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Complex translocation

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Miyazaki K, Kikukawa M, Kiuchi A, Shin K, Iwamoto T, Ohyashiki K.  Complex translocations derived stepwise from standard t(15;17) in a patient with variant acute promyelocytic leukemia.

Cancer Genetics and Cytogenetics. 2007; 176:127-130.

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            The article of Miyazaki et al. is a case report that involved an elderly male patient who was diagnosed with acute promyelocytic leukemia with unique chromosomal rearrangements.  Aside from the hallmark translocation between chromosomes 15 and 17, the patient also carried additional chromosomes that were related to the aberration.  The report also provides another perspective in employing classical karyotyping, fluorescence in situ hybridization and spectral karyotyping techniques in the elucidation of the actual clonal origin of the translocation that resulted in acute promyelocytic leukemia.

            The patient described in this case report was presented to the investigators with a chief complaint of general fatigue.  In addition, the patient expressed that he was suffering from a cold for the last 30 days.  Blood work was performed on the patient, including that of complete blood and platelet counts, as well as determination of fibrinogen levels.

  The bone marrow smear showed that almost 65% of the cells were comprised of promyelocytes that were characterized with microgranules in the cytoplasmic area.  Upon administration of ATRA, the patient underwent complete remission for approximately 14 months.

            In an attempt for fully understand the clonal origin and generation of acute promyelocytic leukemia in this particular case, a number of cytogenetic assays were performed.  Classical karyotyping using trypsin and Giemsa staining showed that the patient carried a translocation between chromosomes 15 and 17.  However, two derivative chromosomes were also identified, each of which originated from the major chromosomes involved in the translocation.  Another interesting finding was that an additional chromosome was also linked to the gross rearrangement.  The derivative of chromosome 17 was thus observed to interact with the long arm of chromosome 8.

            Fluorescence in situ hybridization also showed the relative locations of two genes involved in the etiology of acute promyelocytic leukemia.  The PML gene is located along the long arm of chromosome 15, while that RARA gene is positioned on the long arm of chromosome 17.  The translocation that is commonly observed in acute promyelocytic leukemia cases can thus be verified using the dual-color translocation probe for PML-RARA, wherein the close proximity of these two genes would directly indicate a translocation.  On the other hand, the separation of these genes in a cell would represent a normal chromosomal setting.  The results of this assay showed that 91% of the cells analyzed carried the fused genes of PML and RARA.

            Spectral karyotyping of the patient chromosomes assisted in the analysis of the finer details of the chromosomal rearrangements that have taken place within the cells.  Using five fluorophores that were combinatorially introduced to each chromosome, it is thus possible to assign a particular color to every chromosome pair.  The results of the spectral karyotyping assay showed that there were three types of clones that were related to the development of acute promyelocytic leukemia.  One clonal type involved the simple translocation of genetic material between chromosomes 15 and 17.  The second clonal type involved that transfer of chromosomal segments from chromosomes 8 and 15 and its reintroduction into chromosome 17.  The third clonal type involved the transfer of genetic material from chromosomes 8, 15 and 17 and its subsequent reintroduction into chromosome 14.  In addition, there were also chromosome segments originating from chromosomes 8 and 15 that were inserted into the acceptor chromosome 17.

            This case study provides a unique perspective into the molecular genetic etiology of acute promyelocytic leukemia.  The elucidation of the stepwise transfer of genetic material from the donor chromosomes, such as chromosomes 8, 15 and 17, provides additional information on the progression of the disease.  The information provided from this case study may also be employed in the design of future research studies on the genetic aspects of acute promyelocytic leukemia.  It is thus highly likely that there would be more chromosomal rearrangements that would be documented in the future and these may be similar to what has been described in this case study.

Reference

Miyazaki K, Kikukawa M, Kiuchi A, Shin K, Iwamoto T, Ohyashiki K.  Complex translocations derived stepwise from standard t(15;17) in a patient with variant acute promyelocytic leukemia. Cancer Genetics and Cytogenetics. 2007; 176:127-130.

 

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Complex translocation. (2016, Sep 02). Retrieved from https://graduateway.com/complex-translocation/

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