Author
Carlo M. Croce
Other affiliations: University of Nebraska Medical Center, University of California, Los Angeles, Thomas Jefferson University ...read more
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.
Topics: microRNA, Cancer, Chronic lymphocytic leukemia, Gene, Leukemia
Papers published on a yearly basis
Papers
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TL;DR: Analysis of data from a large tumor lymphoma data bank including 194 cases of lymphoproliferative disorders of B- and T-cell origin as well as reactive lymphoid tissues indicates that TCL1 is expressed in more differentiated B cells, under both reactive and neoplastic conditions, from antigen committed B cells and in germinal center B cell cells and is down-regulated in the latest stage ofB-cell differentiation.
Abstract: Chromosomal rearrangements observed in T-cell prolymphocytic leukemia involve the translocation of one T-cell receptor gene to either chromosome 14q32 or Xq28, deregulating the expression of cellular protooncogenes of unknown function, such as TCL1 or its homologue, MTCP1. In the human hematopoietic system, TCL1 expression is predominantly observed in developing B lymphocytes, whereas its overexpression in T cells causes mature T-cell proliferation in transgenic mice. In this study, using a newly generated monoclonal antibody against recombinant TCL1 protein, we extended our analysis mainly by immunohistochemistry and also by fluorescence-activated cell sorting and Western blot to a large tumor lymphoma data bank including 194 cases of lymphoproliferative disorders of B- and T-cell origin as well as reactive lymphoid tissues. The results obtained show that in reactive lymphoid tissues, TCL1 is strongly expressed by a subset of mantle zone B lymphocytes and is expressed to a lesser extent by follicle center cells and by scattered interfollicular small lymphocytes. In B-cell neoplasia, TCL1 was expressed in the majority of the cases, including lymphoblastic lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, follicular lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma (60%), and primary cutaneous B cell lymphoma (55%). TCL1 expression was observed in both the cytoplasmic and nuclear compartments, as confirmed by Western blot analysis. Conversely, TCL1 was not expressed in Hodgkin/Reed-Sternberg cells, multiple myelomas, marginal zone B-cell lymphomas, CD30+ anaplastic large cell lymphoma, lymphoblastic T-cell lymphoma, peripheral T-cell lymphoma, and mycosis fungoides. These data indicate that TCL1 is expressed in more differentiated B cells, under both reactive and neoplastic conditions, from antigen committed B cells and in germinal center B cells and is down-regulated in the latest stage of B-cell differentiation.
121 citations
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TL;DR: The data support a novel leukemogenic mechanism in AML where PRMT5 mediates both silencing and transcription of genes that participate in a ‘yin-yang’ functional network supporting leukemia growth.
Abstract: Changes in the enzymatic activity of protein arginine methyltransferase (PRMT) 5 have been associated with cancer; however, the protein's role in acute myeloid leukemia (AML) has not been fully evaluated. Here, we show that increased PRMT5 activity enhanced AML growth in vitro and in vivo while PRMT5 downregulation reduced it. In AML cells, PRMT5 interacted with Sp1 in a transcription repressor complex and silenced miR-29b preferentially via dimethylation of histone 4 arginine residue H4R3. As Sp1 is also a bona fide target of miR-29b, the miR silencing resulted in increased Sp1. This event in turn led to transcription activation of FLT3, a gene that encodes a receptor tyrosine kinase. Inhibition of PRMT5 via sh/siRNA or a first-in-class small-molecule inhibitor (HLCL-61) resulted in significantly increased expression of miR-29b and consequent suppression of Sp1 and FLT3 in AML cells. As a result, significant antileukemic activity was achieved. Collectively, our data support a novel leukemogenic mechanism in AML where PRMT5 mediates both silencing and transcription of genes that participate in a 'yin-yang' functional network supporting leukemia growth. As FLT3 is often mutated in AML and pharmacologic inhibition of PRMT5 appears feasible, the PRMT5-miR-29b-FLT3 network should be further explored as a novel therapeutic target for AML.
121 citations
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TL;DR: The utility of this animal model of CLL is demonstrated and it is defined as a versatile model to investigate both the molecular mechanisms of cancer-induced immune suppression and immunotherapeutic repair strategies.
Abstract: Preclinical animal models have largely ignored the immune-suppressive mechanisms that are important in human cancers. The identification and use of such models should allow better predictions of successful human responses to immunotherapy. As a model for changes induced in nonmalignant cells by cancer, we examined T-cell function in the chronic lymphocytic leukemia (CLL) Eμ-TCL1 transgenic mouse model. With development of leukemia, Eμ-TCL1 transgenic mice developed functional T-cell defects and alteration of gene and protein expression closely resembling changes seen in CLL human patients. Furthermore, infusion of CLL cells into young Eμ-TCL1 mice induced defects comparable to those seen in mice with developed leukemia, demonstrating a causal relationship between leukemia and the T-cell defects. Altered pathways involved genes regulating actin remodeling, and T cells exhibited dysfunctional immunological synapse formation and T-cell signaling, which was reversed by the immunomodulatory drug lenalidomide. These results further demonstrate the utility of this animal model of CLL and define a versatile model to investigate both the molecular mechanisms of cancer-induced immune suppression and immunotherapeutic repair strategies.
120 citations
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TL;DR: The recent findings in the molecular biology of FHIT are described with particular focus on the opportunities for treatment and prevention of cancer that have emerged.
Abstract: Chromosomal abnormalities, including homozygous deletions and loss of heterozygosity, are among the most common features of human tumours. The short arm of human chromosome 3, particularly the region 3p14.2, is a major site of such rearrangements. The 3p14.2 region spans the most active common fragile site of the human genome, encompassing a familial-kidney-cancer-associated breakpoint and a papilloma virus integration site. 6 years ago, the FHIT gene was identified in this region. Subsequent studies have shown that FHIT is commonly the target of chromosomal aberrations involving the long arm of human chromosome 3 and is thereby inactivated in most of the common human malignant diseases, including cancers of the lung, oesophagus, stomach, breast, and kidney. During the past 5 years, evidence has accumulated in support of a tumour-suppressor function for FHIT. In this review, we describe the recent findings in the molecular biology of FHIT with particular focus on the opportunities for treatment and prevention of cancer that have emerged.
120 citations
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TL;DR: The chromosomal mapping of two kinases, cdk3 and PISSLRE and PITALRE, the cdc2-related kinases recently cloned by us, map to regions previously shown to exhibit loss of heterozygosity in breast and other tumors.
Abstract: Orderly progression through the cell cycle requires sequential activation and inactivation of cyclin-dependent kinases (cdks). This is achieved in part through the association of cdks with positive regulators called cyclins and inactivation of cyclin-cdk complexes by a rapidly growing number of cyclin-cdk inhibitors. Recently, the role of cell cycle control proteins both as primary effectors and as mediators of tumorigenesis has become a subject of increased interest. Here we report the chromosomal mapping of two cdks, cdk3 and cdk6, two putative cdks, PISSLRE and PITALRE, and one cyclin-dependent kinase inhibitor, p27, to chromosomal regions which may be altered in human tumors and examine their possible involvement in some of these malignancies. In particular, two of the kinases, cdk3 and PISSLRE and PITALRE, the cdc2-related kinases recently cloned by us, map to regions previously shown to exhibit loss of heterozygosity in breast and other tumors.
120 citations
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TL;DR: 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.
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.
70,111 citations
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TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
51,099 citations
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TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
32,946 citations
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TL;DR: This protocol provides an overview of the comparative CT method for quantitative gene expression studies and various examples to present quantitative gene Expression data using this 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.
20,580 citations
28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组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�ly.
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。
18,940 citations