Carlo M. Croce

Bio: Carlo M. Croce is an academic researcher from Ohio State University. The author has contributed to research in topics: microRNA & Cancer. The author has an hindex of 198, co-authored 1135 publications receiving 189007 citations. Previous affiliations of Carlo M. Croce include University of Nebraska Medical Center & University of California, Los Angeles.

Molecular Basis of Mature T-Cell Leukemia

Abstract: T-cell chronic lymphocytic/prolymphocytic leukemia (T-CLL/T-PLL) is a lymphoproliferative disease derived from immunocompetent post-thymic T cells. Activation (initiation of expression) of the TCL1 locus at chromosome 14q32.1 appears to be the causal event in the pathogenesis of these mature T-cell leukemias. This activation occurs as a result of translocations or inversions that cause rearrangement of the TCL1 (T-cell leukemia/lymphoma 1) locus with regulatory elements of T-cell receptor genes. To describe the molecular events that take part in the leukemogenesis of mature T-cell leukemias, we reviewed the literature and our own data on the molecular basis of mature T-cell leukemia. This data search revealed that 4 genes have been identified at the TCL1 locus: TCL1, TCL1b, TNG1, and TNG2. The expression of these genes is substantially increased following rearrangements involving 14q32.1. Functional analysis of the Tcl1 protein revealed its involvement in an Akt (protein kinase B) prosurvival pathway through its interaction with the Akt kinase, which promotes translocation of Akt to the nucleus and increases Akt's enzymatic activity. The available data provide important insights into the molecular mechanisms of T-cell leukemogenesis that may lead to the development of new drugs for treatment of mature T-cell leukemia.

The role of chromosomal translocations in B- and T-cell neoplasia.

Abstract: At the turn of the century, Boveri (1) suggested that abnormal chro­ mosomal patterns in tumor samples reflect the processes responsible for the development of the malignant phenotype. However, the first demonstrated association of a consistent chromosomal rearrangement with a specifi c disease did not occur until 1960 when a marker chromosome, the Phi­ ladelphia chromosome (Ph +), was discovered to be consistently associated with chronic myelogenous leukemia (CML) (2). The Ph+ chromosome was subsequently shown to result from a reciprocal translocation between chromosomes 9 and 22 (3). Due to the introduction of new techniques for "high resolution" ban­ ding-analysis of chromosomes, a large majority of human cancer cells are now known to carry clonal cytogenetic changes (4). This has been most clearly demonstrated for the hematopoietic malignancies and has resulted in a renewed focus on chromosomal rearrangements as a causative factor in malignant transformation. While this view was originally not widely accepted outside of the discipline of cytogenetics, the painstaking efforts to observe and catalogue these rearrangements have now been justifi ed. The application of the new technologies of molecular biology and somatic cell genetics have allowed the characterization of a variety of chromosomal abnormalities, and in particular chromosomal translocations, at the mol-

Functional implications of microRNAs in acute myeloid leukemia by integrating microRNA and messenger RNA expression profiling

Abstract: Our results indicate that by integrating the transcriptome and microRNome in AML cells, it is possible to identify previously unidentified putative functional miRNA-mRNA interactions in AML.

Down-regulation of homeobox genes MEIS1 and HOXA in MLL-rearranged acute leukemia impairs engraftment and reduces proliferation

Abstract: Rearrangements of the MLL (ALL1) gene are very common in acute infant and therapy-associated leukemias. The rearrangements underlie the generation of MLL fusion proteins acting as potent oncogenes. Several most consistently up-regulated targets of MLL fusions, MEIS1, HOXA7, HOXA9, and HOXA10 are functionally related and have been implicated in other types of leukemias. Each of the four genes was knocked down separately in the human precursor B-cell leukemic line RS4;11 expressing MLL-AF4. The mutant and control cells were compared for engraftment in NOD/SCID mice. Engraftment of all mutants into the bone marrow (BM) was impaired. Although homing was similar, colonization by the knockdown cells was slowed. Initially, both types of cells were confined to the trabecular area; this was followed by a rapid spread of the WT cells to the compact bone area, contrasted with a significantly slower process for the mutants. In vitro and in vivo BrdU incorporation experiments indicated reduced proliferation of the mutant cells. In addition, the CXCR4/SDF-1 axis was hampered, as evidenced by reduced migration toward an SDF-1 gradient and loss of SDF-1–augmented proliferation in culture. The very similar phenotype shared by all mutant lines implies that all four genes are involved and required for expansion of MLL-AF4 associated leukemic cells in mice, and down-regulation of any of them is not compensated by the others.

Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.

Abstract: The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original. In addition, a method is introduced for automatically combining statistically significant alignments produced by BLAST into a position-specific score matrix, and searching the database using this matrix. The resulting Position-Specific Iterated BLAST (PSIBLAST) program runs at approximately the same speed per iteration as gapped BLAST, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily.

Analyzing real-time PCR data by the comparative C(T) method.

Abstract: Two different methods of presenting quantitative gene expression exist: absolute and relative quantification. Absolute quantification calculates the copy number of the gene usually by relating the PCR signal to a standard curve. Relative gene expression presents the data of the gene of interest relative to some calibrator or internal control gene. A widely used method to present relative gene expression is the comparative C(T) method also referred to as the 2 (-DeltaDeltaC(T)) method. This protocol provides an overview of the comparative C(T) method for quantitative gene expression studies. Also presented here are various examples to present quantitative gene expression data using this method.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。