Chronic Myeloid Leukemia: Current Application of Cytogenetics and Molecular Testing for Diagnosis and Treatment

Tefferi, Ayalew; Dewald, Gordon W.; Litzow, Mark; Cortes, Jorge; Mauro, Michael J.; Talpaz, Moshe; Kantarjian, Hagop M.

doi:10.4065/80.3.390

Cited by 57 publications

(45 citation statements)

References 164 publications

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“…Different from, for example, chronic myeloid leukemia where the formation of specific translocation chromosomes is accepted as being crucial for tumor development (Tefferi et al, 2005), the role of most chromosomal aberrations in solid tumors is still elusive. This is also the case for the aberrations identified for the different tumor-derived cell lines.…”

Section: Discussionmentioning

confidence: 99%

UVA radiation causes DNA strand breaks, chromosomal aberrations and tumorigenic transformation in HaCaT skin keratinocytes

et al. 2008

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The role of UVA-radiation-the major fraction in sunlight-in human skin carcinogenesis is still elusive. We here report that different UVA exposure regime (4 Â 5 J/cm 2 per week or 1 Â 20 J/cm 2 per week) caused tumorigenic conversion (tumors in nude mice) of the HaCaT skin keratinocytes. While tumorigenicity was not associated with general telomere shortening, we found new chromosomal changes characteristic for each recultivated tumor. Since this suggested a nontelomere-dependent relationship between UVA irradiation and chromosomal aberrations, we investigated for alternate mechanisms of UVA-dependent genomic instability. Using the alkaline and neutral comet assay as well as c-H2AX foci formation on irradiated HaCaT cells (20-60 J/cm 2 ), we show a dosedependent and long lasting induction of DNA single and double (ds) strand breaks. Extending this to normal human skin keratinocytes, we demonstrate a comparable damage response and, additionally, a significant induction and maintenance of micronuclei (MN) with more acentric fragments (indicative of ds breaks) than entire chromosomes particularly 5 days post irradiation. Thus, physiologically relevant UVA doses cause long-lasting DNA strand breaks, a prerequisite for chromosomal aberration that most likely contribute to tumorigenic conversion of the HaCaT cells. Since normal keratinocytes responded similarly, UVA may likewise contribute to the complex karyotype characteristic for human skin carcinomas.

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Section: Discussionmentioning

confidence: 99%

UVA radiation causes DNA strand breaks, chromosomal aberrations and tumorigenic transformation in HaCaT skin keratinocytes

et al. 2008

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“…2 There are many laboratory techniques available to detect and quantify minimal residual disease, including standard cytogenetics, fluorescence in situ hybridization, and polymerase chain reaction (PCR)-based detection of residual malignant cells. 3 Classic cytogenetics (chromosome G-banding) is still considered essential to establish a new diagnosis of CML. In addition to its high specificity in detecting the presence of the t(9;22) translocation, this technique provides the benefit of uncovering other chromosomal abnormalities, thus allowing for more reliable prognostication.…”

mentioning

confidence: 99%

Evaluation of the Cepheid GeneXpert BCR-ABL Assay

Jobbágy

Atta²,

Murphy

et al. 2007

The Journal of Molecular Diagnostics

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Patients with chronic myeloid leukemia harbor the chromosomal translocation t(9;22), which corresponds to fusion of the BCR and ABL genes at the DNA level. The translated fusion product is an oncogenic protein with increased ABL tyrosine kinase activity causing cell transformation. To date, reverse transcriptase-polymerase chain reaction is considered the most sensitive method available for detecting low copy numbers of the BCR-ABL gene fusion. Recently, Cepheid introduced its GeneXpert-based assay for the identification of the BCR-ABL gene fusion in cells from blood samples. This system comprises a walkaway self-contained instrument that combines cartridge-based microfluidic sample preparation with reverse transcriptase-polymerase chain reaction-based fluorescent signal detection and BCR-ABL and ABL Ct (threshold cycle) determination. The difference between the BCR-ABL Ct and ABL Ct (⌬Ct) is expected to represent the ratio of the two populations of mRNAs and ultimately the percentage of neoplastic cells present. We tested whether this BCR-ABL fusion detection system could be used as a clinical diagnostic tool for monitoring patients with minimal residual disease of chronic myelogenous leukemia. We report similar performance characteristics, including limit of detection, specificity, sensitivity, and precision, of this automated BCR-ABL fusion detection system to those of a manual TaqMan reverse transcriptase-polymerase chain reaction-based test.

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“…In CML, modern D-FISH strategies use a "green" probe to identify BCR and a "red" one to highlight ABL. A yellow signal indicates the presence of a BCR-ABL fusion sequence (Tefferi, 2005). This technique allows to detect not only the presence, but also the copy number of the fusion gene on the Ph, as well as the number of any additional BCR-ABL-bearing chromosomes, such as the ones resulting from variant translocations, cryptic translocations or insertions (Dewald, 1998).…”

Section: Fishmentioning

confidence: 99%

The Value of Molecular Response in Chronic Myeloid Leukemia: The Present and the Future

Falchi¹,

Appolloni²,

Ferranti³

et al. 2012

Myeloid Leukemia - Clinical Diagnosis and Treatment

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Chronic Myeloid Leukemia: Current Application of Cytogenetics and Molecular Testing for Diagnosis and Treatment

Cited by 57 publications

References 164 publications

UVA radiation causes DNA strand breaks, chromosomal aberrations and tumorigenic transformation in HaCaT skin keratinocytes

UVA radiation causes DNA strand breaks, chromosomal aberrations and tumorigenic transformation in HaCaT skin keratinocytes

Evaluation of the Cepheid GeneXpert BCR-ABL Assay

The Value of Molecular Response in Chronic Myeloid Leukemia: The Present and the Future

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