We analyzed in B-chronic lymphocytic leukemia (B-CLL) whole blood assays the activity of therapeutic mAbs alemtuzumab, rituximab, and type II glycoengineered anti-CD20 mAb GA101. Whole blood samples were treated with Abs, and death of CD19(+) B-CLL was measured by flow cytometry. Alemtuzumab efficiently lysed B-CLL targets with maximal lysis at 1-4 h (62%). In contrast, rituximab induced a more...

PURPOSE Gene expression profiling identified receptor tyrosine kinase ROR1, an embryonic protein involved in organogenesis, as a signature gene in B-cell chronic lymphocytic leukemia (B-CLL). To assess the suitability of ROR1 as a cell surface antigen for targeted therapy of B-CLL, we carried out a comprehensive analysis of ROR1 protein expression. EXPERIMENTAL DESIGN Peripheral blood mononuc...

Deletions of the 13q14 chromosome region are associated with B-cell chronic lymphocytic leukemia (B-CLL) and several other types of cancer, suggesting the presence of a tumor suppressor gene. In previous studies the minimal region of deletion (MDR) was mapped to a less than 300-kilobase (kb) interval bordered by the markers 173a12-82 and 138G4/1.3R. For the identification of the putative tumor ...

Peripheral blood chronic lymphocytic leukemia (CLL) cells are quiescent but have active transcription and translation processes, suggesting that these lymphocytes are metabolically active. Based on this premise, the metabolic phenotype of CLL lymphocytes was investigated by evaluating the two intracellular ATP-generating pathways. Metabolic flux was assessed by measuring glycolysis as extracell...

BACKGROUND Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton's tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK). The relative importance of inhibiting these 2 kinases has not been examined despite its relevance to immune-based therapies. METHODS Peripheral blood mononuclear cells from chronic lymphocytic leukemia (CLL) patients on clinical trials of ib...

A growing body of studies highlights involvement of neutrophils in cancer development and progression. Our aim was to assess the phenotypic and functional properties of circulating neutrophils from patients with chronic lymphocytic leukemia (CLL). The percentage of CD54+ and CD64+ neutrophils as well as CD54 expression on these cells were higher in CLL patients than in age-matched healthy contr...

In this issue of Blood, Dubovsky et al use novel methodology to identify lymphocyte cytosolic protein-1 (LCP1) as a putative tumor-associated antigen, Ag (TAA) that may play a critical role in regulating CLL cell homing to the leukemia niche. Their translational research approach further shows that kinase inhibitors (KIs) have the potential to block LCP1 activation, which raises the possibility...

ABT-737 and its orally active analog, ABT-263, are rationally designed inhibitors of BCL2 and BCL-X(L). ABT-263 shows promising activity in early phase 1 clinical trials in B-cell malignancies, particularly chronic lymphocytic leukemia (CLL). In vitro, peripheral blood CLL cells are extremely sensitive to ABT-737 (EC(50) approximately 7 nM), with rapid induction of apoptosis in all 60 patients ...

Background and purpose: Cytotoxic effects of Ligustrum vulgare leaves on HeLa cervical tumor cells suggested that extracts should be investigated as potential anticancer agents. Therefore, we examined a antileukemic activity methanolic fruit two types leukemia cells, MOLT-4 JVM-13, lymphocytes isolated from the blood 33 chronic lymphocytic (CLL) patients mononuclear leukocytes 18 healthy indivi...

In the present study we investigated in vivo therapeutic potential of DCs vaccines in B-cell chronic lymphocytic leukemia (B-CLL). On the day 0 the SCID mice were intraperitoneally inoculated with peripheral blood mononuclear cells (PBMC) of B-CLL patients at a dose of 10-30 x 10(6) and left untreated (controls) or i.p. injected on the day 7 with 0.2 - 14.0 x 10(6) dendritic cells. DCs were gen...