fa ارتباط پیش آگهی نوع ترانسکریپت BCR-ABL1٬ Sokal Score و سیگار به عنوان عامل سینرژیسم با پاسخ کامل سیتوژنتیکی در بیماران لوسمی میلوئیدی مزمن تحت درمان با روش‌های مختلف مهار کنندگان تیروزین کینازی انكولوژي Oncology كوهورت Cohort <span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><span style="font-weight:bold"><span lang="FA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:">سابقه و هدف</span></span><i><span lang="FA" style="font-size:12.0pt"><span style="font-family:Nazanin"><span style="font-weight:normal">:</span></span></span></i> <i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="font-weight:normal">در بیماری </span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="font-weight:normal">CML</span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="font-weight:normal"> تاثیر نوع ترانسکریپت، </span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="font-weight:normal">Sokal score</span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="font-weight:normal"> ودود سیگار روی فنوتیپ بیماری و پاسخ سیتوژنتیکی به درمان هنوز ناشناخته و بحث برانگیز است. هدف از این مطالعه تعیین اهمیت پیش آگهی نوع ترانسکریپت</span></span></span></i><span b="" nazanin="" style="font-family:"><span style="font-weight:normal">، </span></span><i><span dir="LTR" style="font-size:10.0pt"><span style="font-weight:normal">Sokal score</span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="font-weight:normal"> و سیگار در بیماران </span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="font-weight:normal">CML</span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="font-weight:normal"> تحت درمان با روش&shy;های مختلف درمانی تیروزین کینازی بود</span></span></span></i><i><span lang="FA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="font-weight:normal">. </span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="font-weight:normal"></span></span></i></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><span style="font-weight:bold"><span lang="FA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.3pt">روش بررسی</span></span></span><i><span lang="FA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.3pt"><span style="font-weight:normal">:</span></span></span></span></i> <i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">در این مطالعه 60 بیمار مبتلا به </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">CML</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> در آنالیز وارد شدند. تایپینگ مولکولی جهت تعیین نوع ترانسکریپت به وسیله </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">Multiplex RT-PCR</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> انجام شد و پروتکل استاندارد بندینگ جهت پیگیری پاسخ سیتوژنتیکی در فواصل 3 و 6 ماه به کار برده شد.&nbsp; </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal"></span></span></span></i></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><span style="font-weight:bold"><span lang="FA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt">یافته</span></span></span><span lang="FA" style="font-size:14.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">&shy;</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt">ها:</span></span></span> <i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">عمومی&shy;ترین نوع ترانسکریپت</span></span></span></span></i><span b="" nazanin="" style="font-family:"><span style="font-weight:normal">، </span></span><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">e14a2</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> (3/58 درصد) بود. در بروز تجمعی پاسخ کامل سیتوژنتیکی بین دو گروه ترانسکریپت </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">e14a2</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> و</span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">e13a2</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> تفاوت معنی داری وجود داشت (</span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">P=0.04</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">). زمان دریافت پاسخ کامل سیتوژنتیکی در بیماران دارای ترانسکریپت </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">e14a2</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> کوتاه&shy;تر بود (01/0</span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">P=</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">). ریسک مقاومت و عدم پاسخ به دارو در گروه </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">e13a2</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> چهار برابر بیشتر از گروه </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">e14a2</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> بود. هیچ تفاوت معنی&shy;داری در بروز تجمعی پاسخ کامل سیتوژنتیکی در بین گروه&shy;های </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">risk score</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> وجود نداشت (05/0</span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">P></span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">). در میان بیماران سیگاری با ترانسکریپت </span></span></span></span></i><i><span dir="LTR" style="font-size:10.0pt"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">e13a2</span></span></span></i><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal"> پاسخ به درمان در مقایسه با غیرسیگاری&shy;ها با همان ترانسکریپت</span></span></span></span></i><span b="" nazanin="" style="font-family:"><span style="font-weight:normal">، </span></span><i><span lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">18بار کمتر بود</span></span></span></span></i><i><span lang="FA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.2pt"><span style="font-weight:normal">.</span></span></span></span></i></span></span></span></span></span></span><br> <b><span dir="RTL" lang="FA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.3pt">نتیجه</span></span></span></b><span dir="RTL" lang="FA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.3pt">&shy;<b>گیری</b><i>:</i></span></span></span> <i><span dir="RTL" lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.3pt">بیماران با ترانسکریپت </span></span></span><b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times=""><span style="letter-spacing:-.3pt">e14a2</span></span></span></b><span dir="RTL" lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.3pt"> مرتبط با پاسخ بهتر و سریعتر به ایماتینیب هستند. </span></span></span><b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times=""><span style="letter-spacing:-.3pt">Sokal risk score</span></span></span></b><span dir="RTL" lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.3pt"> ابزار پیش بینی کننده کارآمدی برای پاسخ مبتنی بر نوع ترانسکریپت نیست. دود سیگار در بیماران بیان کننده </span></span></span><b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times=""><span style="letter-spacing:-.3pt">e13a2</span></span></span></b><span dir="RTL" lang="AR-SA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"><span style="letter-spacing:-.3pt"> ممکن است که مقاومت به درمان را سبب شود.</span></span></span></i> <span style="font-size:12pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:11.0pt"><span new="" roman="" style="font-family:" times=""><b><span style="font-size:11.0pt">Background</span></b><span style="font-size:11.0pt">: In chronic myeloid leukemia (CML), the influence of BCR-ABL1 transcript type, Sokal risk score and smoke on disease phynotype and cytogenetic response to treatment is still unknown and arguable. The objective of this study was to determine the prognostic significance of transcript types, risk score and smoking status among patients with CML treated with different tyrosine kinase inhibitor modalities. </span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:11.0pt"><span new="" roman="" style="font-family:" times=""><b><span style="font-size:11.0pt">Materials and methods</span></b><span style="font-size:11.0pt">: Sixty CML patients were analyzed by Multiplex RT- PCR for molecular typing and banding standard protocols to follow the cytogenetic response of medications at intervals of 3 and 6 months.</span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="line-height:11.0pt"><span new="" roman="" style="font-family:" times=""><b><span style="font-size:11.0pt">Results</span></b><span style="font-size:11.0pt">: The most common transcript type was e14a2 (n=35, 58.3%). There was a significant difference in cumulative incidence (CI) of complete cytogenetic response (CCR) between e14a2 and e13a2 groups (P=0.04). The time to achieve CCR was shorter in e14a2 transcript (P=0.01). The risk of resistance to drug was 4 fold higher in e13a2 group compared to e14a2. No difference was observed in CI of CCR between risk score groups (P>0.05). In smoker patients with e13a2 transcript, response to drug was lower (18 fold) than to non- smokers. </span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:11.0pt"><span new="" roman="" style="font-family:" times=""><b><span style="font-size:11.0pt">Conclusion</span></b><span style="font-size:11.0pt">: The patients with e14a2 transcript may be associated with better and faster response to imatinib. Sokal risk score is not an efficient predictive tool for response based on transcript type. The smoke in patients expressing e13a2 may be induce resistance.</span></span></span></span></span></span><br> &nbsp; ترانسکریپت BCR-ABL1, لوسمی میلوئیدی مزمن, Sokal score, پاسخ کامل سیتوژنتیکی, مهار کننده BCR-ABL transcript, Chronic myeloid leukemia, Sokal risk score, Complete cytogenetic response, TKI, Smoke 139 148 http://tmuj.iautmu.ac.ir/browse.php?a_code=A-10-1456-1&slc_lang=fa&sid=1 Dariush Radin داریوش رادین 100319475328460010457 100319475328460010457 No PhD Student, Department of biology,Marvdasht branch,Islamic azad university,Marvdasht,Iran دانشجوی دکتری، گروه زیست شناسی، واحد مرودشت، دانشگاه آزاد اسلامی ، مرودشت، ایران Mohammad Hamid محمد حمید hamid143@yahoo.com 100319475328460010458 100319475328460010458 Yes Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran گروه پزشکی مولکولی، مرکز تحقیقات بیوتکنولوژی، انستیتو پاستور ایران، تهران، ایران Mohammad Kargar محمد کارگر 100319475328460010459 100319475328460010459 No Department of Microbiology, Jahrom Branch, Islamic Azad University, Jahrom, Iran گروه میکروبیولوژی، دانشگاه آزاد اسلامی واحد جهرم، جهرم، ایران Mojtaba Jafarinia مجتبی جعفری نیا 100319475328460010460 100319475328460010460 No Department of biology,Marvdasht branch,Islamic azad university,Marvdasht,Iran گروه زیست شناسی، واحد مرودشت ،دانشگاه آزاد اسلامی ، مرودشت، ایران