Translocation t(2;7)(p12;q21-22) with dysregulation of the CDK6 gene mapping to 7q21-22 in a non-Hodgkin’s lymphoma with leukemia

Background and Objectives. A female patient presented with splenomegaly and lymphocytosis with atypical lymphoid cell morphology, We identified t(2;7)(p12;q21) prompting studies of the translocation breakpoint and its consequences on protein expression to confirm or otherwise the recently reported involvement of CDK6 and IG kappa genes in the t(2;7) leading to over-expression of CDK6 protein. Design and Methods. A variety of clinical and laboratory techniques including cell marker, cytogenetic and histologic studies were applied in order to establish the diagnosis. Fluorescence in situ hybridization (FISH) and Southern blotting were used for mapping the translocation breakpoint and Western blotting for assessing protein expression. Results. Immunophenotyping showed the presence of a B-cell population with strong expression of FMC7, CD22, CD79b, CD5 and K restricted surface immunoglobulins. Based on morphology and immunophenotypic markers the diagnosis of B-cell nonHodgkin’s lymphoma was made. Karyotyping revealed a clone with t(2;7)(p12;q21-22). Evidence for clonal evolution with additional abnormalities including a deletion of the TP53 was present, We established by FISH and Southern blotting that the breakpoint on 7q21-22 fell in a region 66kb telomeric to the previously reported breakpoint for the t(2;7) and was the same as that observed in a t(7;21). CDK6 protein was over-expressed. The patient received alkylating agents and splenectomy and is alive but the lymphocytosis persists with evidence of disease progression. Interpretations and Conclusions. We have demonstrated that CDK6 expression is dysregulated even when the breakpoint on 7q21-22 is located 66kb upstream from the coding region. Interestingly, the precise assignment of the lymphoma type in our case was not possible even when the splenic histology was analyzed. (C)2002, Ferrata Storti Foundation

Multi-label classification using ensembles of pruned sets

This paper presents a Pruned Sets method (PS) for multi-label classification. It is centred on the concept of treating sets of labels as single labels. This allows the classification process to inherently take into account correlations between labels. By pruning these sets, PS focuses only on the most important correlations, which reduces complexity and improves accuracy. By combining pruned sets in an ensemble scheme (EPS), new label sets can be formed to adapt to irregular or complex data. The results from experimental evaluation on a variety of multi-label datasets show that [E]PS can achieve better performance and train much faster than other multi-label methods

The diagnosis of BCR/ABL-negative chronic myeloproliferative diseases (CMPD): a comprehensive approach based on morphology, cytogenetics, and molecular markers

Recent years showed significant progress in the molecular characterization of the chronic myeloproliferative disorders (CMPD) which are classified according to the WHO classification of 2001 as polycythemia vera (PV), chronic idiopathic myelofibrosis (CIMF), essential thrombocythemia (ET), CMPD/unclassifiable (CMPD-U), chronic neutrophilic leukemia, and chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome, all to be delineated from BCR/ABL-positive chronic myeloid leukemia (CML). After 2001, the detection of the high frequency of the JAK2V617F mutation in PV, CIMF, and ET, and of the FIP1L1–PDGFRA fusion gene in CEL further added important information in the diagnosis of CMPD. These findings also enhanced the importance of tyrosine kinase mutations in CMPD and paved the way to a more detailed classification and to an improved definition of prognosis using also novel minimal residual disease (MRD) markers. Simultaneously, the broadening of therapeutic strategies in the CMPD, e.g., due to reduced intensity conditioning in allogeneic hematopoietic stem cell transplantation and the introduction of tyrosine kinase inhibitors in CML, in CEL, and in other ABL and PDGRFB rearrangements, increased the demands to diagnostics. Therefore, today, a multimodal diagnostic approach combining cytomorphology, cytogenetics, and individual molecular methods is needed in BCR/ABL-negative CMPD. A stringent diagnostic algorithm for characterization, choice of treatment, and monitoring of MRD will be proposed in this review

Hairy cell leukemia (HCL) and hairy cell leukemia variant (HCL-V)

Review on Hairy cell leukemia (HCL) and hairy cell leukemia variant (HCL-V), with data on clinics, and the genes involved

Classification of T-cell disorders

Review on Classification of T-cell disorders, with data on clinics, and the genes involved