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Detection of bcr-abl1 mrna in platelets and cfrna from chronic myeloid leukaemia patients

Başlık çevirisi mevcut değil.

  1. Tez No: 797800
  2. Yazar: SERRA ÖZARI
  3. Danışmanlar: DR. JAMSHID SOROURI KHORASHAD, DR. KATHY DOMINY
  4. Tez Türü: Yüksek Lisans
  5. Konular: Genetik, Moleküler Tıp, Genetics, Molecular Medicine
  6. Anahtar Kelimeler: Belirtilmemiş.
  7. Yıl: 2019
  8. Dil: İngilizce
  9. Üniversite: Imperial College London
  10. Enstitü: Yurtdışı Enstitü
  11. Ana Bilim Dalı: Belirtilmemiş.
  12. Bilim Dalı: Belirtilmemiş.
  13. Sayfa Sayısı: 59

Özet

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Özet (Çeviri)

Chronic Myeloid Leukaemia (CML) is a bone marrow cancer of white blood cells originating from myeloid stem cell lineage, causing uncontrolled proliferation and accumulation of granulocytes. It is characterized by formation of BCR-ABL1 fusion oncogene, also referred to as Philadelphia chromosome, through reciprocal translocation between chromosomes 9 and 22, which results in constitutively active BCR-ABL1 tyrosine kinase and consequently abnormal alterations in the activation of the downstream effectors/signalling pathways. Regular monitoring of residual BCRABL1 transcript levels in CML patients provides crucial information about molecular response of patients to an applied treatment, as well as their prognosis and predicted clinical outcome. Patients achieving more than 4 log reductions in their BCR-ABL1 transcript numbers (equal or less than 0.01 % BCR-ABL1 of the original amount) are considered to be expressing a“deep molecular response”which is an essential indicator for the patient to enter treatment-free disease remission phase. Existing quantitative (real-time) polymerase chain reaction (qPCR) detection is not sensitive enough to differentiate patients who lose their deep molecular response upon stopping therapy from those who still acquire it. This paper aimed to investigate an alternative and novel detection method of BCR-ABL1 transcripts in platelets and blood plasma (as in cell-free RNA form) rather than in white blood cells, with qPCR as a potential prognostic measure to further investigate minimal residual disease especially in patients with undetectable transcript levels in their white blood cells (WBCs). In this study, our hypothesis was that BCR-ABL1 transcripts could be detected in cfRNA and especially in platelets with higher sensitivity compared to WBCs. Results showed that, detection of BCR-ABL1 mRNA in white blood cells was still much more sensitive compared to attempting to determine the levels in platelets and cfRNA. Platelets and cfRNA weren't found to be better sources than white blood cells for monitoring of transcript levels, at least not in CML

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