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Errata corrige

2014-01-01T00:00:00Z

Title: Errata corrige

Monoclonal B-cell lymphocytosis

2014-01-01T00:00:00Z

Title: Monoclonal B-cell lymphocytosis Authors: D'Arena, Giovanni; Musto, Pellegrino Abstract: Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic hematologic condition defined by the presence of a small (<5 x 109/L) clonal B-cell population in the peripheral blood in the absence of lymph-node enlargement, cytopenias or autoimmune diseases. It is found in approximately 3-12% of normal persons depending on the accuracy of analytical techniques applied. According to the immunophenotypic profile of clonal B-cells, the majority of MBL cases (75%) are classified as chronic lymphocytic leukemia (CLL)-like. This form may progress into CLL at a rate of 1–2% per year. It is thought that CLL is always preceded by MBL. The remaining MBL cases are defined as atypical CLL-like (CD5+/CD20bright) and CD5- MBL. The MBL clone size is quite heterogenous. Accordingly, two forms of MBL are identified: i) high-count, or ‘clinical’ MBL, in which an evidence of lymphocytosis (<5 x 109/L clonal B-cells) is seen, and ii) a low-count MBL, in which a normal leukocyte count is found and that is identified only in population-screening studies. Both forms of MBL may carry the cytogenetic abnormalities that are the hallmark of CLL, including 13q-, 17p- and trisomy 12. Consistent with the indolent phenotype of this condition, genetic lesions, such as TP53, ATM, NOTCH1 and SF3B1 mutations, usually associated with high-risk CLL, are rarely seen. Overall, no prognostic indicator of evolution of MBL to overt CLL has been found at present time. However, taking into account this possibility, a clinical and lab monitoring (at least annually), is recommended.

Current Concepts on Diagnosis and Treatment of Mastocytosis

2014-01-01T00:00:00Z

Title: Current Concepts on Diagnosis and Treatment of Mastocytosis Authors: Magliacane, Diomira; Parente, Roberto; Triggiani, Massimo Abstract: Mastocytosis is a heterogeneous group of disorders characterized by a clonal proliferation and accumulation of mast cells in one or more organ, primarily in the skin and bone marrow. The clinical spectrum of the disease varies from relatively benign forms with isolated skin lesions to very aggressive variants with extensive systemic involvement and poor prognosis. The growth and proliferation of clonal mast cells is caused by an activating mutation of the tyrosine kinase receptor Kit for Stem Cell Factor, the main growth factor for mast cells. Clinical symptoms are related to mast-cell mediator release, to the tissue mast cell infiltration or both. The degree of infiltration and cell activation determines the highly variable clinical and morphological features. Current treatment of mastocytosis includes symptomatic, antimediator drugs and cytoreductive targeted therapies.

Molecular Genetics of Myelofibrosis and its associated Disease Phenotypes

2014-01-01T00:00:00Z

Title: Molecular Genetics of Myelofibrosis and its associated Disease Phenotypes Authors: Tabarroki, Ali; Tiu, Ramon V. Abstract: In 2005, the discovery of Janus kinase 2 (JAK2) V617F mutation in approximately half of patients with myelofibrosis (MF) marked an important milestone in our understanding of the pathophysiology of MF. This has broadened our understanding of the disease pathogenesis and became the foundation for the development and subsequent clinical use of JAK inhibitors for MF. However, it is clear that other pathogenetic modifiers contribute to the disease diversity and phenotypic variability of MF. Novel genome scanning technologies were useful in the identification of recurrent molecular mutations in other genes including MPL, TET2, IDH1/2, DNMT3A, SH3B2 (LNK) and CBL in MF pointing out that other pathways might be important in addition to the JAK/STAT pathway. The biologic role and clinical implications of these molecular mutations in MF is currently under investigation. The main challenge is to understand the mechanisms whereby molecular mutations whether alone or in combination with other genetic and non-genetic events contribute to the pathogenesis of MF and eventually can explain the phenotypic variability among the MF patients. In the present review we will provide an overview of the molecular pathogenesis of MF describing past and recent discoveries in molecular markers and their possible relevance in disease phenotype.