Involvement of a human gene related to the
            <i>Drosophila spen</i>
            gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia

Mercher, Thomas; Coniat, Maryvonne Busson‐Le; Monni, Richard; Mauchauffé, M; Nguyen‐Khac, Florence; Gressin, Lætitia; Mugneret, Francine; Leblanc, Thierry; Dastugue, Nicole; Berger, Roland; Bernard, Olivier A.

doi:10.1073/pnas.101001498

Cited by 212 publications

(212 citation statements)

References 29 publications

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“…Although the cytogenetic report did not show a standard karyotype [t(1;22)(p13;q13)] or a complex karyotype (chromosome 1, 22, and other chromosome involved), recent studies suggest that the RBM15-MKL1 (OTT-MAL) fusion transcript which was located on the derivative chromosome 22 and not on the derivative chromosome 1 [7][8][9]. RT-PCR and sequence data support the presence of this abnormal fusion transcript in our patient.…”

Section: Discussionsupporting

confidence: 47%

“…Recently, two genes, RBM15 (RNA-binding motif protein-15, also known as OTT (''one twenty-two'')) on chromosome 1 and MKL1 (megakaryocytic leukemia-1, also known as MAL (megakaryocytic acute leukemia)) on chromosome 22, were found to be involved in the translocation [7][8][9]. Both genes possess related sequences in the Drosophila genome with the RBM15 (OTT) gene encoding three RNA-recognition motifs and a spen paralog and ortholog C-terminal domain and the MKL1 (MAL) gene encoding an SAP DNA-binding motif, which is involved in chromatin organization.…”

Section: Introductionmentioning

confidence: 99%

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RBM15-MKL1 (OTT-MAL) fusion transcript in an adult acute myeloid leukemia patient

et al. 2005

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The t(1;22)(p13;q13) is a nonrandom chromosomal abnormality in acute leukemia with the fusion oncogene, RBM15-MKL1 (OTT-MAL), identified recently. However, this abnormality has been described only in infants and young children with acute megakaryoblastic leukemia (AMKL). We report a 59-year-old male patient with the diagnosis of acute myeloid leukemia, subtype M1, who harbors an abnormal chromosome +der(1)t(1;22)(p13;q13). The RBM15-MKL1 (OTT-MAL) fusion transcript was also confirmed by the reverse transcriptase-polymerase chain reaction. This unusual abnormality is rare in adult cases of leukemia, and in children it is restricted to AMKL. This report is accompanied by a review of the literature on the t(1;22)(p13;q13). Am.

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Section: Discussionsupporting

confidence: 47%

Section: Introductionmentioning

confidence: 99%

RBM15-MKL1 (OTT-MAL) fusion transcript in an adult acute myeloid leukemia patient

et al. 2005

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“…[85]. Interestingly, there is a SHARP-like protein in mouse and men, Rbm15/OTT1, that is implicated in acute megakaryoblastic leukemia [86,87] and has been shown to interact with RBP-J, although the RBP-J binding site of SHARP is not conserved in Rbm15/ OTT1 [88]. Rbm15/OTT1 deficient mice are characterized by a loss of peripheral B-cells and an increase in stem-myeloid-and megakaryocyte progenitors [89].…”

Section: Epigenetic Regulation Of Notch Target Genesmentioning

confidence: 99%

The Notch signaling pathway: Transcriptional regulation at Notch target genes

Borggrefe

Oswald

2009

Cell. Mol. Life Sci.

584

499

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. The Notch gene encodes a transmembrane receptor that gave the name to the evolutionary highly conserved Notch signaling cascade. It plays a pivotal role in the regulation of many fundamental cellular processes such as proliferation, stem cell maintenance and differentiation during embryonic and adult development. After specific ligand binding, the intracellular part of the Notch receptor is cleaved off and translocates to the nucleus, where it binds to the transcription factor RBP-J. In the absence of activated Notch, RBP-J represses Notch target genes by recruiting a corepressor complex. Here, we review Notch signaling with a focus on gene regulatory events at Notch target genes. This is of utmost importance to understand Notch signaling since certain RBP-J associated cofactors and particular epigenetic marks determine the specificity of Notch target gene expression in different cell types. We subsequently summarize the current knowledge about Notch target genes and the physiological significance of Notch signaling in development and cancer.

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“…1,2 The phenotype is highly variableover 180 associated clinical manifestations already described -and ranges from severe, with life-threatening malformations, to nearly asymptomatic cases. The major clinical features include congenital heart defects (CHDs), palate defects (velopharyngeal insufficiency, cleft palate, etc), mild-to-moderate immunodeficiency (because of thymic aplasia or hypoplasia), hypocalcemia caused by hypoparathyroidism, a distinct gestalt, developmental delay (DD), learning 1 Département de Génétique, CHU de Reims, Reims, France; 2 Service de Cytogénétique, Hôpital Poissy/Saint-Germain-en-Laye, Poissy, France; 3 Service de Cytogénétique, CHU de Lyon, Lyon, France; 4 CHU Bordeaux, Génétique Médicale, Bordeaux, France; 5 Laboratoire de Cytogénétique, CHU de Marseille, Marseille, France; 6 CHU Nantes, Service de Génétique Médicale, Inserm UMR957, Faculté de Médecine, Nantes, France; 7 Laboratoire de Cytogénétique Pasteur-Cerba, Saint-Ouen l'Aumône, France; 8 Service de Cytogénétique, CHU de Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; 9 Service de Cytogénétique, CHU de Besançon, Besançon, France; 10 Service de Cytogénétique, Biolille, Lille, France; 11 Service de Cytogénétique, Hôpital Saint Vincent de Paul, Paris, France; 12 Laboratoire de Cytogénétique Postnatal, CHU Clemenceau, Caen, France; 13 Service de Cytogénétique et Biologie de la Reproduction, CHRU de Brest, Brest, France; 14 Service de Cytogénétique, CHU de Robert Debré, Paris, France; 15 Service de Cytogénétique, CHU de Strasbourg, Strasbourg, France; 16 Service de Cytogénétique, CHU de Tours, Tours, France; 17 Service de Cytogénétique, CHU de Nancy, Nancy, France; 18 Laboratoire de Cytogénétique Cylab, La Rochelle, France; 19 Service de Cytogénétique, Hôpital de Saint-Denis, Saint-Denis de la Réunion, France; disabilities, intellectual disability (ID) and behavioral disturbances. [3][4][5] Renal, ocular and skeletal anomalies have also been observed.…”

Section: Introductionunclassified

“…Several genes have been implicated in heart malformations, including the major candidate gene TBX1 but also UFD1L, HIRA, CRKL and, most recently, HIC2. [18][19][20][21][22][23][24] In recent decades, the diagnostic procedure most frequently employed to detect the 22q11.2 deletion has been fluorescent in situ hybridization (FISH) using commercial probes for regions between LCR22-A and LCR22-B (ie, in the proximal part of the TDR). In the past 10 years, a number of molecular biology techniques have been developed.…”

Section: Introductionmentioning

confidence: 99%

A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

Poirsier¹,

Besseau-Ayasse²,

Schluth-Bolard³

et al. 2015

Eur J Hum Genet

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Although 22q11.2 deletion syndrome (22q11.2DS) is the most recurrent human microdeletion syndrome associated with a highly variable phenotype, little is known about the condition's true incidence and the phenotype at diagnosis. We performed a multicenter, retrospective analysis of postnatally diagnosed patients recruited by members of the Association des Cytogénéticiens de Langue Française (the French-Speaking Cytogeneticists Association). Clinical and cytogenetic data on 749 cases diagnosed between 1995 and 2013 were collected by 31 French cytogenetics laboratories. The most frequent reasons for referral of postnatally diagnosed cases were a congenital heart defect (CHD, 48.6%), facial dysmorphism (49.7%) and developmental delay (40.7%). Since 2007 (the year in which array comparative genomic hybridization (aCGH) was introduced for the routine screening of patients with intellectual disability), almost all cases have been diagnosed using FISH (96.1%). Only 15 cases (all with an atypical phenotype) were diagnosed with aCGH; the deletion size ranged from 745 to 2904 kb. The deletion was inherited in 15.0% of cases and was of maternal origin in 85.5% of the latter. This is the largest yet documented cohort of patients with 22q11.2DS (the most commonly diagnosed microdeletion) from the same population. French cytogenetics laboratories diagnosed at least 108 affected patients (including fetuses) per year from among a national population of ∼ 66 million. As observed for prenatal diagnoses, CHDs were the most frequently detected malformation in postnatal diagnoses. The most common CHD in postnatal diagnoses was an isolated septal defect.

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Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia

Cited by 212 publications

References 29 publications

RBM15-MKL1 (OTT-MAL) fusion transcript in an adult acute myeloid leukemia patient

RBM15-MKL1 (OTT-MAL) fusion transcript in an adult acute myeloid leukemia patient

The Notch signaling pathway: Transcriptional regulation at Notch target genes

A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

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