References of "Hagemeijer, A"
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See detailMolecular cytogenetic study of 126 unselected T-ALL cases reveals high incidence of TCR beta locus rearrangements and putative new T-cell oncogenes
Cauwelier, B.; Dastugue, N.; Cools, J. et al

in Leukemia (2006), 20(7), 1238-1244

Chromosomal aberrations of T-cell receptor (TCR) gene loci often involve the TCR alpha delta (14q11) locus and affect various known T-cell oncogenes. A systematic fluorescent in situ hybridization (FISH ... [more ▼]

Chromosomal aberrations of T-cell receptor (TCR) gene loci often involve the TCR alpha delta (14q11) locus and affect various known T-cell oncogenes. A systematic fluorescent in situ hybridization (FISH) screening for the detection of chromosomal aberrations involving the TCR loci, TCRad (14q11), TCR beta (7q34) and TCR gamma (7p14), has not been conducted so far. Therefore, we initiated a screening of 126 T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma cases and 19 T-ALL cell lines using FISH break-apart assays for the different TCR loci. Genomic rearrangements of the TCR beta locus were detected in 24/ 126 cases (19%), most of which (58.3%) were not detected upon banding analysis. Breakpoints in the TCR alpha delta locus were detected in 22/ 126 cases (17.4%), whereas standard cytogenetics only detected 14 of these 22 cases. Cryptic TCR alpha delta/ TCR beta chromosome aberrations were thus observed in 22 of 126 cases (17.4%). Some of these chromosome aberrations target new putative T-cell oncogenes at chromosome 11q24, 20p12 and 6q22. Five patients and one cell line carried chromosomal rearrangements affecting both TCR beta and TCR alpha delta loci. In conclusion, this study presents the first inventory of chromosomal rearrangements of TCR loci in T-ALL, revealing an unexpected high number of cryptic chromosomal rearrangements of the TCR beta locus and further broadening the spectrum of genes putatively implicated in T-cell oncogenesis. [less ▲]

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See detailExpression analyses identify MLL as a prominent target of 11q23 amplification and support an etiologic role for MLL gain of function in myeloid malignancies
Poppe, B.; Vandesompele, J.; Schoch, C. et al

in Blood (2004), 103(1), 229-235

MLL amplification was recently recognized as a recurrent aberration in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), associated with adverse prognosis and karyotype complexity. Here we ... [more ▼]

MLL amplification was recently recognized as a recurrent aberration in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), associated with adverse prognosis and karyotype complexity. Here we present detailed results of fluorescence in situ hybridization (FISH) and expression analyses of MLL and 5 selected 11q candidate oncogenes (CBL, DDX6, ETS1, FLI1, and PLZF) in 31 patient samples and one cell line with 11q23 gain. FISH analyses revealed that the 11q23 amplicon invariably encompassed MLL, DDX6, ETS1, and FLI1, whereas expression analyses identified MLL and DDX6 as the most differentially expressed genes among samples with and without 11q23 copy gain or amplification. In MLL-amplified samples, a significant transcriptional up-regulation of MEIS1, PROML1, ADAM10, NKG2D, and ITPA was noted. Further analyses, designed to elucidate a possible role of the 11q overexpressed genes (MLL, DDX6, FLI1, and ETS1) in unselected MDS and AML samples, revealed a significant upregulation of MLL in MDS. Our findings confirm the MLL gene as a prominent target of 11q23 amplification and provide further evidence for an etiologic role for MLL gain of function in myeloid malignancies. In addition, our results indicate that the transcriptional program associated with MLL rearrangements and MLL overexpression displays significant similarities. [less ▲]

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See detailt(5;14)/HOX11L2-positive T-cell acute lymphoblastic leukemia. A collaborative study of the Groupe Francais de Cytogenetique Hematologique (GFCH)
Berger, R.; Dastugue, N.; Busson, M. et al

in Leukemia (2003), 17(9), 1851-1857

To accurately estimate the incidence of HOX11L2 expression, and determine the associated cytogenetic features, in T-cell acute lymphoblastic leukemia (T-ALL), the Groupe Francais de Cytogenetique ... [more ▼]

To accurately estimate the incidence of HOX11L2 expression, and determine the associated cytogenetic features, in T-cell acute lymphoblastic leukemia (T-ALL), the Groupe Francais de Cytogenetique Hematologique (GFCH) carried out a retrospective study of both childhood and adult patients. In total, 364 patients were included ( 211 children less than or equal to15 years and 153 adults), and 67 ( 18.5%) [ 47 children ( 22.4%) and 20 adults (13.1%)] were shown to either harbor the t(5; 14) q35; q32) translocation or express the HOX11L2 gene or both. Most of the common hematological parameters did not show significant differences within positive and negative populations, whereas the incidence of CD1a+/CD10+ and cytoplasmic CD3+ patients was significantly higher in positive than in negative children. Out of the 63 positive patients investigated by conventional cytogenetics, 32 exhibited normal karyotype, whereas the others 31 showed clonal chromosome abnormalities, which did not include classical T-ALL specific translocations. Involvement of the RANBP17/HOX11L2 locus was ascertained by fluorescence in situ hybridization in six variant or alternative (three-way translocation or cytogenetic partner other than 14q32) translocations out of the 223 patients. Our results also show that HOX11L2 expression essentially occurs as a result of a 5q35 rearrangement, but is not associated with another identified T-ALL specific recurrent genetic abnormality, such as SIL-TAL fusion or HOX11 expression. [less ▲]

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See detailThe stem cell mobilizing capacity of patients with acute myeloid leukemia in complete remission correlates with relapse risk: results of the EORTC-GIMEMA AML-10 trial
Keating, S.; Suciu, S.; de Witte, T. et al

in Leukemia (2003), 17(1), 60-67

Variable numbers of CD34(+) cells can be harvested from the blood of AML patients in CR after G-CSF supported mobilization following consolidation chemotherapy. We hypothesized that a decreased ability to ... [more ▼]

Variable numbers of CD34(+) cells can be harvested from the blood of AML patients in CR after G-CSF supported mobilization following consolidation chemotherapy. We hypothesized that a decreased ability to mobilize stem cells reflects a chemotherapy-induced reduction in the number of normal and leukemic stem cells. We therefore analyzed whether the mobilizing capacity of these patients was of prognostic significance. 342 AML-patients in first CR received daily G-CSF from day 20 of the consolidation course and underwent 1-6 aphereses to obtain a minimum dose of 2 x 10(6) CD34(+) cells/kg. Afterwards they were randomized for autologous bone marrow (M) or blood SCT. As a surrogate marker for the mobilizing capacity, the highest yield of CD34(+) cells of a single apheresis was adopted. Patients could be categorized into four groups: no harvest (n = 76), low yield (<1 x 10(6) CD34(+)/kg; n = 50), intermediate yield (1-6.9 x 10(6) CD34(+) cells/kg; n = 128) and high yield ( :7 x 106 CD34+ cells/kg; n = 88). The median follow-up was 3.4 years; 163 relapses and 16 deaths in CR were reported. Autologous blood or BM SCT was performed in 36%, 64%, 81% and 88%, respectively, of the patients assigned to the no harvest, low, intermediate and high CD34(+) yield group. The 3-year disease-free survival rate was 46.7%, 65.0%, 50.4% and 26.9% (P= 0.0002) and the relapse incidence was 47.5%, 30.1%, 43.1% and 71.9% (P < 0.0001). Multivariate Cox's proportional hazards model showed that the CD34(+) yield was the most important independent prognostic variable (P = 0.005) after cytogenetics. Patients with the highest mobilizing capacity have a poor prognosis due to an increased relapse incidence. [less ▲]

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See detailHistologic localization of PLAG1 (pleomorphic adenoma gene 1) in pleomorphic adenoma of the salivary gland: cytogenetic evidence of common origin of phenotypically diverse cells.
Debiec-Rychter, M.; Van Valckenborgh, I.; Van den Broeck, C. et al

in Laboratory Investigation : Journal of Technical Methods & Pathology (2001), 81(9), 1289-97

Pleomorphic adenoma gene 1 (PLAG1), a zinc finger transcription factor gene, is consistently rearranged and overexpressed in human pleomorphic adenomas of the salivary glands with 8q12 translocations. In ... [more ▼]

Pleomorphic adenoma gene 1 (PLAG1), a zinc finger transcription factor gene, is consistently rearranged and overexpressed in human pleomorphic adenomas of the salivary glands with 8q12 translocations. In this report, we describe the immunohistochemical localization of PLAG1 protein in pleomorphic adenomas of the salivary gland and corresponding normal tissue, in relation to cytokeratin, vimentin, and BCL-2 expression. Normal salivary gland tissue was not immunoreactive for PLAG1. In primary pleomorphic adenomas, cells strongly immunoreactive for PLAG1 were detected in the outer layer of tubulo-ductal structures, which are thought to be the origin of cells with bi-directional, epithelial, and mesenchymal phenotypes. In contrast, epithelial cells with abundant cytokeratin in the inner tubulo-ductal structures only sporadically expressed PLAG1. BCL-2 immunoreactivity was found mainly in the cells surrounding the tubulo-ductal structures and in the solid undifferentiated cellular masses, within the areas that had moderate PLAG1 immunoreactivity. The variability of PLAG1 expression in neoplastic cells seemed to reflect the morphologic heterogeneity that correlated with the stage of differentiation of the tumor cells. Immunohistochemical/cytogenetic evaluation of two pleomorphic adenomas with t(3;8)(p21;q12) or t(5;8)(p13;q12) translocations demonstrated the clonal nature of immunophenotypically diverse cells. This finding confirms the theory that pleomorphic adenoma cells share a common single-cell origin, most likely from the epithelial progenitor basal duct cells. [less ▲]

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