Reciprocal leukemia-stroma VCAM-1/VLA-4-dependent activation of NF-κB mediates chemoresistance.

Leukemia cells are protected from chemotherapy-induced apoptosis by their interactions with bone marrow mesenchymal stromal cells (BM-MSCs). Yet the underlying mechanisms associated with this protective effect remain unclear. Genome-wide gene expression profiling of BM-MSCs revealed that coculture with leukemia cells upregulated the transcription of genes associated with nuclear factor (NF)-κB signaling.

CD105 (endoglin) is highly overexpressed in a subset of cases of acute myeloid leukemias.

Objectives: To assess CD105 (endoglin) expression in 119 acute myeloid leukemia (AML) and 13 control cases using immunohistochemistry.

Methods: CD105 expression was assessed retrospectively by using immunohistochemistry in bone marrow specimens.

Results: CD105 was strongly and diffusely positive in all 9 (100%) AMLs with t(15;17)(q24.

Over-expression of CYP2E1 mRNA and protein: implications of xenobiotic induced damage in patients with de novo acute myeloid leukemia with inv(16)(p13.1q22); CBFβ-MYH11.

Environmental exposure to benzene occurs through cigarette smoke, unleaded gasoline and certain types of plastic. Benzene is converted to hematotoxic metabolites by the hepatic phase-I enzyme CYP2E1, and these metabolites are detoxified by the phase-II enzyme NQO1. The genes encoding these enzymes are highly polymorphic and studies of these polymorphisms have shown different pathogenic and prognostic features in various hematological malignancies.

Analysis of Aurora kinase A expression in CD34(+) blast cells isolated from patients with myelodysplastic syndromes and acute myeloid leukemia.

Aurora kinase A, also known as aurora A, is a serine/threonine kinase that plays critical roles in mitosis entry, chromosome alignment, segregation, and cytokinesis. Overexpression of aurora A has been observed in many solid tumors and some hematopoietic neoplasms, but little is known about its expression in myeloid diseases. Because cytogenetic abnormalities play an essential role in the pathogenesis of myeloid malignancies, we hypothesized that aurora A deregulation may be involved in myelodysplastic syndromes and acute myeloid leukemia and contribute to the chromosomal instability observed in these diseases.

Aurora-A kinase nuclear expression in chronic lymphocytic leukemia.

Aurora-A kinase is a cell-cycle-regulating kinase required for chromosomal segregation. Overexpression of Aurora-A kinase has been shown to correlate with tumor proliferation and chromosomal instability. We investigated Aurora-A kinase expression in peripheral blood and bone marrow of 47 chronic lymphocytic leukemia patients and 20 age-matched hematologically healthy subjects.

Immunohistochemical analysis of CBFbeta-SMMHC protein reveals a unique nuclear localization in acute myeloid leukemia with inv(16)(p13q22).

The inv(16)(p13q22) or, less commonly the t(16;16)(p13;q22), is characteristic of acute myeloid leukemia (AML) with abnormal bone marrow eosinophils, also known as AML-M4Eo. This abnormality creates a fusion gene, 5' core binding factor beta (CBF-beta) gene and the 3' MYH11 gene, the latter encoding smooth muscle myosin heavy chain gene (SMMHC). Detection of this abnormality is important for diagnosis and is most commonly done by cytogenetics or molecular methods.

Nuclear BCL-10 expression is common in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia and does not correlate with p65 NF-kappaB activation.

B-cell lymphoma 10 (BCL-10) is expressed in the cytoplasm of normal germinal center and marginal zone B-cells and is involved in lymphocyte development and activation. Aberrant nuclear expression of BCL-10 occurs in a subset of extranodal marginal zone B-cell lymphomas (MALT lymphomas), primarily those with the t(1;14)(p22;q32) or t(11;18)(q21;q21). Little is known about BCL-10 expression in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM).

Expression of constitutively active nuclear-kappa B RelA transcription factor in blasts of acute myeloid leukemia.

The nuclear transcription factor NF-kappa B regulates cell survival, proliferation, and differentiation. Little is known about NF-kappa B in myeloid malignancies. In this report, we assessed NF-kappa B in a group of myeloid neoplasms by using an electrophoretic mobility shift assay (EMSA) and immunofluorescence methods in freshly isolated leukemia cells.