A DNA probe combination for improved detection of MLL/11q23 breakpoints by double-color interphase-FISH in acute leukemias

Bergh, A von; Emanuel, B.S.; Zelderen-Bhola, Shama van; Smetsers, T. F. C. M.; Soest, Ronald van; Stul, Michel; Vranckx, Hilde; Schuuring, Ed; Hagemeijer, Anne; Kluin, Philip M.

doi:10.1002/(sici)1098-2264(200005)28:1<14::aid-gcc2>3.3.co;2-o

Cited by 32 publications

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“…[84][85][86] FISH screening for MLL rearrangements at diagnosis has become the standard approach in many AML protocols. However, GEP has illustrated that current diagnostic techniques do not guarantee 100% sensitivity for detection of MLL rearrangements.…”

Section: The Detection Of Mll Rearrangementsmentioning

confidence: 99%

The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia

et al. 2011

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Translocations involving the mixed-lineage leukemia (MLL) gene, localized at 11q23, comprise 15 to 20% of all pediatric acute myeloid leukemia (AML) cases. This review summarizes current knowledge about the etiology, biology, clinical characteristics and differences in outcome in MLL-rearranged pediatric AML. Furthermore, we discuss the role of cooperating events in MLL-rearranged pediatric AML, and future therapeutic strategies to improve outcome. We conclude that MLL-rearranged pediatric AML is a heterogeneous disease, and prognosis depends on various factors, for example, translocation partner, age, WBC and additional cytogenetic aberrations. The relationship of outcome with specific translocation partners requires that they be searched for in the diagnostic work-up of AML. To achieve further improvements in outcome, unraveling the biology of MLL-rearranged pediatric AML is warranted.

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Section: The Detection Of Mll Rearrangementsmentioning

confidence: 99%

The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia

et al. 2011

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“…Bacterial artificial chromosome/phage artificial chromosome (BAC/PAC) clones were obtained from the Resources for Molecular Cytogenetics (RMC) database (http:// www.biologia.uniba.it/rmc/) in Italy: CTD-217A21 for the MLL gene (22) and RP11-476C8 for the AF4 gene. RP11-2344B19 for the ENL gene was purchased from Invitrogen (Carlsbad, CA, USA).…”

Section: Dna Probesmentioning

confidence: 99%

Smart 3D‐fish: Automation of distance analysis in nuclei of interphase cells by image processing

et al. 2005

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Background: Detection of fluorescent probes by fluorescence in situ hybridization in cells with preserved threedimensional nuclear structures (3D-FISH) is useful for studying the organization of chromatin and localization of genes in interphase nuclei. Fast and reliable measurements of the relative positioning of fluorescent spots specific to subchromosomal regions and genes would improve understanding of cell structure and function. Methods: 3D-FISH protocol, confocal microscopy, and digital image analysis were used. Results: New software (Smart 3D-FISH) has been developed to automate the process of spot segmentation and distance measurements in images from 3D-FISH experiments. It can handle any number of fluorescent spots and incorporate images of 4 0 ,6-diamino-2-phenylindole counterstained nuclei to measure the relative positioning of

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“…A FISH probe set was designed in such a way that the two probes flank both sides of the MLL breakpoint region without overlap (adapted from the probes described by van der Burg et al). 35,84 …”

Section: Translocations Involving the Mll Gene (11q23)mentioning

confidence: 99%

Split-signal FISH for detection of chromosome aberrations in acute lymphoblastic leukemia

Burg

Poulsen²,

Hunger

et al. 2004

Leukemia

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Chromosome aberrations are frequently observed in precursor-B-acute lymphoblastic leukemias (ALL) and T-cell acute lymphoblastic leukemias (T-ALL). These translocations can form leukemia-specific chimeric fusion proteins or they can deregulate expression of an (onco)gene, resulting in aberrant expression or overexpression. Detection of chromosome aberrations is an important tool for risk classification. We developed rapid and sensitive split-signal fluorescent in situ hybridization (FISH) assays for six of the most frequent chromosome aberrations in precursor-B-ALL and T-ALL. The split-signal FISH approach uses two differentially labeled probes, located in one gene at opposite sites of the breakpoint region. Probe sets were developed for the genes TCF3 (E2A) at 19p13, MLL at 11q23, ETV6 at 12p13, BCR at 22q11, SIL-TAL1 at 1q32 and TLX3 (HOX11L2) at 5q35. In normal karyotypes, two colocalized green/red signals are visible, but a translocation results in a split of one of the colocalized signals. Split-signal FISH has three main advantages over the classical fusionsignal FISH approach, which uses two labeled probes located in two genes. First, the detection of a chromosome aberration is independent of the involved partner gene. Second, split-signal FISH allows the identification of the partner gene or chromosome region if metaphase spreads are present, and finally it reduces false-positivity. Leukemia ( Chromosome aberrations play an important role in hematological malignancies. 1 In ALL, most of these aberrations concern balanced translocations involving genes that play key roles in the development and function of lymphoid cells, such as transcription factors, cell cycle regulators, and signal transduction molecules. Balanced translocations can result in fusion of two genes that encode leukemia-specific chimeric (fusion) proteins. The fusion proteins have functional features that differ from the corresponding wild-type proteins and mostly play a role in leukemogenesis. In addition to the new features of the fusion protein, loss of wild-type activity due to the translocation (in some translocations enhanced by deletion of the second allele) might contribute to oncogenesis. Alternatively, chromosome translocations can result in deregulated expression of (onco)genes as a direct consequence of a translocation to a regulatory element, for example, an immunoglobulin (Ig) or T-cell receptor (TCR) enhancer. 2,3 The most frequent translocations in precursor-B-ALL are t(1;19)(q23;p13) t(4;11)(q21;q23), t(12;21)(p13;q22), and t(9;22)(q34;q11), all four of which result in generation of fusion genes. The t(1;19)(q23;p13) fuses the transcription factorencoding gene TCF3 (E2A) with the transcription factor PBX1. In t(4;11)(q21;q23), the MLL gene at 11q23, which encodes a putative DNA-binding protein, is translocated to the MLLT2 (AF4) gene. The MLL gene is involved in many other translocations in ALL and acute myeloid leukemia (AML). Until now, more than 30 partner genes have been identified. 4 The t(12;21)(p13;q22) involves th...

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A DNA probe combination for improved detection of MLL/11q23 breakpoints by double-color interphase-FISH in acute leukemias

Cited by 32 publications

References 0 publications

The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia

The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia

Smart 3D‐fish: Automation of distance analysis in nuclei of interphase cells by image processing

Split-signal FISH for detection of chromosome aberrations in acute lymphoblastic leukemia

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