The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia.

Identification of patients at risk of early disease progression is the mainstay of tailored management in chronic lymphocytic leukemia (CLL). Although application of established biomarkers is limited by intrinsic detection/readout complexities, abnormality of κ and λ serum-free light chain ratio [sFLC (κ/λ)] was proposed as a straightforward prognosticator in CLL. By analyzing 449 therapy-naive patients, we show that an abnormal sFLC(κ/λ), along with CD38, ZAP-70, IGHV mutations, cytogenetics and stage, independently predicts treatment-free survival (TFS) but becomes prognostically irrelevant if the cumulative amount of clonal and nonclonal FLCs [sFLC(κ + λ)], a variable associated with cytogenetic risk, exceeds the threshold of 60.

Epigenetic regulation in myelodysplastic syndromes: implications for therapy.

Introduction: Myelodysplastic syndromes (MDS), characterized by ineffective hematopoiesis and dysplasia in one or more lineages, produce life-threatening cytopenias and progress to acute myeloid leukemia (AML). Growing evidence suggests that targeting epigenetic mechanisms improves MDS/AML pathophysiology.

Areas Covered: This review provides an understanding of studies investigating novel agents published up to January 2011 aimed at normalizing and monitoring the epigenetic profile of the MDS cancer cell.

Lenalidomide in the treatment of chronic lymphocytic leukemia.

Introduction: insights into the role of the tumor microenvironment and of immune dysfunction in chronic lymphocytic leukemia (CLL) have opened the way for further augmenting the therapeutic armamentarium for CLL patients. In this respect, lenalidomide represents an exciting drug since it is able to eliminate CLL cells without immunosuppression.

Areas Covered: mechanism of action and clinical trials of lenalidomide in CLL, and suggestions for its future utilization are reviewed.

Janus kinase 2 inhibitors in myeloproliferative disorders.

Importance Of The Field: JAK2 is an obligatory kinase for the proliferation and differentiation of erythroid cells and megakaryocytes thus representing a relevant therapeutic target for agents that specifically inhibit its activity particularly in myeloproliferative disorders (MPD) harboring JAK2(V617F) mutations.

Areas Covered In This Review: We discuss the physiopathology of the JAK2 signaling pathway and review clinical trials of JAK2 inhibitors for the treatment of MPD using papers and meeting abstracts published up to September 2010.

What The Reader Will Gain: This review helps in understanding the potential role of JAK2 inhibitors in MPD clinical trials and provides a comprehensive review regarding their efficacy and safety in these disorders.

Biological and clinical relevance of quantitative global methylation of repetitive DNA sequences in chronic lymphocytic leukemia.

Global DNA hypomethylation affecting repeat sequences has been reported in different cancer types. Herein, we investigated the methylation levels of repetitive DNA elements in chronic lymphocytic leukemia (CLL), their correlation with the major cytogenetic and molecular features, and clinical relevance in predicting therapy-free survival (TFS). A quantitative bisulfite-PCR Pyrosequencing method was used to evaluate methylation of Alu, long interspersed nuclear elements-1 (LINE-1) and satellite-α (SAT-α) sequences in 77 untreated early-stage (Binet A) CLL patients.