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C M Croce

Publications and source records attributed to C M Croce.

At least 343 records · Page 19Linked to original sources
PubMed1986

Molecular genetics of B- and T-cell neoplasia.

Specific chromosomal translocations are involved in more than 80% of human B-cell neoplasms. In all these cases the neoplastic phenotype is apparently the consequence of reciprocal chromosomal translocations involving the loci for human immunoglobulin (Ig) chains and either well described cellular proto-oncogenes or putative proto-oncogenes. The juxtaposition of the proto-oncogenes to the Ig loci results in their transcriptional deregulation, because of their proximity to genetic elements within the Ig loci capable of activating gene transcription in cis over considerable chromosomal distances. Sequence analysis of the translocation breakpoints has provided important insights concerning the molecular mechanisms involved in chromosome translocation in B-cells. It appears that the reciprocal translocations contributing to B-cell neoplasia are catalyzed by the same enzymes that are involved in physiological Ig gene rearrangements. The analysis of human B-cell leukemias and lymphomas has also provided considerable information concerning the possible scenarios for B-cell neoplastic transformation. It is clear that the Epstein-Barr virus does not play a direct role in neoplastic transformation, but it may contribute by increasing the number of B-cells at risk of developing chromosome translocations during Ig gene rearrangements. Cytogenetic and molecular genetic analysis of T-cell malignancies is beginning to provide a very similar scenario for neoplastic transformation. The locus for the alpha chain of the T-cell receptor is directly involved, and it apparently juxtaposes to proto-oncogenes or to putative proto-oncogenes leading to their transcriptional deregulation. It seems quite likely that the enzyme system involved in rearrangements of the genes for the T-cell receptor plays a crucial role in the causation of these chromosomal translocations. Thus, the genetic basis of many human B- and T-cell neoplasms may be quite similar. For the future, the challenge resides in trying to characterize specifically the role of both old and new proto-oncogenes in B- and T-cell proliferation, normal and neoplastic.

B-Lymphocytes↗
PubMed1985

The human gene encoding GM-CSF is at 5q21-q32, the chromosome region deleted in the 5q- anomaly.

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) is a 22,000-dalton glycoprotein that stimulates the growth of myeloid progenitor cells and acts directly on mature neutrophils. A full-length complementary DNA clone encoding human GM-CSF was used as a probe to screen a human genomic library and isolate the gene encoding human GM-CSF. The human GM-CSF gene is approximately 2.5 kilobase pairs in length with at least three intervening sequences. The GM-CSF gene was localized by somatic cell hybrid analysis and in situ hybridization to human chromosome region 5q21-5q32, which is involved in interstitial deletions in the 5q- syndrome and acute myelogenous leukemia. An established, human promyelocytic leukemia cell line, HL60, contains a rearranged, partially deleted GM-CSF allele and a candidate 5q- marker chromosome, indicating that the truncated GM-CSF allele may reside at the rejoining point for the interstitial deletion on the HL60 marker chromosome.

Anemia↗
PubMed1985

The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining.

In this study, the joining sequences between chromosomes 14 and 18 on the 14q+ chromosomes of a patient with pre-B-cell leukemia and four patients with follicular lymphoma carrying a t(14;18) chromosome translocation were analyzed. In each case, the involved segment of chromosome 18 has recombined with the immunoglobulin heavy-chain joining segment (JH) on chromosome 14. The sites of the recombination on chromosome 14 are located close to the 5' end of the involved JH segment, where the diversity (D) regions are rearranged with the JH segments in the production of active heavy-chain genes. As extraneous nucleotides (N regions) were observed at joining sites and specific signal-like sequences were detected on chromosome 18 in close proximity to the breakpoints, it is concluded that the t(14;18) chromosome translocation is the result of a mistake during the process of VDJ joining at the pre-B-cell stage of differentiation. The putative recombinase joins separated DNA segments on two different chromosomes instead of joining separated segments on the same chromosome, causing a t(14;18) chromosome translocation in the involved B cells.

B-Lymphocytes↗
PubMed1985

Locus of the alpha-chain of the T-cell receptor is split by chromosome translocation in T-cell leukemias.

Mouse lymphoma cells were hybridized with two human acute T-cell leukemias with a t(11;14) (p13;q11) translocation and the segregated hybrids were examined for the presence of the DNA segments coding for the constant (C) and the variable (V) regions of the alpha chain (C alpha and V alpha) of the T-cell receptor. The C alpha segment was translocated to the involved chromosome 11 (11p+) while the V alpha segment remained on the involved chromosome 14 (14q-). The data indicate that the locus for the alpha chain of the T-cell receptor is split by the chromosomal breakpoint between the V alpha and the C alpha gene segments, and that the V alpha segments are proximal to the C alpha segment within chromosome band 14q11.2.

Animals↗
PubMed1985

Specific immunoglobulin production and enhanced tumorigenicity following ascites growth of human hybridomas.

Human X human hybridomas constructed with the B6 lymphoblastoid clone, which produces antitetanus toxoid (TT) antibody, and the lymphoblastoid cell line KR-4 or human hybrid myeloma KR-12, were adapted to growth as ascites in pristane-treated BALB/c nude mice by a single prior passage as a solid subcutaneous (s.c.) tumor in irradiated nude mice followed by in vitro culture. Both B6 X KR-4 and B6 X KR-12 hybrids produced anti-TT antibody and phenotypically resembled the lymphoblastoid KR-4, or the hybrid myeloma KR-12 parent, respectively. Growth as ascites increased the tumorigenicity of both hybrids in nude mice as measured by tumor incidence and rate of tumor growth. The observed increase in tumorigenicity of these hybrid cells after ascites growth was associated with a substantial loss of chromosomes. Passage of the B6 X KR-4 lymphoblastoid hybrid resulted in several reversible morphological changes characteristic of myeloma cells. These changes correlated with increased human Ig production. These observations provide a system for greatly amplifying human monoclonal antibody production.

Animals↗
PubMed1985

Cloning and sequencing of a rearranged V lambda gene from a Burkitt's lymphoma cell line expressing kappa light chains.

We have cloned and sequenced a rearranged V lambda gene from a Burkitt's lymphoma cell line PA682(PB). This cell line has two rearranged kappa loci and has been shown to be expressing kappa light chains. This V lambda gene has been identified as a member of the V lambda subgroup III gene family based on the homology of the predicted amino acid sequence of PAV lambda with the reported sequences of the V lambda protein DEL of subgroup III. Nine cross-hybridizing bands have been detected on Southern blots and the chromosomal orientation of the V lambda subgroup III gene family has been determined in relation to the V lambda subgroup I gene family. Although the PAV lambda rearrangement has occurred via a legitimate V-J joining and a normal size transcript is detected on Northern blots, the nucleotide sequence reveals a high level of mutations resulting in multiple termination signals within the V gene coding sequence and only a truncated V lambda protein can be translated. This confirms previous observations that although multiple light chain genes may be transcribed, only one functional light chain protein can be synthesized.

Base Sequence↗
PubMed1985

Involvement of the bcl-2 gene in human follicular lymphoma.

Recombinant DNA probes were cloned for the areas flanking the breakpoint on chromosome 18 in cells from a patient with acute lymphocytic leukemia of the B-cell type; cells of this line carry the t(14;18) chromosomal translocation. Two of the probes detected DNA rearrangements in approximately 60 percent of the cases of follicular lymphoma screened. In follicular lymphoma, most of the breakpoints in band q21 of chromosome 18 were clustered within a short stretch of DNA, approximately 2.1 kilobases in length. Chromosome 18-specific DNA probes for the areas flanking the breakpoints also detected RNA transcripts 6 kilobases in length in various cell types. The gene coding for these transcript (the bcl-2 gene) seems to be interrupted in most cases of follicular lymphomas carrying the t(14;18) chromosomal translocation.

B-Lymphocytes↗
PubMed1985

Location of gene for beta subunit of human T-cell receptor at band 7q35, a region prone to rearrangements in T cells.

The T-cell receptor is formed by two chains, alpha and beta, for which specific clones were recently obtained. In this report the gene for the beta chain of the human T-cell receptor was located on the long arm of chromosome 7, band q35, by means of in situ hybridization. This chromosome region in T cells is unusually prone to develop breaks in vivo, perhaps reflecting instability generated by somatic rearrangement of T-cell receptor genes during normal differentiation in this cell lineage.

Adult↗
PubMed1985

Coexpression of translocated and normal c-myc oncogenes in hybrids between Daudi and lymphoblastoid cells.

Mechanisms that affect the transcription of the c-myc oncogene take part in the development of B-cell neoplasias such as Burkitt's lymphoma. Daudi Burkitt lymphoma cells, which express only the translocated c-myc oncogene, were hybridized with human lymphoblastoid cells, which express the normal c-myc gene; the hybrids were phenotypically lymphoblastoid and expressed both the translocated and the normal c-myc gene. This result contrasts with the findings that the decapitated c-myc gene, translocated to an immunoglobulin switch mu or alpha region, is transcriptionally silent in lymphoblastoid hybrids. Thus, there may be at least two distinct enhancer-like elements capable of deregulating c-myc transcription in lymphomas and leukemias with t(8;14) chromosome translocations. In addition, since the Daudi X lymphoblastoid hybrids express both the translocated and the normal c-myc gene, the c-myc gene product does not autoregulate c-myc transcription.

Burkitt Lymphoma↗
PubMed1985

Gene for alpha-chain of human T-cell receptor: location on chromosome 14 region involved in T-cell neoplasms.

A human complementary DNA clone specific for the alpha-chain of the T-cell receptor and a panel of rodent X human somatic cell hybrids were used to map the alpha-chain gene to human chromosome 14 in a region proximal to the immunoglobulin heavy chain locus. Analysis by means of in situ hybridization of human metaphase chromosomes served to further localize the alpha-chain gene to region 14q11q12, which is consistently involved in translocations and inversions detectable in human T-cell leukemias and lymphomas. Thus, the locus for the alpha-chain T-cell receptor may participate in oncogene activation in T-cell tumors.

Animals↗
PubMed1985

Chromosomal orientation of the lambda light chain locus: V lambda is proximal to C lambda in 22q11.

We have demonstrated that the chromosomal breakpoint at 22q11 of a Burkitt lymphoma cell line (PA682) with an 8;22 translocation interrupts the variable region of the lambda light chain locus. In these cells, all of the C lambda and some V lambda sequences translocate to the 8q+ chromosome whereas some V lambda sequences remain on the 22q-. These results indicate that the lambda light chain locus on the long arm of chromosome 22 is oriented such that V lambda is proximal to C lambda.

Burkitt Lymphoma↗