Subject(s)
Gene Expression Profiling , Leukemia, Lymphocytic, Chronic, B-Cell , Survival Analysis , Adult , Aged , Aged, 80 and over , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Male , Middle Aged , Real-Time Polymerase Chain ReactionABSTRACT
Molecular characterization of acute lymphoblastic leukemia (ALL) has greatly improved the ability to categorize and prognostify patients with this disease. In this study, we show that the proto-oncogene CDX2 is aberrantly expressed in the majority of cases with B-lineage ALL and T-ALL. High expression of CDX2 correlated significantly with the ALL subtype pro-B ALL, cALL, Ph(+) ALL and early T-ALL. Furthermore, high expression of CDX2 was associated with inferior overall survival and showed up as a novel and strong risk factor for ALL in bivariate analysis. Functional analyses showed that overexpression of Cdx2 in murine bone marrow progenitors perturbed genes involved in lymphoid development and that depletion of CDX2 in the human ALL cell line Nalm6 inhibited colony formation. These data indicate that aberrant CDX2 expression occurs frequently and has prognostic impact in adult patients with ALL.
Subject(s)
Gene Expression Regulation, Neoplastic , Genes, Homeobox , Homeodomain Proteins/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Adult , Aged , Aged, 80 and over , Animals , Bone Marrow Cells/pathology , CDX2 Transcription Factor , Cell Line, Tumor , Female , Homeodomain Proteins/analysis , Humans , Male , Middle Aged , Neoplasm Proteins/analysis , Neoplasm Proteins/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/classification , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prognosis , Proto-Oncogene Mas , Proto-Oncogenes , Survival Rate , Young AdultABSTRACT
The extracellular matrix (ECM) component hyaluronan (HA) is considered to contribute to the optimal development of the gametes and the embryo. In this study, the regulation and localization of HA, its synthases (HAS 1-3) and the receptors CD44, RHAMM, and putative HARE were investigated in bovine oviducts during the estrous cycle. HA could be demonstrated in the entire lamina propria of the oviduct. Immunoreactive CD44 was found in the muscle layer additionally to the lamina propria. As for HA the luminal epithelium was devoid of CD44. Introducing quantitative real-time RT-PCR, a remarkable cyclic change of CD44 occurred. In addition, CD44 expression was much higher in the isthmus than in the ampulla. RHAMM transcripts were elevated particularly in the ampulla during estrus. A major part of the bovine putative HARE coding sequence was characterized. An analysis of the tissue distribution revealed transcripts not restricted to liver, spleen, and lymph node, providing evidence for a local putative HARE-mediated turnover of HA. These results suggest that in the bovine oviduct the cell surface receptor CD44 in particular might inversely regulate HA during the estrous cycle. The local turnover of HA through synthases and receptors may indicate its participation in the bovine oviduct supporting gamete maturation and early embryonic development.
