Annotated bibliography - Part 5

Annotated bibliography

Park TS, Lee ST, Kim JS, Song J, LeE KA,Kim SJ, Seok YM, Lee HJ, Han JH, Kim JK, Lee EY, Choi JR.  Acute promyelocytic leukemia in early pregnancy with translocation t(15;17) and variant PML/RARA fusion transcripts.  Cancer Genetics and Cytogenetics.  2008; 188:48-51.

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            The research article of Park et al. presents a case report that involves a pregnant woman who was determined to have a chromosomal rearrangement characteristic of acute promyelocytic leukemia.  This report provides a unique view on the incidence of this specific type of acute leukemia during pregnancy, which has been considered as a rare event, affecting only one in almost 100,000 pregnancies.  The employment of both karyotypic and molecular biology tools has elucidated the actual condition of the patient, including the identification of variant transcripts that were generated from the translocation of genetic material between chromosomes 15 and 17.

            Acute leukemia pertains to a blood disorder that generally afflicts adults and is characterized by the generation of a high number of leucocytes.  The treatment of acute leukemia becomes complicated when it involves pregnant women, as there is an immediate need to administer anti-cancer medications in order to prevent the further proliferation of leucocytes.  The termination of the developing fetus is thus a common action that is performed upon positive diagnosis of acute leukemia in a pregnant woman.

            The incidence of leukemia in pregnant women has been estimated to be one in at most 100,000 pregnancies each year.  Moreover, acute leukemia cases only comprise 350 of these reported incidents, of which only 50 have been designated as acute promyelocytic leukemia.  With such low incidence among pregnant women each year, this specific condition has thus been recognized as a rare condition.

            The case study of Park et al. describes the presentation of a 32-year old pregnant woman with a chief complaint of hemorrhage in the gums, as well as rapid bruising.  A number of tests, including complete blood and platelet counts, as well as hemoglobin and fibrinogen levels were performed in order to determine the blood constituency of the patient.  In addition, a blood and a bone marrow smear were conducted to determine the patient’s leucocyte count.  Karyotypic analysis showed that the patient has a mosaic constitution of normal 46,XX and 46,XX,t(15;17).

            One important procedure that was performed in this study is the reverse transcriptase-polymerase chain reaction, which allowed the investigators to determine the actual rearrangement of genes involved in the etiology of acute promyelocytic leukemia.  Using three breakpoint cluster regions that spanned the gene loci of PML and RARA, copies of the DNA segments between the designed forward and reverse primers generated two variants of the second breakpoint cluster region (brc2).  Two bands were also visualized in the agarose gel, with molecular weights of 714 and 574 bp, respectively.  The larger band represented a bcr2 variant that had lost exon 5, while the smaller band represented another bcr2 variant with a deleted exon 6.  The bcr1 and bcr3 variants were not detected in the DNA sample isolated from the patient.

            This article presents the relevance of detecting fusion transcripts using molecular biology techniques in order to precisely determine the type of acute promyelocytic leukemia that each patient has developed.  In addition, the identification of breakpoints in acute promyelocytic leukemia will also provide information of the frequency of each variant in the general population.  The investigators have emphasized the importance of performing differential diagnosis in order to design a personalized therapeutic regimen for every patient.  The combination of clinical, molecular and differential information is therefore the most effective approach in treating patients with acute promyelocytic leukemia.

Reference

Park TS, Lee ST, Kim JS, Song J, LeE KA,Kim SJ, Seok YM, Lee HJ, Han JH, Kim JK, Lee EY, Choi JR.  Acute promyelocytic leukemia in early pregnancy with translocation t(15;17) and variant PML/RARA fusion transcripts.  Cancer Genetics and Cytogenetics.  2008; 188:48-51.

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