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Acute Lymphocytic Leukemia

Molecular heterogeneity of sporadic adult Burkitt-type leukemia/lymphoma as revealed by PCR and cytogenetics: correlation with morphology, immunology and clinical features

Abstract

Chromosomal translocations involving the MYC oncogene are a hallmark of Burkitt lymphoma but they are only found in a varying frequency in mature Burkitt-type acute lymphoblastic leukemia (B-ALL). We have investigated samples of 56 sporadic Burkitt leukemia/lymphoma patients for the translocations t(8;14)(q24;q32), t(2;8)(p11;q24) and t(8;22)(q24;q11). Long PCR was used for detecting the immunoglobulin heavy chain (IgH) translocation and cytogenetics and/or fluorescence in situ hybridization for detecting the ‘variant’ MYC translocations. A total of 29 samples (51.8%) were t(8;14)-positive by long PCR. Approximately one-third had a chromosomal breakpoint in the IgH joining region while the others had breakpoints in the IgH switch regions. Among them were two cases with a previously unreported MYC translocation into the IgE switch region. Long PCR was more reliable compared to conventional cytogenetics for detecting the t(8;14). Epstein–Barr virus was detected in high copy number in two (3.6%) t(8;14)-positive cases by real-time quantitative PCR. Human herpesvirus 8 was not detected in any case by nested PCR. A typical L3 or L3-compatible cytomorphology was highly predictive (>80%) but not specific of a MYC translocation. A total of 34 patients were treated according to the GMALL B-ALL therapy protocols and there was no significant difference in overall survival between patients with or without t(8;14).

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Acknowledgements

TB, HR and SS received a grant from the Deutsche Krebshilfe (grant 10-1988-Bu1) for this study. ET, DH, HAH and NG were also supported by the Deutsche Krebshilfe (Grant 70-2657-Ho2). We thank all participating clinics of the GMALL B-ALL/B-NHL therapy study and cytogenetic laboratories, especially Dr C Schoch (München), for their support. We particularly indebted to A Sindram, M Molkentin and C Seide (all Berlin) for PCR analysis, B Komischke and R Lippoldt (both Berlin) for immunophenotyping, I Bachmann (Marburg) for cytogenetic and FISH analysis and M Rojewski (now Ulm/Germany) for help with cell culture.

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Burmeister, T., Schwartz, S., Horst, HA. et al. Molecular heterogeneity of sporadic adult Burkitt-type leukemia/lymphoma as revealed by PCR and cytogenetics: correlation with morphology, immunology and clinical features. Leukemia 19, 1391–1398 (2005). https://doi.org/10.1038/sj.leu.2403847

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