Evidence for the Involvement of
            <i>GM-CSF</i>
            and
            <i>FMS</i>
            in the Deletion (5q) in Myeloid Disorders

Beau, MM Le; Westbrook, CA; Diaz, MO; Larson, Richard A.; Rowley, JD; Gasson, JC; Golde, DW; Sherr, CJ

doi:10.1126/science.3484837

Cited by 226 publications

(65 citation statements)

References 44 publications

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“…Three other cloned genes have been mapped to the distal long arm of chromosome 5. The gene encoding granulocytemacrophage colony-stimulating factor (GM-CSF) is at 5q23-q31, probably proximal to the genes for the /2AR and the PDGF receptor (30). The protooncogene FMS, a gene whose product is related to or identical to the receptor for macrophage colony-stimulating factor (CSF-1), is located at 5q33 or q34, distal to the genes for the P2AR and the PDGF receptor (30), and CSF-1 is at 5q33.1 (31).…”

Section: Resultsmentioning

confidence: 99%

cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor.

Kobilka¹,

Dixon²,

Frielle³

et al. 1987

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

606

184

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We have isolated and sequenced a cDNA encoding the human 132-adrenergic receptor. The deduced amino acid sequence (413 residues) is that of a protein containing seven clusters of hydrophobic amino acids suggestive of membrane-spanning domains. While the protein is 87% identical overall with the previously cloned hamster P2-adrenergic receptor, the most highly conserved regions are the putative transmembrane helices (95% identical) and cytoplasmic loops (93% identical), suggesting that these regions of the molecule harbor important functional domains. Several of the transmembrane helices also share lesser degrees of identity with comparable regions of select members of the opsin family of visual pigments. We have localized the gene for the P2-adrenergic receptor to q31-q32 on chromosome 5. This is the same position recently determined for the gene encoding the receptor for platelet-derived growth factor and is adjacent to that for the FMS protooncogene, which encodes the receptor for the macrophage colony-stimulating factor.Many hormones, neurotransmitters, and drugs influence cellular metabolic activities by stimulating the adenylate cyclase system, leading to the generation of the second messenger cAMP and activation of the cAMP-dependent protein kinase. The molecular components of this plasma membrane signaling system include specific receptors that bind ligands, the catalyst that converts ATP to cAMP, and guanine nucleotide regulatory or G proteins that functionally couple the receptors to the enzyme (1). The latter two components of the system have been purified and genes encoding several members of the "G protein family" have been cloned.Of the receptors that are coupled to adenylate cyclase the only one that has been characterized in any detail is the p-adrenergic receptor (,8AR). Two pharmacologically and physiologically distinct subtypes of this receptor, termed ,31AR and f32AR, are both membrane glycoproteins of Mr 64,000 (2). Very recently, we reported cloning of cDNA and the gene for the hamster f32AR (3). The deduced protein sequence indicated a protein of 418 amino acids, with seven clusters of hydrophobic amino acids likely representing membrane-spanning regions. This topology resembles that of the visual "light receptor" rhodopsin, which also possesses seven membrane-spanning domains (4-6).We now report the cloning and complete nucleotide sequence of the cDNA for the human ,82AR. While the receptor is highly similar to its hamster counterpart (87% of the amino acid residues are identical), significant regional differences in the extent of identity are noted. METHODScDNA Library Screening. The human placenta cDNA library was kindly provided by Evan Sadler (Washington University School of Medicine). The cDNA was prepared from term placenta poly(A)+ RNA and cloned in phage Xgtll. The library contains 5 x 106 independent recombinants. The A431 Xgtll library was prepared from poly(A)+ RNA from actively dividing A431 cells by methods previously described (3). It contains 1 x 106 independent reco...

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Section: Resultsmentioning

confidence: 99%

cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor.

Kobilka¹,

Dixon²,

Frielle³

et al. 1987

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

606

184

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“…6 However, GM-CSF also facilitates cell differentiation and maturation, which are usually blocked in AML. Finally, partial and complete deletion of the GM-CSF gene, including deletion of 5q31, occurs in chromosomal abnormalities, which are associated with secondary AML and myelodysplastic syndrome (MDS), 7 suggesting a complex role of GM-CSF dysregulation in leukemogenesis.…”

Section: Introductionmentioning

confidence: 99%

High titer autoantibodies to GM-CSF in patients with AML, CML and MDS are associated with active disease

et al. 2008

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“…An important series of studies delineated two common deleted regions (CDRs) on 5q. 9,10,[20][21][22] Functional studies, including both the systematic examination of each gene within a CDR and the investigation of specific candidate genes, are now identifying the roles for individual genes in the pathogenesis of MDS.…”

Section: Introductionmentioning

confidence: 99%

Deletion 5q in myelodysplastic syndrome: a paradigm for the study of hemizygous deletions in cancer

Ebert

2009

Leukemia

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Evidence for the Involvement of GM-CSF and FMS in the Deletion (5q) in Myeloid Disorders

Cited by 226 publications

References 44 publications

cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor.

cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor.

High titer autoantibodies to GM-CSF in patients with AML, CML and MDS are associated with active disease

Deletion 5q in myelodysplastic syndrome: a paradigm for the study of hemizygous deletions in cancer

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