Cloning the breakpoint cluster region of the inv(16) in acute nonlymphocytic leukemia M4 Eo

Dauwerse, J.G.; Wessels, J.; Giles, Rachel; Wiegant, J.; Reijden, Bert A. van der; Fugazza, Giuseppina; Jumelet, E. A.; Smit, E. M. E.; Baas, Frank; Raap, A.K.; Hagemeijer, Anne; Baverstock, G.C.; Ommen, G.J.B. van; Breuning, MH

doi:10.1093/hmg/2.10.1527

Cited by 41 publications

(25 citation statements)

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“…[85][86][87][101][102][103][104][105][106][107] The demonstration of unexpected large deletions in CML has prompted a number of FISH studies of other chromosomal translocations 51,108,109 (Table 4). Deletions have been described in association with a number of these translocations, with an incidence of between 2% and 16%.…”

Section: A Paradigm For Other Tumors Associated With Reciprocal Chrommentioning

confidence: 99%

Double jeopardy from a single translocation: deletions of the derivative chromosome 9 in chronic myeloid leukemia

Huntly¹,

Bench²,

Green³

2003

Blood

114

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Chronic myeloid leukemia (CML) is characterized by formation of a BCR-ABL fusion gene, usually as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22. Recently the development of new fluorescence insitu hybridization (FISH) techniques has allowed identification of unexpected deletions of the reciprocal translocation product, the derivative chromosome 9, in 10% to 15% of patients with CML. These deletions are large, span the translocation breakpoint, and occur at the same time as the Ph translocation. Such deletions therefore give rise to previously unsuspected molecular heterogeneity from the very beginning of this disease, and there is mounting evidence for similar deletions associated with other translocations. Several studies have demonstrated that CML patients who carry derivative chromosome 9 deletions exhibit a more rapid progression to blast crisis and a shorter survival. Deletion status is independent of, and more powerful than, the Sokal and Hasford/European prognostic scoring systems. The poor prognosis associated with deletions is seen in patients treated with hydroxyurea or interferon, and preliminary evidence suggests that patients with deletions may also have a worse outcome than nondeleted patients following stem cell transplantation or treatment with imatinib. Poor outcome cannot be attributed to loss of the reciprocal ABL-BCR fusion gene expression alone, and is likely to reflect loss of one or more critical genes within the deleted region. The molecular heterogeneity associated with the Philadelphia translocation provides a new paradigm with potential relevance to all malignancies associated with reciprocal chromosomal translocations and/or fusion gene formation. IntroductionChronic myeloid leukemia (CML) is a clonal hematologic malignancy that arises in the stem cell compartment. [1][2][3] Its molecular hallmark is the BCR-ABL fusion gene, 4,5 which usually occurs as the result of the Philadelphia (Ph) translocation involving the long arms of chromosomes 9 and 22. 6 The chimeric BCR-ABL gene encodes a constitutively activated protein tyrosine kinase, which leads to the activation of multiple signaling pathways, with profound effects on cell cycle, adhesion, and apoptosis. 2,3 In murine transgenic and retroviral transduction models, expression of BCR-ABL has been shown to be both sufficient for initiation and necessary for maintenance of a leukemic phenotype. [7][8][9][10][11][12][13][14] The natural history of CML follows a biphasic pattern with an initial chronic phase, which is often asymptomatic. This is inevitably followed by progression of the disease through an ill-defined stage termed accelerated phase to the terminal blast crisis. During chronic phase, the myeloid compartment is expanded but the cells retain their capacity to differentiate and function normally, and drug treatment is usually effective. By contrast, blast crisis is characterized by loss of differentiation capacity together with refractoriness to therapy and is associated with the acquisit...

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Section: A Paradigm For Other Tumors Associated With Reciprocal Chrommentioning

confidence: 99%

Double jeopardy from a single translocation: deletions of the derivative chromosome 9 in chronic myeloid leukemia

Huntly¹,

Bench²,

Green³

2003

Blood

114

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“…Cosmid RT53 was subcloned from YAC 262A3 of the Washington University YAC library, 39 using established methods. 40 Chromosome 8 cosmids were identified by screening a flow-sorted chromosome 8 cosmid library 41 with a 0.45 kb MOZ cDNA fragment (bp 4312-4764) and a 0.7 kb MOZ genomic fragment generously provided by J Borrow. 6 The 0.7 kb MOZ genomic fragment was sequenced using fluorescein isothiocyanate (FITC)-labeled deoxyadenosine triphosphate (dATP) and running on the Automated Laser Fluorescent DNA sequencing apparatus according to the manufacturer's instructions (Autoread kit, fluorescent dATP labeling mix, ALF, Pharmacia).…”

Section: Dna Extraction and Southern Blot Hybridizationmentioning

confidence: 99%

Detection of CBP rearrangements in acute myelogenous leukemia with t(8;16)

et al. 1997

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The CREB-binding protein (CBP) is a large nuclear protein that regulates many signal transduction pathways and is involved in chromatin-mediated transcription. The translocation t(8;16)(p11;p13.3) consistently disrupts two genes: the CBP gene on chromosome band 16p13.3 and the MOZ gene on chromosome band 8p11. Although a fusion of these two genes as a result of the translocation is expected, attempts at detecting the fusion transcript by reverse transcriptase polymerase chain reaction (RT-PCR) have proven difficult; to date, only one inframe CBP/MOZ fusion transcript has been reported. We therefore sought other reliable means of detecting CBP rearrangements. We applied fluorescence in situ hybridization (FISH) and Southern blot analyses to a series of AML patients with a t(8;16) and detected DNA rearrangements of both the CBP and the MOZ loci in all cases tested. All six cases examined for CBP rearrangements have breakpoints within a 13 kb breakpoint cluster region at the 5′ end of the CBP gene. Additionally, we used a MOZ cDNA probe to construct a surrounding cosmid contig and detect DNA rearrangements in three t(8;16) cases, all of which display rearrangements within a 6 kb genomic fragment of the MOZ gene. We have thus developed a series of cosmid probes that consistently detect the disruption of the CBP gene in t(8;16) patients. These clones could potentially be used to screen other cancer-associated or congenital translocations involving chromosome band 16p13.3 as well.

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“…Two cosmid contigs (each approximately of 100 kb), cloned by Dauwerse et al 8 and mapping to either side of the p-arm breakpoint region of chromosome 16 were used as probes. The proximal contig consisted of cosmids zit 14, zit 18, zit 38.…”

Section: Dual-color Fishmentioning

confidence: 99%

“…Moreover, CC cannot detect cryptic deletions of sequences centromeric to the p-arm breakpoint which have been described in a subset of inv(16) AML patients, accounting for 18-33% of cases. [7][8][9][10] The RT-PCR is able to detect CBF␤/MYH11 fusion transcript in the majority of inv(16)-positive cases at diagnosis; however, some cases remain RT-PCR negative. This finding might be caused by the diversity among inv(16) chimeric transcripts, together with the presence of alternatively spliced transcripts or poor quality RNA.…”

Section: Introductionmentioning

confidence: 99%

“…16 Although applicable on interphase cells, the YAC gives false negative results in cases of concomitant 16p deletion. 16 In the present study we analyzed 23 AML patients with CC clear or suspected inv (16), using a new set of cosmid contigs that allows interphase analysis, 8 with the aim of evaluating the efficacy of interphase dual-color FISH in detecting inv (16) at the onset of the disease, through its course and at relapse. Results were compared with CC and RT-PCR analysis of CBF␤/MYH11 transcript.…”

Section: Introductionmentioning

confidence: 99%

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Use of dual-color interphase FISH for the detection of inv(16) in acute myeloid leukemia at diagnosis, relapse and during follow-up: a study of 23 patients

et al. 2000

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Cloning the breakpoint cluster region of the inv(16) in acute nonlymphocytic leukemia M4 Eo

Cited by 41 publications

References 0 publications

Double jeopardy from a single translocation: deletions of the derivative chromosome 9 in chronic myeloid leukemia

Double jeopardy from a single translocation: deletions of the derivative chromosome 9 in chronic myeloid leukemia

Detection of CBP rearrangements in acute myelogenous leukemia with t(8;16)

Use of dual-color interphase FISH for the detection of inv(16) in acute myeloid leukemia at diagnosis, relapse and during follow-up: a study of 23 patients

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