تأثير الطفرات في الـ IDH على مثيلة الدنا للجينات المرتبطة بسرطان الدم النخاعي الحاد: مقالة مراجعة

المؤلفون

DOI:

https://doi.org/10.32007/jfacmedbagdad.6612175

الكلمات المفتاحية:

AML; ، DNA methylation; ، DNA methyltransferases; ، IDH;، isocitrate dehydrogenase; ، targeted therapy; ، TET proteins;

الملخص

 

الخلفية العلمية: ابيضاض الدم النخاعي الحاد (AML) هو أحد أكثر الأورام الدموية الخبيثة فتكًا و تتميز بوظائف خلوية غير طبيعية وتغيرات جينية. و تبين ان الطفرات في جينات نازعة هيدروجين إيزوسيترات (IDH) وخاصة IDH1 و IDH2 ، على أنها تشوهات وراثية متكررة في مرضى ابيضاض الدم النخاعي الحاد .و تؤدي هذه الطفرات إلى نشاط إنزيمي غير طبيعي، مما يؤدي إلى تراكم 2-هيدروكسي جلوتارات  (2-HG)،,والذي بدوره يعطل العمليات الخلوية الطبيعية بما في ذلك مثيلة الحمض النووي.

الهدف: تهدف مقالة المراجعة هذه إلى استعراض الطفرات الجينية المسجلة لـ, IDH   التحقق من العلاقة بين تلك الطفرات والتغييرات في أنماط مثيلة الحمض النووي، وآثارها على التسبب في الإصابة بابيضاض الدم النخاعي الحاد والتنبؤ به وعلاجه.

المواد وطرق العمل: تم إجراء بحث شامل في الأدبيات العلمية لتحديد الدراسات ذات الصلة التي تبحث في تأثير طفرات IDH على الجينات المرتبطة بمثيل الحمض النووي في المرضى الذين يعانون من ابيضاض الدم.  وتمت مراجعة الدراسات المختارة وتحليلها لغرض الوصول الى المعلومات والمعرفة الحالية حول هذا الموضوع.

النتائج: سلطت هذه المقالة الضوء على أن طفرات IDH في AML مرتبطة بتغيرات واسعة النطاق في أنماط مثيلة الحمض النووي. تؤثر هذه التغييرات في المقام الأول على الجينات المرتبطة بإضافة مجموعة المثيل الى الحمض النووي، بما في ذلك DNA methyltransferases (DNMTs)  وبروتيناتTET.  بالتالي يؤدي خلل تنظيم مثيلة الحمض النووي إلى فرط مثيل الحمض النووي بصورة عامة بالإضافة الى جينات محددة بصورة خاصة، ووكون علامة المثيل الطبيعية تسهم في تنظيم التعبير الجيني، فأن هذا الاضطراب الجزيئي يساهم في اختلال الوظائف الخلوية الطبيعية ونشوء مرض AML.

الخلاصة: تدعم نتائج مقالة المراجعة هذه التأثير المهم لطفرات جين IDH على الجينات المرتبطة بمثيلة الحمض النووي في AML. و يوفر فهم التفاعل بين طفرات IDH وخلل تنظيم مثيلة الحمض النووي نظرة استكشافية لمسببات AML  والتنبؤ بتطوره ومجالا واعدا لتطوير العلاجات الاستهدافية ز.

 

الكلمات المفتاحية: AML ، نازعة هيدروجين الأيزوسيترات ، IDH ، مثيلة الحمض النووي DNA methylation ، DNA methyltransferases ، بروتينات TET ، العلاج الموجه.

 

الملخص الصوري

التنزيلات

تنزيل البيانات ليس متاحًا بعد.

السير الشخصية للمؤلفين

  • Duha M. Bayram، Department of Pharmacology and Toxicology, College of Pharmacy, Mustansiriyah University, Baghdad- Iraq

    Department of Pharmacology and Toxicology, College of Pharmacy, Mustansiriyah University, Baghdad- Iraq

  • Fadhel M. Lafta، Department of Biology, College of Science, Baghdad University, Baghdad-Iraq

    Department of Biology, College of Science, Baghdad University, Baghdad-Iraq

  • Bassam F. Matti، Haematology Centre, Medical City, Baghdad- Iraq

    Haematology Centre, Medical City, Baghdad- Iraq

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AML; , DNA methylation; , DNA methyltransferases; , IDH;, isocitrate dehydrogenase; , targeted therapy; , TET proteins;

التنزيلات

الملفات الإضافية

منشور

2024-04-01

كيفية الاقتباس

1.
M. Bayram D, M. Lafta F, F. Matti B. تأثير الطفرات في الـ IDH على مثيلة الدنا للجينات المرتبطة بسرطان الدم النخاعي الحاد: مقالة مراجعة. J Fac Med Baghdad [انترنت]. 1 أبريل، 2024 [وثق 24 نوفمبر، 2024];66(1):116-25. موجود في: https://iqjmc.uobaghdad.edu.iq/index.php/19JFacMedBaghdad36/article/view/2175

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