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.

Croce, Carlo M.; Huebner, Kay; Isobe, Masaharu; Fainstain, Elena; Lifshitz, Batia; Shtivelman, Emma; Canaani, Eli

doi:10.1073/pnas.84.20.7174

Cited by 54 publications

(29 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 22q11 region contains a large number of highly repetitive as well as intermediate repetitive sequences (10,13,14). There also is evidence that several genes may be duplicated in the region (15,57). The regions in which we have mapped the evolutionary breakpoints of human chromosome 22q11 correspond to regions containing these repetitive sequences.…”

Section: Discussionmentioning

confidence: 99%

Comparative mapping of the human 22q11 chromosomal region and the orthologous region in mice reveals complex changes in gene organization

Puech

Saint-Jore

Funke

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The region of human chromosome 22q11 is prone to rearrangements. The resulting chromosomal abnormalities are involved in Velo-cardio-facial and DiGeorge syndromes (VCFS and DGS) (deletions), ''cat eye'' syndrome (duplications), and certain types of tumors (translocations). As a prelude to the development of mouse models for VCFS͞DGS by generating targeted deletions in the mouse genome, we examined the organization of genes from human chromosome 22q11 in the mouse. Using genetic linkage analysis and detailed physical mapping, we show that genes from a relatively small region of human 22q11 are distributed on three mouse chromosomes (MMU6, MMU10, and MMU16). Furthermore, although the region corresponding to about 2.5 megabases of the VCFS͞DGS critical region is located on mouse chromosome 16, the relative organization of the region is quite different from that in humans. Our results show that the instability of the 22q11 region is not restricted to humans but may have been present throughout evolution. The results also underscore the importance of detailed comparative mapping of genes in mice and humans as a prerequisite for the development of mouse models of human diseases involving chromosomal rearrangements.

show abstract

Section: Discussionmentioning

confidence: 99%

Comparative mapping of the human 22q11 chromosomal region and the orthologous region in mice reveals complex changes in gene organization

Puech

Saint-Jore

Funke

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Thus, the developmental increase in n-chimerin mRNA can be attributed to al mRNA. In the cerebellum, ca2-chimerin mRNA decreased after day 15 (Fig. 3C).…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, as with n-chimerin, 5' heterogeneity in the abl gene is n-chim * generated by alternate splicing of 5' exons transcribed from two promoters (67). The presence of a bcr-related gene, abr, on chromosome 17p (29) and of several 3' bcr gene sequences on chromosome 22 (15,28) implies that gene duplication may have played a role in the evolution of this GAP gene family (as well as of n-and ,B-chimerin genes).…”

Section: A1 2 3 4 56mentioning

confidence: 99%

Alpha 2-chimerin, an SH2-containing GTPase-activating protein for the ras-related protein p21rac derived by alternate splicing of the human n-chimerin gene, is selectively expressed in brain regions and testes.

Hall¹,

Sin²,

Teo³

et al. 1993

Mol. Cell. Biol.

View full text Add to dashboard Cite

n-Chimerin (al-chimerin) is a brain GTPase-activating protein (GAP) for the ras-related p2l'. We now report the occurrence of another form of chimerin, termed a2-chimerin. This is the product of an alternately spliced transcript of the human n-chimerin gene encoding an N-terminal SH2 (src homology 2) domain in addition to the phorbol ester receptor and GAP domains. ad-and ca2-chimerin mRNAs were expressed differently. In the rat brain, only ael-chimerin mRNA was expressed in cerebellar Purkinje cells, although both al-and a2-chimerin mRNAs occurred in neurons in the cerebral cortex, hippocampus, and thalamus. Only ca2-chimerin RNA was expressed in rat testes, in early pachytene spermatocytes. A 45-kDa SH2-containing chimerin corresponding to the a2 form was purified from rat brain. As with Escherichia coli 45-kDa recombinant cv2-chimerin, purified brain ca2-chimerin exhibited racGAP activity which was stimulated by phosphatidylserine. The recombinant SH2 domain bound several 32P-labelled phosphoproteins of PC12 cells, whose phosphorylation increased in response to trophic factors, including nerve growth factor. To examine the relationships of cl-and at2-chimerin transcripts, human genomic DNA clones were characterized. In a2-chimerin mRNA, a 3' splice acceptor site within exon 1 of acl-chimerin mRNA was used, replacing its 5' untranslated region and N-terminal coding sequence. The single human n-chimerin gene was mapped to chromosome 2q31-q32.1, colocalizing with the CRE-BP1 transcription factor gene (2q32). It contained several splice junctions conserved with the sequence-related protein kinase C and ber genes. af2-Chimerin is only the second SH2-containing GAP and the first example of an SH2 domain generated by alternate splicing.The ras superfamily of GTP-binding proteins has diverse functions in cell growth, differentiation, and secretion. These proteins bind GTP and are down-regulated by GTPase-activating proteins (GAPs), which stimulate their intrinsic GTPase activity (8). n-Chimerin is one of a new family of GAPs which regulate members of the rho subfamily (16,24,25), which is involved in cytoskeletal organization (23). rho and rac play a role in the formation of actin stress fibers and focal contacts and in membrane ruffling in response to growth factors (60, 61).n-Chimerin, Bcr, rhoGAP (16), and the rasGAP-associated protein p190 (66) . p190 is a GAP for rho, rac, and cdc42Hs (65). In contrast, n-chimerin acts selectively on rac and is restricted to neurons (40,42). It is enriched in brain regions involved in learning and memory and may have a specialized rac-mediated role in neuronal signalling. A second chimerin, 3-chimerin, is restricted to spermatocytes in late stages of maturation (36). The cysteine-rich phorbol ester-binding and GAP sequences are conserved in 1-chimerin (97 and 72% amino acid identity, respectively) (36). Both domains are present in the putative product of the Drosophila rotund gene, which is expressed in imaginal discs and the developing testis (1). rasGAP both regulates GTPase...

show abstract

“…This region is surrounded by the coding exons of a gene of unknown function, also called BCR (19,20). BCR is one member of a family of four closely related genes distributed along chromosome 22 (9). The breakpoints found on chromosome 9 are more widely distributed, but all fall upstream of a specific exon of the ABL oncogene, known as the common acceptor exon or exon 2 (1,2).…”

mentioning

confidence: 99%

Alternative forms of the BCR-ABL oncogene have quantitatively different potencies for stimulation of immature lymphoid cells.

1989

View full text Add to dashboard Cite

The Philadelphia chromosome (t9:22;q34:qll) is found in more than 90% of patients with chronic myelogenous leukemia, in 10 to 20% of patients with acute lymphocytic leukemia, and in 1 to 2% of patients with acute myelogenous leukemia. Alternative chimeric oncogenes are formed by splicing different sets of BCR gene exons on chromosome 22 across the translocation breakpoint to a common set ofABL oncogene sequences on chromosome 9. This results in an 8.7-kilobase mRNA that encodes the P210 BCR-ABL gene product commonly found in patients with chronic myelogenous leukemia or a 7.0-kilobase mRNA that produces the P185 BCR-ABL gene product found in most Philadeliphia chromosome-positive patients with acute lymphocytic leukemia. To compare the efficiency of growth stimulation by these two proteins, we derived cDNA clones for each with identical 5' and 3' untranslated regions and expressed them from retrovirus vectors. Matched stocks were compared for potency to transform immature B-lymphoid lineage precursors. The growth-stimulating effects of P185 for this cell type were found to be significantly greater than those of P210. Structural changes in BCR may regulate the effectiveness of the ABL tyrosine kinase function, as monitored by lymphocyte growth response. Changes in mitogenic potency may help to explain the more acute leukemic presentation usually associated with expression of the P185 BCR-ABL oncogene.

show abstract

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.

Cited by 54 publications

References 28 publications

Comparative mapping of the human 22q11 chromosomal region and the orthologous region in mice reveals complex changes in gene organization

Comparative mapping of the human 22q11 chromosomal region and the orthologous region in mice reveals complex changes in gene organization

Alpha 2-chimerin, an SH2-containing GTPase-activating protein for the ras-related protein p21rac derived by alternate splicing of the human n-chimerin gene, is selectively expressed in brain regions and testes.

Alternative forms of the BCR-ABL oncogene have quantitatively different potencies for stimulation of immature lymphoid cells.

Contact Info

Product

Resources

About