are increasinglyrecognized. The limited knowledge about these biologically heterogeneous lymphomas hampers their assignment to a known entity, raising incertitude about optimal treatment approaches. We therefore searched for discriminative, prognostic, and predictive factors for their better characterization. Patients and methods: We analyzed 242 cytogenetically defined aggressive mature BCL for differential protein expression.Marker selection was based on recent gene-expression profile studies. Predictive models for diagnosis were established and validated by a different set of lymphomas. Results: CSE1L- and inhibitorof DNA binding-3 (ID3)-overexpression was associated with the diagnosis of BL and signal transduction and transcription-3(STAT3) with DLBCL (P < 0.001 for all markers). All three markers were associated with patient outcome in DLBCL. A new algorithm discriminating BL from DLBCL emerged, including the expression of CSE1L, STAT3,and MYC translocation. This 'new classifier' enabled the identification of patients with intermediate BL/DLBCL who benefited from intensive chemotherapy regimens. Conclusion: The proposed algorithm, which is based on markers with reliable staining properties for routine diagnostics,represents a novel valid tool in separating BL from DLBCL. Most interestingly, it allows segregating intermediate BL/DLBCL into groups with different treatment requirements.