SummaryProper splicing of pre‐mRNA is required for protein synthesis and therefore is a fundamental cellular function. The discovery of a variety of somatic spliceosomal mutations in haematological malignancies, including myeloid neoplasms and chronic lymphocytic leukaemia has pointed to a new leukaemogenic pathway involving spliceosomal dysfunction. Theoretically, spliceosomal mutations can lead to activation of incorrect splice sites, intron retention or aberrant alternative splicing occurring in patterns generated by mutations of individual spliceosomal proteins. Such events can produce a defective balance between protein isoforms leading to functional consequences including defective regulation of proliferation and differentiation. The observed pattern of occurrence of highly specifi...

We recently took care of an 84 year old man with chronic lymphocytic leukemia and malignant melanoma of the head and neck. He had previously undergone several unsuccessful surgical procedures, including a Mohs procedure for resection of melanoma. He came to us for definitive wide area resection as well as skin grafting and sentinel lymph node biopsy. Laboratory values during a visit to our preoperative clinic 6 days before surgery were significant for a white blood cell count of 179 × 103 cells/uL (89% lymphocytes and less than 5% prolymphocytes) and serum potassium of 6.0 mmol/L (normal: 3.5 - 5.5 mmol/L). No evidence of hyperkalemia was noted on electrocardiogram (ECG) taken during the visit. (Source: Journal of Clinical Anesthesia)

Trafficking of B-cell chronic lymphocytic leukemia (CLL) cells to the bone marrow and interaction with supporting stromal cells mediates important survival and proliferation signals. Previous studies have demonstrated that deletion of Rhoh led to a delayed disease onset in a murine model of CLL. Here we assessed the impact of RhoH on homing, migration, and cell-contact dependent interactions of CLL cells. Rhoh–/– CLL cells exhibited reduced marrow homing and subsequent engraftment. In vitro migration toward the chemokines CXCL12 and CXCL13 and cell-cell interactions between Rhoh–/– CLL cells and the supporting microenvironment was reduced. In the absence of RhoH the distribution of phosphorylated focal adhesion kinase, a protein known to coordinate activation of the...

Authors: Charafeddine KM, Jabbour MN, Kadi RH, Daher RT Abstract Serum free light chain (sFLC) assays were shown to improve detection, management, and prognostication in plasma cell disorders. Recently, sFLC assays improved detection of M proteins when combined with standard methods of protein electrophoresis/immunofixation in patients with non-Hodgkin lymphoma/chronic lymphocytic leukemia (NHL/CLL). Incidence of abnormal sFLC ratio (sFLCr) varied from 0% to 36% and 29.7% to 59% in NHL and CLL, respectively. Increased sFLC levels or abnormal sFLCr predict shorter overall survival in early-stage CLL. Furthermore, abnormal sFLCr correlated with advanced disease stage and poorer outcome. In diffuse large B-cell lymphomas, increased sFLC was demonstrated as an independent, adverse prog...

(Ohio State University Medical Center) The experimental drug ibrutinib shows great promise for the treatment of elderly patients with chronic lymphocytic leukemia (CLL), according to interim findings from a clinical trial. The findings indicate the oral agent deserves further study as a first-line treatment in elderly CLL patients. CLL, the most common form of leukemia, is currently incurable. (Source: EurekAlert! - Cancer)