Matrine suppresses cell growth of human chronic myeloid leukemia cells via its inhibition of the interleukin-6/Janus activated kinase/signal transducer and activator of transcription 3 signaling cohort.

Matrine, alkaloid isolated from Sophora flavescens, is known to be pleiotropic by exerting anti-inflammatory, anti-oxidation, as well as anti-cancer effects. However, the precise molecular targets or pathways responsible for its activities still remain unclear. The present study aimed to determine the underlying mechanisms of matrine in inhibiting the chronic myeloid leukemia cells (CML). It was observed that matrine treatment significantly suppressed CML cells proliferation, induced apoptosis and resulted in the accumulation of cells in the G0/G1 phase, accompanied by a significant decrease in Bcl-xL, Cyclin D1, and c-Myc expression. Western blot analyses revealed that matrine treatment resulted in the down-regulation in phospho-STAT3 and phospho-JAK2 without significantly effects on STAT3 and JAK2 protein levels. Matrine significantly reduced the expression of IL-6, a potent upstream activating factor of STAT3. These results strongly suggested the IL-6/JAK/STAT3 pathway play an important role in matrine's anti-leukemia effects in K562 cells.

Efficacy and safety of ruxolitinib in Asian patients with myelofibrosis.

Myelofibrosis is characterized by progressive cytopenias, bone marrow fibrosis, splenomegaly and severe constitutional symptoms. In the phase 3 Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment (COMFORT) studies, ruxolitinib, a potent Janus kinase 1 (JAK1)/JAK2 inhibitor, provided substantial improvements in splenomegaly, symptoms, quality-of-life measures and overall survival compared with placebo or best available therapy. No assessments of the efficacy and safety of ruxolitinib have been conducted in Asian patients. Here, we describe results from an open-label, single-arm, phase 2 trial evaluating ruxolitinib in Asian patients with myelofibrosis (n = 120). The primary endpoint was met, with 31.7% of patients achieving a ≥ 35% reduction from baseline spleen volume at week 24. As measured by the 7-day Myelofibrosis Symptom Assessment Form v2.0, 49% of patients achieved a ≥ 50% reduction from baseline in total symptom score. Adverse events were consistent with those seen in the COMFORT studies. Ruxolitinib was well tolerated in Asian patients with myelofibrosis and provided substantial reductions in splenomegaly and improvements in symptoms.

Detection of BCR-ABL fusion proteins in patients with leukemia using a cytometric bead array.

Rapid and accurate detection of BCR-ABL fusion proteins is vital for the diagnosis and classification of leukemias, especially chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). Recently, the cytometric bead array (CBA) system has been used to identify BCR-ABL proteins in leukemic cell lysates. To evaluate the accuracy of this new technique, we tested 70 patients with hematological diseases using the CBA system, cytogenetic analysis, fluorescence in situ hybridization (FISH) and real-time quantitative polymerase chain reaction (RQ-PCR). Most of the results obtained by the CBA system were concordant with those by cytogenetic analysis, FISH and RQ-PCR. In the CBA system, dilution experiments with positive control samples revealed sensitivities of at least 1%. The statistical analysis revealed that the mean fluorescence intensity (MFI) values of the BCR-ABL fusion proteins from mononuclear cells (MNCs) were higher than those from WBC or BM samples. The MFI values of cells were not dramatically reduced after 24 hours of storage at room temperature. The CBA technique detected all types of BCR-ABL proteins in leukemic cells with high specificity and sensitivity. Therefore, CBAs will contribute to the fast and easy diagnosis of leukemias, the classification of leukemias and the monitoring of minimal residual disease (MRD).

MiR-15a, miR-16-1 and miR-17-92 cluster expression are linked to poor prognosis in multiple myeloma.

Multiple myeloma (MM) is characterized by a profound genomic instability of potential prognostic relevance. Loss of chromosome 13, observed in almost half of patients, negatively affects prognosis. MiR-15a, miR16-1 and miR-17-92 cluster, located on 13q, play important roles in the regulation of cell proliferation, differentiation and apoptosis. Therefore, we investigated a possible correlation of miRNA expression with chromosome 13 deletions (del(13)) and prognosis. We measured the expression of miR-15a, miR16-1 in 70 newly diagnosed MM patients and miR-17-92 cluster in 85 newly diagnosed MM patients by quantitative real-time PCR analyses. MiR-15a, miR-16-1 and miR-17-92 cluster expression levels are independent of the del(13). High levels of miR-15a, miR-16-1, miR-17, miR-20a and miR-92-1 are associated with shorter progression-free survival (PFS), suggesting poor prognosis. Our data suggest that the expression of specific miRNAs may be contributing to MM prognosis.