Biomedical subjects

B Lifshitz

Publications and source records attributed to B Lifshitz.

5 recordsLinked to original sources

PubMed1988

bcr genes and transcripts.

Human chronic myelogenous leukemia (CML) is a clonal hematologic disorder. CML is characterized by the t(9:22) chromosome translocation which results in translocation of the oncogene abl from chromosome 9 into the breakpoint cluster region (bcr) gene on chromosome 22. We cloned and characterized the cDNA of the normal bcr gene. The bcr gene codes for a protein of 1271 amino acids. The open reading frame is preceded by a region high in GC. At the 5' of this region we identified several GC motifs which are probably involved in the initiation of bcr transcription. bcr transcripts of 7.0 and 4.5 kb are expressed in all cell types examined. These transcripts share all cDNA sequences analysed, including the 5' untranslated region. The latter as well as 902 or 927 amino acids are included within the CML-specific bcr-abl mRNA transcribed from the chimeric bcr-abl gene on chromosome 22. In addition to the complete bcr gene, the human genome contains 3 bcr-related genes containing the last seven exons of the intact bcr gene. One of these genes was analysed in detail and showed high sequence homology with the latter. The three bcr-related genes were probably derived from the intact gene by subsequent steps of duplication.

Base Sequence↗

PubMed1987

Mapping of four distinct BCR-related loci to chromosome region 22q11: order of BCR loci relative to chronic myelogenous leukemia and acute lymphoblastic leukemia breakpoints.

A probe derived from the 3' region of the BCR gene (breakpoint cluster region gene) detects four distinct loci in the human genome. One of the loci corresponds to the complete BCR gene, whereas the others contain a 3' segment of the gene. After HindIII cleavage of human DNA, these four loci are detected as 23-, 19-, 13-, and 9-kilobase-pair fragments, designated BCR4, BCR3, BCR2, and BCR1, respectively, with BCR1 deriving from the original complete BCR gene. All four BCR loci segregate 100% concordantly with human chromosome 22 in a rodent-human somatic cell hybrid panel and are located at chromosome region 22q11.2 by chromosomal in situ hybridization. The BCR2 and BCR4 loci are amplified in leukemia cell line K562 cells, indicating that they fall within the amplification unit that includes immunoglobulin lambda light chain locus (IGL) and ABL locus on the K562 Philadelphia chromosome (Ph1); additionally, in chronic myelogenous leukemia-derived mouse-human hybrids retaining a Ph1 chromosome in the absence of the 9q+ and normal chromosome 22, BCR2 and BCR4 loci are retained, whereas the 3' region of BCR1 and the BCR3 locus are lost, indicating that BCR3 is distal to BCR1 on chromosome 22. Similarly, in mouse-human hybrids retaining a Ph1 chromosome derived from an acute lymphoblastic leukemia-in the absence of the 9q+ and 22, only BCR2 and BCR4 loci are retained, indicating that the breakpoint in this acute lymphoblastic leukemia, as in chronic myelogenous leukemia, is proximal to the BCR1 3' region, but distal to the IGLC locus and the BCR2 and BCR4 3' loci. Thus, the order of loci on chromosome 22 is centromere----BCR2, BCR4, and IGL----BCR1----BCR3----SIS, possibly eliminating BCR2 and BCR4 loci as candidate targets for juxtaposition to the ABL gene in the acute lymphoblastic leukemia Ph1 chromosome.

Chromosome Aberrations↗

PubMed1986

Alternative splicing of RNAs transcribed from the human abl gene and from the bcr-abl fused gene.

The primary structure of normal abl protein was determined by sequencing the coding region of its cDNA. abl contains two alternative 5' exons spliced to a common set of 3' exons to yield the two major abl RNA transcripts. These transcripts initiate in different promoter regions and give rise to proteins that vary in their N-termini. In the human cell line K562, abl is translocated from chromosome 9 to within the bcr gene on chromosome 22. Within the fused bcr-abl gene, abl exon II alternatively splices to two adjacent bcr exons. This phenomenon is seen in many patients with chronic myeloid leukemia.

Abelson murine leukemia virus↗

PubMed1986

Expression of HLA-DR molecules by keratinocytes, and presence of Langerhans cells in the dermal infiltrate of active psoriatic plaques.

Immunoperoxidase staining of skin sections and immunofluorescence analysis of keratinocyte suspensions obtained from suction blisters of psoriatic plaques were performed using an mAb, Josh 524.4.1, and Fab'2 fragments of a rabbit antiserum, both of which are directed against nonpolymorphic determinants of HLA-DR molecules. HLA-DR+ keratinocytes were present in plaques, but not normal-appearing skin, from a significant portion of patients with active psoriasis. Double-labelling immunofluorescence experiments with either the monoclonal or polyclonal anti-HLA-DR antibody, in conjunction with the mAb OKT6, which identifies DR+ Langerhans cells, demonstrated that HLA-DR molecules were present on OKT6- keratinocytes. The dermal infiltrate of psoriatic plaques contained T cells expressing the activation antigens, IL-2 receptor (Tac) and HLA-DR, as well as macrophages and OKT6+ cells. There was little difference in the characteristics of the dermal infiltrate between the lesions with or without HLA-DR+ keratinocytes. OKT6+ presumptive Langerhans cells were also found in the dermal infiltrates of patients with lichen planus, contact dermatitis, spongiotic dermatitis, erythema multiforme, basal and squamous cell carcinoma. Studies of keratinocyte suspensions showed that 7-84% of keratinocytes were HLA-DR+. Flow cytometry experiments showed that keratinocytes at all stages of differentiation were HLA-DR+. However, the stem cell-enriched population contained the highest proportion of HLA-DR+ cells. HLA-DR expression by keratinocytes correlated with disease activity. The expression was reversible with successful medical therapy. HLA-DR+ keratinocytes may activate T cells directly or may present an as yet unknown antigen to T cells. These studies provide further support for the hypothesis that immunological mechanisms play an important role in the pathogenesis of psoriasis.

Dermatitis↗

PubMedDate not supplied

Fused transcript of abl and bcr genes in chronic myelogenous leukaemia.

Human chronic myelogenous leukaemia is characterized by a reciprocal translocation between chromosomes 9 and 22 resulting in an abbreviated form of chromosome 22 and the transfer of the abl cellular oncogene from chromosome 9 into the bcr gene of chromosome 22. Characterization of an 8-kilobase RNA specific to chronic myelogenous leukaemia shows it to be a fused transcript of the two genes. The fused protein that would be produced is probably involved in the malignant process.

Base Sequence↗