Biomedical subjects

S M Benjes

Publications and source records attributed to S M Benjes.

7 recordsLinked to original sources

PubMed2001

A full-length and potentially active LINE element is integrated polymorphically within the IGL locus in a genomically unstable region of chromosome 22.

Leukemic cells of a patient diagnosed with chronic myeloid leukemia (CML) showed a complex BCR-ABL1 rearrangement hidden within a normal appearing karyotype. Previous molecular studies had established that the 3' BCR had recombined at a novel site within the variable region of the immunoglobulin lambda locus ( IGL). A segment of DNA mapping very close to the site of the IGL/3' BCR recombination recognized a previously undescribed insertion polymorphism. A combination of molecular hybridization studies and long-range polymerase chain reaction was used to isolate a 6-kb full-length long interspersed nuclear element (LINE or L1), here designated L1(IGL), which occupies 19% of alleles in the general population. Although unclonable, DNA sequence analysis by a primer walking approach established that L1(IGL) has features characteristic of an actively retrotransposing element. The L1(IGL) element has a 5' untranslated region, two open reading frames (ORF-1 and ORF-2), a 3' untranslated region and terminates in a poly-A tail. We compared the DNA sequence and the predicted amino acid sequence of L1(IGL) with a consensus sequence compiled from seven reported active L1 elements. This analysis indicated that L1(IGL) has high potential for involvement in as yet undetermined somatically and constitutionally acquired disease, not only through recombination mechanisms, but also through retrotransposition events. This full-length L1 element maps close within the IGLlocus to L1.2, one of only nine active L1 elements that have been reported so far. L1(IGL) and L1.2 map within a wider and well-recognized region of genomic instability on chromosome 22.

Base Sequence↗

PubMed1999

3' BCR recombines with IGL locus in BCR-ABL-positive philadelphia-negative chronic myeloid leukemia.

We have isolated the 3' BCR breakpoint junction of a complex BCR-ABL1 rearrangement found in leukemic cells with a cytogenetically normal karyotype, and the corresponding germline fragment that spanned the 3' BCR recombination site. Fluorescence in situ hybridization localized the 3' BCR recombination site to 22q11, about 350-600 kb proximal to BCR. Restriction map and DNA sequence comparisons indicated that 3' M-Bcr had recombined at a site within the variable region (Itv Region IV) of the immunoglobulin lambda (IGL) locus. Somatic rearrangement of DNA sequences (variable, joining, and constant regions) within the IGL locus, as in other Ig and TCR loci, represents the basis for human antibody diversity. Misrecombination of these somatically rearranging sites has been associated with chromosomal rearrangements in lymphoid leukemia and lymphoma, but there are no previous descriptions of IGL involvement in genomic aberrations associated with myeloid leukemia. Genes Chromosomes Cancer 26:366-371, 1999.

3' Untranslated Regions↗

PubMed1998

The BCR gene recombines preferentially with Alu elements in complex BCR-ABL translocations of chronic myeloid leukaemia.

Chronic myeloid leukaemia (CML) develops when two genes, BCR on chromosome 22 and ABL on chromosome 9, recombine to form a hybrid BCR-ABL gene with leukaemogenic properties. The mechanism which underlies this recombination is unknown, but additional chromosome sites may be involved to form complex BCR-ABL rearrangements. The majority of breakpoints in BCR occur within a 5 kb major breakpoint cluster region, M-Bcr. Here, we show that the 3' part of M-Bcr recombined within, or immediately adjacent to, Alu elements at the additional sites in all five complex BCR-ABL rearrangements that have been examined so far. This is a new finding which suggests that Alu sequences have an affinity for the BCR-ABL recombination process in complex rearrangements, and provides additional evidence for the association of these elements with somatic rearrangements which cause human leukaemia. We further show that sequence motifs similar to IgH switch pentamers and consensus binding sites of the lymphoid-associated Translin protein are present on one or more participating strands at 3'M-Bcr recombination sites. Motifs similar to Translin-binding sites were also identified within the Alu consensus. Expressed sequences mapped close to the breakpoint sites on other chromosomes in three of the five cases examined.

Base Sequence↗

PubMed1995

Deletion 20q in association with Philadelphia chromosome positive acute lymphoblastic leukemia. A report of two cases.

Cytogenetic deletions involving the long arm of chromosome 20 are thought to be characteristic of myeloid disorders. We report clinical and cytogenetic observations of two adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia: one with a smaller 20q deletion that was the sole cytogenetic abnormality in a persisting remission clone, the other with a larger 20q deletion that was a late addition to the leukemic clone at disease relapse following allogeneic bone marrow transplantation.

Adolescent↗

PubMed1993

Oligoclonal B-cell leukemia characterized by spontaneous cell division and telomere association.

Cytogenetic analysis of unstimulated cultures from a female patient with chronic B-cell leukemia (CLL) revealed three cytogenetically distinct clones, suggesting that the patient's leukemia was oligoclonal. Immunoglobulin heavy chain gene rearrangement studies revealed 1 germline and 4 rearranged bands, indicative of an oligoclonal leukemic population. Further evidence of oligoclonality was provided by X-linked RFLP studies. This is the first report of oligoclonality in CLL demonstrated by cytogenetic, immunoglobulin gene rearrangement, and X-chromosome inactivation studies. In addition to oligoclonality, the patient's leukemic cells exhibited telomere association, a Robertsonian translocation, and clonal evolution, suggesting an underlying genomic instability.

Cell Division↗

PubMed1991

Molecular definition of interstitial deletions of chromosome 13 in leukemic cells.

Three patients with leukemia and one with a myeloproliferative disorder carried an interstitial deletion of chromosome 13, del(13)(q12q14), in leukemic cells. Proximal and distal breakpoints of the deleted segment were characterized by using DNA restriction fragment length polymorphisms of chromosome 13 supplemented by quantitative densitometry of hybridization signals to determine the copy number of individual loci. Both proximal and distal breakpoints varied between patients, and it is unlikely that a significant hybrid gene was formed by rejoining at the breakpoint junctions. The retinoblastoma gene was encompassed by the deleted segment in all four patients.

Aged↗

PubMed1991

Complex karyotypic evolution in B-cell chronic lymphocytic leukemia.

Cytogenetic analysis at diagnosis in a female patient with chronic B-cell leukemia showed a single abnormal clone with a 4p+ abnormality, 46,XX, -4, +der(4)t(4;?)(p16;?). Six additional clones evolved from this clone during the following 4 1/2 years and showed 3p+, 4p-, and 11q- chromosomes in addition to the 4p+ abnormality. Immunoglobulin heavy chain gene rearrangement studies showed two rearranged bands and a faint germline band. Following splenectomy, a strong germline and faint rearranged bands were seen, suggesting that the majority of cells were normal, whereas cytogenetic studies showed that the karyotypically abnormal cells were still present. The combination of cytogenetic and Ig gene rearrangement studies provides detailed information regarding the number of circulating normal and leukemic cells.

Chromosome Aberrations↗