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B-cell prolymphocytic leukemia and chronic lymphocytic leukemia have distinctive gene expression signatures

Leukemia volume 23, pages 2160–2167 (2009)Cite this article

B-cell prolymphocytic leukemia (B-PLL) is a rare disease, characterized by splenomegaly, no lymphadenopathy, marked lymphocytosis with prolymphocytes exceeding 55% of circulating lymphoid cells, poor response to therapy and short survival. First described in the early seventies,1 B-PLL is recognized as a specific entity in the WHO classification.2 Cases of chronic lymphocytic leukemia (CLL) with >10% and <55% prolymphocytes (CLL/PL) have different biological features from B-PLL. Although the immunophenotype of B-PLL is different from CLL, one third of B-PLL cases express CD5.2 Chromosome abnormalities include TP53 gene deletions/mutations, which may explain its aggressive course.3 The expression of CD38 and ZAP-70 and the mutational status of immunoglobulin heavy chain variable region (IgVH) genes are heterogeneous4 and, unlike in CLL, they have no prognostic impact; the IgVH gene family usage in B-PLL is different from CLL, CLL/PL or other lymphomas.4 Nevertheless, the existence of B-PLL as a distinct entity is debated. Therefore, we investigated by microarray analysis, proven useful in the classification of lymphoproliferative disorders, the genomic profile of B-PLL and compared it with CLL to clarify their relationship, to identify differentially expressed transcripts, which may be helpful in diagnostic and therapeutic settings, and to understand B-PLL pathogenesis.

We selected retrospectively cryopreserved blood mononuclear cells containing >95% of malignant cells from 10 de-novo B-PLL and 10 untreated CLL cases. The diagnosis was established by clinical features, lymphocyte morphology and immunophenotype, according to the WHO.2

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Acknowledgements

Professor MF Greaves for useful comments and criticisms to the manuscript. IDG was supported by a Fellowship from the British Society of Haematology; NO was supported by the Arbib foundation; NPJ was supported by a Fellowship from Leukaemia Research UK.

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Authors and Affiliations

  1. Division of Hematology, Department of Cellular Biotechnologies and Hematology, ‘Sapienza’ University, Rome, Italy

    I Del Giudice, S Chiaretti & M Messina

  2. Section of Haemato-Oncology, Institute of Cancer Research, Sutton, Surrey, UK

    N Osuji, V Brito-Babapulle, N Parry-Jones, G Morgan, D Catovsky & E Matutes

  3. Breakthrough Centre, Institute of Cancer Research, Chelsea, London, UK,

    T Dexter

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  1. I Del Giudice
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  2. N Osuji
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Correspondence to E Matutes.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Del Giudice, I., Osuji, N., Dexter, T. et al. B-cell prolymphocytic leukemia and chronic lymphocytic leukemia have distinctive gene expression signatures. Leukemia 23, 2160–2167 (2009). https://doi.org/10.1038/leu.2009.137

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