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Deletion on the long arm of chromosome 11 occurs in 5-20% of chronic lymphocytic leukaemia (CLL) patients. We analysed clinical-biological characteristics of 131 CLL patients carrying 11q deletion documented before therapy ( de novo 11q deleted CLL). De novo 11q deleted CLL were characterized by high frequencies of unmutated immunoglobulin variable heavy genes, multiple fluorescence in situ hybridization aberrations and lymph node involvement. Factors significantly associated with shorter time to first treatment (TTFT) were advanced Binet stages, high white blood cell count, increased β2-microglobulin levels, 17p in addition, splenomegaly and more extensive lymphadenopathy. We found that patients with <25% 11q deleted nuclei ( n = 22) experienced longer TTFT compared with patients with ≥25% 11q deleted nuclei ( n = 87; median TTFT, 40 vs. 14 months, p = 0.011) and also showed better response to treatments (complete response, 50% vs. 21%, p = 0.016). The variables identified by multivariate analysis as independently associated with reduced TTFT were advanced Binet stages [hazard ratio (HR) 4.69; p < 0.001] and ≥25% 11q deleted nuclei (HR 4.73; p = 0.004). De novo 11q deleted CLLs exhibit variable clinical outcome. The percentage of deleted nuclei inside leukemic clone should be included in the prognostic definition of therapy-naïve 11q deleted CLL patients. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Hairy cell Leukaemia (HCL) is a rare neoplasm of peripheral B cells which represents a paradox in oncology. Despite its largely unknown origin and behaviour, HCL is one of the few example of dramatic success in the treatment of a malignancy. The recent steps forward to understanding the biology of HCL from immunogenetic and genomic studies have recently provided new insight into diagnosis and prognosis. Several data from immunoglobulin gene (IG) analysis have provided hints regarding the cell of origin and the ongoing selective interactions of the tumour BCR with environmental stimuli. It has also recently emerged that an unmutated status of the HCL IG can be associated with failure to respond to cladribine, genetic abnormalities indicative of poor outcome and aggressive disease. These observations suggest a central role of the tumour B-cell receptor in defining the outcome of HCL and that that IG gene analysis may have biological and prognostic relevance. Hopefully, IG analysis will help tailor treatment strategies for the most aggressive cases. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Richter's syndrome (RS) represents the transformation of chronic lymphocytic leukaemia (CLL) to aggressive lymphoma and is mostly represented by diffuse large B-cell lymphoma (DLBCL), with a post-germinal centre (GC) phenotype, clonally related to the pre-existing CLL. RS has a very poor prognosis and its pathogenetic mechanisms are poorly understood. In order to gain additional hints in RS pathogenesis, we performed a genome-wide DNA profiling study of 13 RS phases and eight matched CLL phases using the Affymetrix Human Mapping 250K NspI SNP arrays. Individual genomic profiles were heterogeneous, with no individual lesions occurring in more than half of the cases. However, several observations suggest that MYC pathway might be involved in RS. The 13q13.3-qter region containing MIRHG1 (MIR-17-92), a cluster of microRNA interacting with c-MYC, was acquired at the time of transformation. The 13q gain was coupled with the gain of c-MYC and loss of TP53. Translocation of c-MYC was acquired at transformation in a fraction of cases and this event appeared mutually exclusive with gain of MIRHG1. MYCN, a c-MYC homologue, was also recurrently gained. By comparing RS with 48 de novo DLBCL, RS presented a significantly lower prevalence of deletions affecting the PRDM1 and TNFAIP3, genes on 6q, known to be associated with a post-GC phenotype. In conclusion, the genomic profile of RS seems to differ from what observed in de novo DLBCL and in other transformed DLBCL. Genomic lesions occurring in RS are heterogeneous suggesting the existence of different RS subsets, possibly due to different transforming mechanisms. A deregulation of MYC pathway might represent one of the main transformation events in the pathogenesis of a subset of RS clonally related to the previous CLL. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]