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The genetic background of mature B-cell neoplasms with villous lymphocytes is poorly understood. We identified a novel breakpoint region at 14q32.13 that was rearranged together with IGH/14q32.33 in four cases of BRAF/V600E-negative leukemia/lymphoma with villous lymphocytes carrying either t(14;14)(q32.13;q32.33) (three patients) or del(14)(q32.13q32.33) (one patient). The 14q32.13 breakpoints were mapped by fluorescence in situ hybridization (FISH) in the region harboring the TCL1A/ TCL1B/ TCL6 genes, known to be affected by TCRA/ D-mediated t(14;14)(q11;q32)/inv(14)(q11q32) occurring in T-cell leukemia/lymphoma. To identify the target of t(14;14)(q32.13; q32.33) and del(14)(q32.13q32.33), quantitative real-time polymerase chain reaction (qRT-PCR) analysis of 25 candidate genes located centromerically and telomerically to the 14q32.13 breakpoint was performed. Any of the analyzed genes was commonly overexpressed in the presented cases. Of note, up-regulated transcription of TCL1A was observed in two cases. In summary, we provide evidence that IGH-mediated chromosomal aberrations affecting the 14q32.13/ TCL1A- TCL6 region are recurrent in mature B-cell neoplasms with villous lymphocytes. Despite extensive qRT-PCR studies, molecular consequences of these novel aberrations remain elusive. [ABSTRACT FROM AUTHOR]

Hairy cell leukemia variant (HCL-V) is now included in the World Health Organization (WHO) classification as a provisional entity and is no longer considered to be biologically related to classic HCL (HCL-C). The clinical course of HCL-V is variable but usually more aggressive, and the median survival of patients with HCL-V is significantly shorter than that of HCL-C. The therapeutic approach to HCL-V is still debated. Various treatment approaches active in HCL-C achieve partial response (PR) or no response in HCL-V, and remission is usually shorter than in HCL-C. In addition, HCL-V seems to be resistant to therapeutic modalities usually highly effective in the treatment of HCL-C. Cladribine (2-CdA) is significantly less active in HCL-V than in HCL-C. In addition, the majority of patients with HCL-V require more than one cycle of 2-CdA to maintain PR. Patients with HCL-V treated with pentostatin also have a poorer clinical outcome and a lower response rate than those of patients with HCL-C. Recently, some reports indicate that monoclonal antibodies, rituximab and alemtuzumab, are active in HCL-V. Promising results have also been obtained with anti-CD22 immunotoxin, BL22. A new generation of CD22-specific immunotoxins, moxetumomab pasudotox (CAT-8015, HA22), highly active in refractory/relapsed HCL-C, also need clinical investigation in HCL-V. Currently, immunochemotherapy with rituximab and purine nucleoside analogs (PNAs) should be considered as the treatment of choice in previously untreated patients. [ABSTRACT FROM AUTHOR]

Hairy cell leukemia (HCL) variant is a rare low-grade B-cell disorder affecting the elderly or middle-aged population with features intermediate between those of HCL and prolymphocytic leukemia. Unlike HCL, it is resistant to most conventional treatment. We report a case of a 53-year-old man who had refractory thrombocytopenia and lymphocytosis for 8 years. Investigations and analysis of spleen and bone marrow revealed a diagnosis of HCL variant. He opted for treatment with rituximab, a chimeric monoclonal antibody targeting CD20. There was complete recovery of his full blood count and a bone marrow biopsy performed 3 months post-treatment showed complete remission. This is, to our knowledge, the first reported patient with HCL variant for whom treatment with rituximab was successful, and this treatment needs further investigation. [ABSTRACT FROM AUTHOR]