اختلال در مسیر پیام‌رسانی Wnt از طریق متیلاسیون ژن‌های 1WIF و 1DKK در بیماران مبتلا به لوسمی میلوییدی حاد در زمان تشخیص بیماری

نوع مقاله : مقاله های پژوهشی

نویسندگان

1 کارشناس ارشد، گروه هماتولوژی، دانشکده‌ی پیراپزشکی، دانشگاه علوم پزشکی تهران، تهران، ایران

2 گروه بیوتکنولوژی، دانشکده‌ی پیراپزشکی، دانشگاه علوم پزشکی تهران، تهران، ایران

3 مربی، گروه هماتولوژی، دانشکده‌ی پیراپزشکی، دانشگاه علوم پزشکی اراک، اراک، ایران

چکیده

مقدمه: لوسمی میلوییدی حاد (AML یا Acute myeloid leukemia) گروه هتروژنی از بدخیمی‌های هماتولوژیک می‌باشند که عوامل زیادی در پاتوژنز آن‌ها دخیل هستند. در AML، تعداد زیادی از ژن‌های سرکوب کننده‌ی تومور مثل B2CDKN و 73p طی فرایند DNA متیلاسیون خاموش می‌شوند. پروتئین‌های 1WIF (1Wnt inhibitory factor) و 1DKK (1Dickkopf)، تنظیم کننده‌های منفی مسیر پیام‌رسانی Wntمی‌باشند. در مطالعه‌ی حاضر، وضعیت متیلاسیون ژن‌های 1WIF و 1DKK در بیماران مبتلا به AML مورد بررسی قرار گرفت.روش‌ها: نمونه‌ی خون 120 بیمار مبتلا به AML و 30 فرد سالم به عنوان شاهد گرفته شد. DNA نمونه‌ها استخراج و با سدیم بی‌سولفید تیمار دارویی گردید. برای بررسی وضعیت متیلاسیون ژن‌ها، از تکنیک MSP (Methylation specific-polymerase chain reaction) با پرایمرهای اختصاصی برای توالی متیله و غیر متیله‌ی ژن‌های 1WIF و 1DKK استفاده شد.یافته‌ها: درصد هایپرمتیلاسیون برای ژن‌های 1WIF و 1DKK به ترتیب 0/35 (120/42) و 3/28 درصد (120/34) بود. در هیچ کدام از نمونه‌های شاهد که مربوط به افراد سالم بودند، متیلاسیون این دو ژن مشاهده نشد. بیشترین هایپرمتیلاسیون ژن 1WIF (0030/0 = P) و ژن 1DKK (0050/0 = P) در بیماران با زیر گروه 0AML-M مشاهده شد.نتیجه‌گیری: در مطالعه‌ی حاضر مشاهده شد که همانند بسیاری از تومورهای توپر، متیلاسیون ژن‌های 1WIF و 1DKK در AML نیز اتفاق می‌افتد. از این رو احتمال می‌رود که متیلاسیون این ژن‌ها در شروع بیماری نقش داشته باشد. 

کلیدواژه‌ها

عنوان مقاله [English]

Dysregulation of the Wnt Signaling Pathway through Methylation of WIF1and DKK1 Genes in Patients with Acute Myeloid Leukemia (AML) at the Time of Diagnosis

نویسندگان [English]

  • Ali Ghasemi 1
  • Mohsen Mohammadi 2
  • Abbas Ghotaslou 1
  • Kazem Ghaffari 3
  • Sadegh Abbasian 1
1 Department of Hematology, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Biotechnology, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
3 Instructor, Department of Hematology, School of Allied Medical Sciences, Arak University of Medical Sciences, Arak, Iran
چکیده [English]

Background: In acute myeloid leukemia (AML), a large number of tumor suppressor genes are silenced through DNA methylation such as CDKN2B and p73. Wnt inhibitory factor 1 (WIF1) and Dickkopf-1 (DKK-1) are negative regulator of the Wnt signaling pathway. In the present study, we studied the methylation status of WIF1 and DKK-1 genes in patients with acute myeloid leukemia.Methods: Blood samples from 120 patients with acute myeloid leukemia and 25 healthy control subjects were taken. Isolated DNA was treated with sodium bisulphite and examined via methylation-specific polymerase chain reaction (MSP) with primers specific for methylated and unmethylated sequences of the WIF1 and DKK-1 genes.Findings: The frequency of aberrant hypermethylation of WIF1 and DKK-1 genes in patients with acute myeloid leukemia was determined 35.0% (42/120) and 28.3% (34/120), respectively. In addition, for all subjects in control group, methylation of WIF1 and DKK-1 genes were negative. Patients with M0 subtype of French-American-British acute myeloid leukemia (FAB-AML) had the highest incidence of hypermethylation of WIF1 (P = 0.003) and DKK-1 (P = 0.005) genes.Conclusion: The present study showed that, like many solid tumors, WIF1 and DKK-1 genes methylation also occurs in acute myeloid leukemia. Therefore, the methylation of these genes may play a role in leukmogenesis initiation.

کلیدواژه‌ها [English]

  • DNA Methylation
  • WIF1
  • DKK
  • Acute myeloid leukemia

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مجله دانشکده پزشکی اصفهان
دوره 32، شماره 306 - شماره پیاپی 306
آذر و دی 1393
صفحه 1757-1766

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  • تاریخ دریافت: 21 مرداد 1393
  • تاریخ بازنگری: 11 آبان 1403
  • تاریخ پذیرش: 17 فروردین 1401

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