ﺎﺑ ﯽﺘﯿﺳﻮﻠﯿﻣوﺮﭘ دﺎﺣ ﯽﻤﺳﻮﻟ نارﺎﻤﯿﺑ رد Fas ﺮﯿﺴﻣ زا ﺲﯾزﻮﺘﭘﻮﭘآ یﺎﻘﻟا رد ﮏﯿﻨﺳرا ﺶﻘﻧ t (15-17)ﯽﻣوزﻮﻣوﺮﮐ ﯽﯾﺎﺟﻪﺑﺎﺟ
I ﺪﻨﻤﺟرا ﺎﺿﺮﯿﻠﻋ*
II ﺮﮐاذ دﺎﻫﺮﻓ ﺮﺘﮐد
III مﺪﻘﻣﯽﻠﻋ ناﺮﻣﺎﮐ ﺮﺘﮐد
IV هدازماﻮﻗ ﺮﯿﺷدرا ﺮﺘﮐد
V یﺰﻌﻣ ﯽﻠﯿﻟ
هﺪﯿﮑﭼ
نارﺎـﻤﯿﺑ %10-15 رد ﻪـﮐ ﺖــﺳا یﺪﯿﯾﻮﻠﯿﻣ دﺎﺣ ﯽﻤﺳﻮﻟ یﺎﻫهوﺮﮔ ﺮﯾز زا ﯽﮑﯾ ﯽﺘﯿﺳﻮﻠﯿﻣوﺮﭘ دﺎﺣ ﯽﻤﺳﻮﻟ (ATRA)ﺪﯿــﺳا ﮏﯿﯾﻮﻨﯿﺗر ﺲﻧاﺮﺗلآ ﺎﺑ دراﺪﻧﺎﺘﺳا نﺎﻣرد ﺖﺤﺗ ﻪﮐ نارﺎﻤﯿﺑ ﻦﯾا زا %20-30 دوﺪﺣ .ﺪﻫدﯽﻣ خر ﺐﺒﺳ ﺪﻧاﻮﺗﯽﻣ ﯽﯾﺎﻬﻨﺗ ﻪﺑ (ATO)ﮏﯿﻨﺳرا ﺪﯿﺴﮐایﺮﺗ .ﺪﻧﻮﺷﯽﻣ دﻮﻋ رﺎﭼد لﺎﺳ 1 زا ﺮﺗﻢﮐ رد ،ﺪﻧﺮﯿﮔﯽﻣ راﺮﻗ رد نﺎـﻘﻘﺤﻣ تﺎـﻌﻟﺎﻄﻣ .دﻮـﺷ دﻮـﻋ رﺎـﭼد ﺎــﯾ نﺎﻣرد ﻪﺑ موﺎﻘﻣ نارﺎﻤﯿﺑ رد ﯽﺘﺣ ،یرﺎﻤﯿﺑ ﻞﻣﺎﮐ ﺖﻓرﺲﭘ یﺎﻘﻟا ﺺﺨـﺸﻣ رﻮـﻃ ﻪـﺑ ﮏﯿﻨــﺳرا ﻪﮐ داد نﺎﺸﻧ ﯽﻨﯿﻟﺎﺑ یﺎﻫﺦﺳﺎﭘ ﻦﯾا دﺮﮐﻞﻤﻋ یﺎﻫﻢﺴﯿﻧﺎﮑﻣ ندﺮﮐ ﺺﺨﺸﻣ ﺖﻬﺟ ار ﻻﺎﺑ زود ﺎﺑ ﺲﯾزﻮﺘﭘﻮﭘآ یﺎﻘﻟا و ﻦﯿﯾﺎﭘ زود ﺎﺑ ﺰﯾﺎﻤﺗ یﺎﻘﻟا صﻮﺼﺧ ﻪﺑ ﯽﻟﻮﻠﺳ ﻞﺧاد ﯽﻧﺎﺳرمﺎﯿﭘ یﺎﻫﺮﯿﺴﻣ ترﻮـﺻ نارﺎـﻤﯿﺑ ﻦـﯾا یﺎﻫلﻮﻠــﺳ رد ﻢﯿﻘﺘﺴﻣ رﻮﻃ ﻪﺑ ﺲﯾزﻮﺘﭘﻮﭘآ ﯽﺳرﺮﺑ نﻮﻨﮐﺎﺗ .ﺪﻫدﯽﻣ راﺮﻗ ﺮﯿﺛﺄﺗ ﺖﺤﺗ هﺪـﻨﻫد نﺎــﺸﻧ هﺪﻤﻋ رﻮﻃ ﻪﺑ ﻪﮐ ﮏﯿﻤﺳﻮﻟ ﯽﻟﻮﻠﺳ یﺎﻫهدر یور هﺪﺷ مﺎﺠﻧا تﺎﻌﻟﺎﻄﻣ فﻼﺧﺮﺑ و ﺖﺳا ﻪﺘﻓﺮﮕﻧ ATO ﺎـﺑ نﺎـﻣرد لﻮـﻃ رد ﺲـﯾزﻮﺘﭘﻮﭘآ ﮏﯿﺳﻼﮐ یﺎﻫهﺪﻧﺮﯿﮔ زا ﯽﮑﯾ ناﻮﻨﻋ ﻪﺑ Fas/Apo 1 نﺎﯿﺑ ﺮﯿﯿﻐﺗ مﺪﻋ ﻖـﯿﻘﺤﺗ رد .ﺖــﺳا هﺪﺸﻧ ﯽﺳرﺮﺑ نارﺎﻤﯿﺑ رد ﻢﯿﻘﺘﺴﻣ رﻮﻃ ﻪﺑ ﺲﯾزﻮﺘﭘﻮﭘآ هﺪﻧﺮﯿﮔ ﻦﯾا زوﺮﺑ رد ﺮﯿﯿﻐﺗ ،ﺪﻨﺘﺴﻫ یﺮﺘﻣﻮﺘﯾﺎﺳﻮﻠﻓ شور ﮏﯾ زا ،نارﺎﻤﯿﺑ ﻦﯾا ﻢﯿﺧﺪﺑ یﺎﻫلﻮﻠﺳ رد ﺲﯾزﻮﺘﭘﻮﭘآ یﻮﮕﻟا ﯽﺳرﺮﺑ رﻮﻈﻨﻣ ﻪﺑ ﺮﺿﺎﺣ ﺖـﯿﻌﻤﺟ رد ﻪــﮐ یرﻮﻃ ﻪﺑ ؛ﺪﺷ هدﺎﻔﺘﺳا ﮏﯿﺗﻮﺘﭘﻮﭘآ ﮏﯿﻤﺳﻮﻟ یﺎﻫلﻮﻠﺳ ﯽﯾﺎﺳﺎﻨﺷ ﺖﻬﺟ یرﺰﯿﻟ ﮏﺗ و ﮓﻧر 3 ﻪــﯿﻟوا یﺎﻫﺖﯿﻌﻤﺟ 7-AAD و Annexin V شور زا هدﺎﻔﺘﺳا ﺎﺑ ،نارﺎﻤﯿﺑ ناﻮﺨﺘﺳا ﺰﻐﻣ یﺎﻫلﻮﻠﺳ ﻦﮕﻤﻫﺎﻧ درﻮـﻣ ﮏﯿﻤـﺳﻮﻟ ﺖـﯿﻌﻤﺟ رد Fas/Apo I نﺎـﯿﺑ ﺰﯿــﻧ یﺮﮕﯾد ﻞﻧﺎﭘ رد و ﺪﺷ ﯽﯾﺎﺳﺎﻨﺷ ﺲﯾزﻮﺘﭘﻮﭘآ ﯽﯾﺎﻬﺘﻧا و مود ﺎـﺗ لوا یﺎﻫﻪـﺘﻔﻫ رد ﺲـﯾزﻮﺘﭘﻮــﭘآ ناﺰﯿﻣ ﻦﯾﺮﺗﺶﯿﺑ ،هﺪﻣآ ﺖﺳد ﻪﺑ ﺞﯾﺎﺘﻧ سﺎﺳاﺮﺑ .ﺖﻓﺮﮔ راﺮﻗ ﯽﺑﺎﯾزرا ﺎـﻘﻟا ﺲـﯾزﻮﺘﭘﻮـﭘآ ﻪـﮐ ﯽﻧﺎـﻣز رد نارﺎـﻤﯿﺑ ﻦـﯾا ﻢــﯿﺧﺪﺑ یﺎﻫلﻮﻠﺳ رد Fas نﺎﯿﺑ و دﻮﺷﯽﻣ ﯽﯾﺎﺳﺎﻨﺷ نﺎﻣرد .ﺪﺷﺎﺑﯽﻣ ﯽﻟﻮﻠﺳ هﺪﺷ یﺰﯾرﻪﻣﺎﻧﺮﺑ گﺮﻣ یﺎﻘﻟا رد هﺪﻧﺮﯿﮔ ﻦﯾا ﺖﮐﺮﺷ هﺪﻨﻫد نﺎﺸﻧ ،ددﺮﮔﯽﻣ ﺲﯾزﻮﺘﭘﻮﭘآ – 3 ﮏﯿﻨﺳرا ﺪﯿﺴﮐایﺮﺗ – 2 ﯽﺘﯿﺳﻮﻠﯿﻣوﺮﭘ دﺎﺣ ﯽﻤﺳﻮﻟ – 1 :ﺎﻫهژاوﺪﯿﻠﮐ یﺮﺘﻣﻮﺘﯾﺎﺳﻮﻠﻓ – 5 Fas/Apo 1– 4
ناﺮﻣﺎـﮐ ﺮﺘـﮐد هروﺎـﺸﻣ و ﺮـﮐاذ دﺎـﻫﺮﻓ ﺮﺘـﮐد ﯽﯾﺎــﻤﻨﻫار ﻪﺑ ﯽﺳﺎﻨﺷنﻮﺧ ﺪﺷرا ﯽﺳﺎﻨﺷرﺎﮐ ﻪﺟرد ﺖﻓﺎﯾرد ﺖﻬﺟ ﺪﻨﻤﺟرا ﺎﺿﺮﯿﻠﻋ یﺎﻗآ ﻪﻣﺎﻧ نﺎﯾﺎﭘ زا ﺖﺳا یاﻪﺻﻼﺧ ﻪﻟﺎﻘﻣ ﻦﯾا ﯽﮑـﺷﺰﭘ مﻮـﻠﻋ هﺎﮕـﺸﻧاد ﯽﻟﺎـﻣ ﺖﯾﺎـﻤﺣ ﺖــﺤﺗ ﻪﻌﻟﺎﻄﻣ ﻦﯾا .ﺖﺳا هﺪﺷ ﻪﺋارا 1382 لﺎﺳ ناﺮﻬﺗ رد نﺎﻃﺮﺳ ﮏﯿﺘﻧژ ﯽﻠﻠﻤﻟاﻦﯿﺑ ﺶﯾﺎﻤﻫ رد ﻪﻟﺎﻘﻣ ﻦﯾا ﻦﯿﻨﭼﻢﻫ .1382 لﺎﺳ ،مﺪﻘﻣﯽﻠﻋ .(230/1087 :ﺖﺒﺛ هرﺎﻤﺷ)ﺖﺳا هﺪﺷ مﺎﺠﻧا ناﺮﻬﺗ و ﯽﮑـﺷﺰﭘ مﻮـﻠﻋ هﺎﮕـﺸﻧاد ،ﺪـﻤﺣالآلﻼﺟ هاﺮـﮔرﺰـﺑ ،ﯽﺘﻌﯾﺮـﺷ نﺎﺘــﺳرﺎﻤﯿﺑ ،ناﻮﺨﺘﺳا ﺰﻐﻣ ﺪﻧﻮﯿﭘ و یژﻮﻟﻮﮑﻧا و ﯽﺳﺎﻨﺷنﻮﺧ تﺎﻘﯿﻘﺤﺗ ﺰﮐﺮﻣ ،ﯽﺳﺎﻨﺷنﻮﺧ ﺪﺷرا سﺎﻨﺷرﺎﮐ (I (لﻮﺌﺴﻣ ﻒﻟﻮﻣ*).ناﺮﻬﺗ ﯽﻧﺎﻣرد ـ ﯽﺘﺷاﺪﻬﺑ تﺎﻣﺪﺧ .ناﺮﯾا ﯽﻧﺎﻣرد ـ ﯽﺘﺷاﺪﻬﺑ تﺎﻣﺪﺧ و ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ،ﯽﺳﺎﻨﺷنﻮﺧ رﺎﯾدﺎﺘﺳا (II
.ناﺮﻬﺗ ﯽﻧﺎﻣرد ـ ﯽﺘﺷاﺪﻬﺑ تﺎﻣﺪﺧ و ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ،یژﻮﻟﻮﮑﻧا و نﻮﺧ یﺎﻫیرﺎﻤﯿﺑ ﺺﺼﺨﺗقﻮﻓ و رﺎﯾدﺎﺘﺳا (III
.ناﺮﻬﺗ ﯽﻧﺎﻣرد ـ ﯽﺘﺷاﺪﻬﺑ تﺎﻣﺪﺧ و ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ،یژﻮﻟﻮﮑﻧا و نﻮﺧ یﺎﻫیرﺎﻤﯿﺑ ﺺﺼﺨﺗقﻮﻓ و دﺎﺘﺳا (IV
.ناﺮﻬﺗ ﯽﻧﺎﻣرد ـ ﯽﺘﺷاﺪﻬﺑ تﺎﻣﺪﺧ و ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ،ﯽﺳﺎﻨﺷنﻮﺧ ﺪﺷرا سﺎﻨﺷرﺎﮐ (V
ﻪﻣﺪﻘﻣ یﺎـﻫهوﺮﮔ ﺮـﯾز زا ﯽــﮑﯾ (APL)ﯽﺘﯿﺳﻮﻠﯿﻣوﺮﭘ دﺎﺣ ﯽﻤﺳﻮﻟ ﺐــﻠﻏا نآ رد ﻪــﮐ هدﻮــﺑ (AML)یﺪــﯿﯾﻮﻠﯿﻣ دﺎـــﺣ ﯽﻤـﺳﻮﻟ ﻢــﯿﺧﺪﺑ یﺎﻫﺖﯿﺳﻮﻠﯿﻣوﺮﭘ ار نارﺎﻤﯿﺑ ناﻮﺨﺘﺳا ﺰﻐﻣ یﺎﻫلﻮﻠﺳ .ﺪـﻫدﯽﻣ ﻞﯿﮑـﺸﺗ (15؛17)ﯽــﻣوزﻮﻣوﺮﮐ ﯽﯾﺎﺟﻪﺑﺎﺟ ﺺﺧﺎﺷ ﺎﺑ
و 1987 لﺎـﺳ رد (ATRA)ﺪﯿــﺳا ﮏﯿﯾﻮﻨﯿﺗر ﺲﻧاﺮﺗلآ ﯽﻓﺮﻌﻣ
ﻪـــﯾﺎﭘ ﺮــﺑ ﯽﻧﺎــﻣرد ﯽﻤﯿــﺷ ﺎــﺑ ﺐــﯿﮐﺮﺗ رد نآ زا هدﺎﻔﺘــﺳا هﺪﻧﺎـﺳر ﺮﺗﺶﯿﺑ و %70 ﻪﺑ ار نﺎﻣرد رد ﺖﯿﻘﻓﻮﻣ ،ﻦﯿﻠﮑﯾﺎﺳاﺮﺘﻧآ نآ ﺐــﯿﮐﺮﺗ ﺎﯾ ﻦﯿﻠﮑﯾﺎﺳاﺮﺘﻧآ شور ﻪﺑ ﺖﺒﺴﻧ ار ﻪﻟﺎﺳ 5 تﺎﯿﺣ و (1).ﺪﻫد ﺶﯾاﺰﻓا ﺮﺑاﺮﺑ 2 ﻞﻗاﺪﺣ ﻦﯿﺑارﺎﺘﯿﺳ ﺎﺑ رد ﯽـﺒﯿﮐﺮﺗ ترﻮـﺻ ﻪـﺑ ﺎـﯾ ﯽﯾﺎﻬـﻨﺗ ﻪـﺑ ATRA ﺎــﺑ نﺎﻣرد نوﺪـﺑ ﺎـﻣا ﺖــﺳا ﺮﺛﺆﻣ نآ یرادﻪﮕﻧ ﻞﻗاﺪﺣ ﺎﯾ یرﺎﻤﯿﺑ ﺖﻓرﺲﭘ وراد ﻦـﯾا یﺪــﺟ و بﻮﻠﻄﻣﺎﻧ تاﺮﺛا زا ﯽﮑﯾ .ﺖﺴﯿﻧ ﯽﺒﻧﺎﺟ تاﺮﺛا ﺪﻨﻧﺎــﻣ ﯽــﻤﺋﻼﻋ ﺎــﺑ ﻪـــﮐ ﺪـﺷﺎﺑﯽﻣ ﺪﯿـﺳا ﮏـﯿﯾﻮﻨﯿﺗر مرﺪﻨـﺳ ﻞـﯿﻟد ﺎـﺑ ﺐـﺗ ،ﯽـﺴﻔﻨﺗ لﻼـﺘﺧا ﺎـﺑ هاﺮــﻤﻫ ﯽﻧﺎﻬﮔﺎﻧ زﻮﺘﯿﺳﻮﮐﻮﻟ سﺎـﺒﺘﺣا ،نﻮـﺧ رﺎـﺸﻓ ﺶﻫﺎــﮐ ،ﻪﯾر مدا و حﺎﺸﺗرا ،ﺺﺨﺸﻣﺎﻧ نﺎـﺸﻧ ار دﻮـﺧ ﻪـﯿﻠﮐ دﺎــﺣ ﯽﮔدﺎﺘﻓا رﺎﮐ زا و ﺐﻠﻗ و ﺐﻨﺟ هدﺮﭘ ﺮـﮕﯾد یﻮـﺳ زا (3 و2).دﻮـﺷﯽﻣ نارﺎــﻤﯿﺑ ﻦﯾا گﺮﻣ ﺐﺒﺳ و هداد زا یداﺪـﻌﺗ رد یرﺎــﻤﯿﺑ ﺖﺸﮔزﺎﺑ و نﺎﻣرد ﻪﺑ دﺪﺠﻣ ﺦﺳﺎﭘ مﺪﻋ ﺎـﺗ ﺪـﺷ ﺐــﺟﻮﻣ ،ATRA ﺎﺑ نﺎﻣرد ﻪﻣادا ﻊﻄﻗ ﺖﻠﻋ ﻪﺑ نارﺎﻤﯿﺑ ﮏﯿﻨــــﺳرا ﺶــﻘﻧ ﻦــﯿﯿﻌﺗ ﺖﻬــﺟ رد یاهدﺮﺘــﺴﮔ تﺎــﻌﻟﺎﻄﻣ
ﺎــﻫﯽﻨﯿﭼ ﻂﺳﻮﺗ رﺎﺑ ﻦﯿﺘﺴﺨﻧ ﻪﮐ نآ ﺮﯿﺛﺄﺗ و (ATO)ﺪﯿﺴﮐایﺮﺗ
ﺪﯿﯾﺄــﺗ تﺎﻌﻟﺎﻄﻣ دﻮﺟو ﺖﯾﺎﻬﻧ رد .دﺮﯿﮔ ترﻮﺻ ،دﻮﺑ هﺪﺷ ﻪﺋارا ﻦﯾا ﺎﺗ ﺪﺷ ﺐﺒﺳ نآ ﯽﻟﺎﻤﺘﺣا یﺎﻫﻢﺴﯿﻧﺎﮑﻣ ﻪﺋارا ﺎﺑ هاﺮﻤﻫ هﺪﻨﻨﮐ رد APL نارﺎــﻤﯿﺑ نﺎﻣرد رد ﺐﺳﺎﻨﻣ ﯽﯾوراد ناﻮﻨﻋ ﻪﺑ ﺐﯿﮐﺮﺗ (6 و5 ،4).دﺮﯿﮔ راﺮﻗ هدﺎﻔﺘﺳا درﻮﻣ دﺪﺠﻣ دﻮﻋ ﺎﯾ موﺎﻘﻣ دراﻮﻣ هدر ﺮـﺑ ﺐـﯿﮐﺮﺗ ﻦـﯾا ﺮـﺛا هﺪــﺷ ﺪﯿﯾﺎﺗ یﺎﻫﻢﺴﯿﻧﺎﮑﻣ ﻪﻠﻤﺟ زا 0/1-0/5)ﻦﯿﯾﺎـﭘ ﺖــﻈﻠﻏ ﺎﺑ ﺰﯾﺎﻤﺗ یﺎﻘﻟا .NB4 و HL60 ﯽﻟﻮﻠﺳ (لﻮــﻣوﺮﮑﯿﻣ 0/5-2)ﻻﺎﺑ ﺖﻈﻠﻏ ﺎﺑ زﻮﺘﭘﻮﭘآ یﺎﻘﻟا و (لﻮﻣوﺮﮑﯿﻣ ﺰﯿـﻧ و هﺪــﺷ مﺎﺠﻧا هدﺮﺘﺴﮔ تﺎﻘﯿﻘﺤﺗ دﻮﺟو ﺎﺑ (9 و8 ،7).ﺪﺷﺎﺑﯽﻣ زﻮـﺘﭘﻮــﭘآ یﺎﻘﻟا ﺮﯿﺴﻣ ،ﺖﺳا نﺪﺷ مﺎﺠﻧا لﺎﺣ رد ﻪﮐ ﯽﺗﺎﻘﯿﻘﺤﺗ ﻞﻣﺎـﮐ رﻮـﻃ ﻪـﺑ وراد ﻦـﯾا ﻂــﺳﻮﺗ ﺖﯿﺳﻮﻠﯿﻣوﺮﭘ یﺎﻫلﻮﻠﺳ رد ﻞﯿـﺴﻧﺎﺘﭘ ﺶﻫﺎـﮐ رد ﮏﯿﻨــﺳرا ﻢﯿﻘﺘﺴﻣ ﺮﯿﺛﺎﺗ .ﺪﺷﺎﺑﯽﻤﻧ ﻦﺷور
و C موﺮﮐﻮﺘﯿــﺳ یزﺎﺳﺎﻫر نآ لﺎﺒﻧد ﻪﺑ و یرﺪﻨﮐﻮﺘﯿﻣ یﺎﺸﻏ
،9 زﺎﭙــﺳﺎﮐ نﺪﺷ لﺎﻌﻓ ﺖﯾﺎﻬﻧ ردو Apaf-1 ﺎﺑ ﺲﮑﻠﭙﻤﮐ ﻞﯿﮑﺸﺗ ﺮـﺛا لﺎـﺒﻧد ﻪــﺑ ﻪﮐ 8 زﺎﭙﺳﺎﮐ نﺪﺷ لﺎﻌﻓ .ﺖﺳا هﺪﺷ هداد نﺎﺸﻧ ﻖـﯾﺮﻃ زا یرﺪـﻨﮐﻮﺘﯿﻣ یﺎــﺸﻏ ﻞﯿﺴﻧﺎﺘﭘ ﺶﻫﺎﮐ ﺐﺒﺳ وراد ﻦﯾا نﺪـﺷ ﯽــﻃ ﻪﺠﯿﺘﻧ رد و (Bad ﻪﻠﯾرﻮﻔﺴﻓ مﺮﻓ)Bid ندﺮﮐ لﺎﻌﻓ نﺪـﺷ لﺎـﻌﻓ ﻢﯿﻘﺘــﺴﻣﺮﯿﻏ ﺮــﯿﺴﻣ روآدﺎﯾ ،ددﺮﮔﯽﻣ قﻮﻓ ﺮﯿﺴﻣ لدﺎـﻌﻣ ﻪــﭼ ﺮـﮔا (12 و11 ،10)
.ﺪــﺷﺎﺑﯽﻣ ﺰﯿﻧ Fas ﺮﯿﺴﻣ ﯽﻨﻌﯾ نآ دﻮــﺷﯽﻣ ﺰـﯾﻮﺠﺗ ﻪـﮐ یراﺪـﻘﻣ رد وراد ﻦـﯾا In vitro ناﺰﯿـﻣ ﺮـﺑ ﻢﮐﺎـﺣ ﺮﯿـﻐﺘﻣ ﻂﯾاﺮـﺷ ﻪـﺑ ﻪــﺟﻮﺗ ﺎﺑ ،ﺪﻨﮐﯽﻣ ﺎﻘﻟا ار زﻮﺘﭘﻮﭘآ ﻪـﺑ ﯽـﮔدﺎــﺳ ﻪﺑ ار In vitro ﺞﯾﺎﺘﻧ ناﻮﺗﯽﻤﻧ ،In vivo ﻢﺘﺴﯿﺳ یﺎـــﻫلﻮﻠﺳ ﯽــــﯾﺎﺳﺎﻨﺷ ﺮـــﮕﯾد یﻮــــﺳ زا .داد ﺖﺒـﺴﻧ نآ ﻂــﺳﻮﺗ ﺐــﺗﺮﻣ رﻮـﻃ ﻪـﺑ ﻪــﮐ In vivo ﻂـﯿﺤﻣ رد ﮏﯿﺗﻮﺘﭘﻮﭘآ زا ﯽــﮑﯾ ،ﺪﻧﻮـﺷﯽﻣ فﺬـﺣ نﺪـﺑ زا لﺎـﯿﻠﺗوﺪﻧاﻮﻟﻮﮑﯿﺗر ﻢﺘـﺴﯿﺳ ﻪـﻌﻟﺎﻄﻣ ﻞﯿﻟد ﻦــﯿﻤﻫ ﻪﺑ ﺪﯾﺎﺷ و هدﻮﺑ یژﻮﻟﻮﻨﻤﯾا باﺬﺟ ﻞﯾﺎﺴﻣ دﻮـﺟو ﺲــﯾزﻮﺘﭘﻮﭘآ In vivo یﺎﻘﻟا رد وراد ﻦﯾا ﺮﺛا ﻪﻨﯿﻣز رد و Annexin V سﺎــﺴﺣ شور زا هدﺎﻔﺘـﺳا ﻦﯾاﺮﺑﺎـﻨﺑ دراﺪـﻧ
یﺎﻫلﻮﻠـﺳ ﯽﯾﺎــﺳﺎﻨﺷ ﺖﻬﺟ 7-AAD ﺎﺑ نآ نﺎﻣز ﻢﻫ هدﺎﻔﺘﺳا
نژوﺮﺘـﻫ ﺖـﯿﻌﻤﺟ رد زﻮـﺘﭘﻮــﭘآ ﻪﻠﺣﺮﻣ ﻪﺑ هﺪﺷ دراو ﮏﯿﻤﺳﻮﻟ هدﺎﻔﺘﺳا ﺎﺑ ،نارﺎﻤﯿﺑ ناﻮﺨﺘﺳا ﺰﻐﻣ زا هﺪﻣآ ﺖﺳد ﻪﺑ یﺎﻫﻪﻧﻮﻤﻧ ﻪـﺟﻮﺗ ﻞﺑﺎـﻗ ﯽــﮑﯿﻨﮑﺗ تﺎﮑﻧ زا ،ﮓﻧر 3 یﺮﺘﻣﻮﺘﯾﺎﺳﻮﻠﻓ شور زا درﻮـﻣ رد ناﻮـﺗﯽﻣ ،ﻪﺑﺎـﺸﻣ هﺎـﮔﺪـﯾد زا .ﺪـﺷﺎﺑﯽﻣ ﻖــﯿﻘﺤﺗ ﻦﯾا ﺰﯿـﻧ نارﺎـﻤﯿﺑ ﻦـﯾا ﻢـﯿﺧﺪﺑ یﺎﻫلﻮﻠـﺳ رد Fas زوﺮــﺑ تاﺮﯿﯿﻐﺗ لﻮﮑﻟﻮﻣ زوﺮﺑ رد وراد ﻦﯾا ﺶﻘﻧ ﯽﻠﺒﻗ تﺎﻌﻟﺎﻄﻣ رد .ﺖﻔﮔ ﻦﺨﺳ
یﺎـﻘﻟا رد ﯽﻟﻮﻠـﺳ ﺢﻄــﺳ ﮏﯿﺳﻼﮐ یﺎﻫهﺪﻧﺮﯿﮔ زا ﯽﮑﯾ ﻪﮐ Fas
.ﺖﺳا هﺪﺷ شراﺰﮔ ﺾﯿﻘﻧ و ﺪﺿ ترﻮﺻ ﻪﺑ ،ﺪﺷﺎﺑﯽﻣ زﻮﺘﭘﻮﭘآ ﻞﯾﺎــﻗ Fas یاﺮـﺑ ﯽـﺸﻘﻧ ﻪـﮐ یاهﺪـﻤﻋ یﺎـﻫشراﺰﮔ ﻞﺑﺎـﻘﻣ رد ﻦـﯾا ﺖﮐﺮـﺷ ﻪـﮐ یﺪـﯾﺪﺟ یﺎــﻫشراﺰﮔ ﺰﯿﻧ و (13 و12 ،11)
ﺪﻨﺘﺴﯿﻧ ﺮﯿﺛﺎــﺗ ﺖﺤﺗ ار ﯽﻟﻮﻠﺳ هﺪﺷ یﺰﯾرﻪﻣﺎﻧﺮﺑ گﺮﻣ یﺎﻘﻟا رد هﺪﻧﺮﯿﮔ ﻪـﺑ ﺪـﻧاﻮﺗﯽﻤﻧ ﻪـﺘﻓﺎﯾ ﻦـﯾا (14).ﺪـﻧراد دﻮــﺟو ،ﺪﻨﻧادﯽﻣ وراد ﻦﯾا ترﻮـﺻ نﺪـﺑ ﻂـﯿﺤﻣ رد ﻪــﮐ ﺪﺷﺎﺑ ﯽﺗﺎﻗﺎﻔﺗا هﺪﻨﻨﮐ نﺎﯿﺑ ﯽﯾﺎﻬﻨﺗ یﺎﻫلﻮﻠـﺳ ﺖـﯿﻌﻤﺟ رد لﻮـﮑﻟﻮﻣ ﻦـﯾا زوﺮــﺑ ﯽﺳرﺮﺑ و ﻪﺘﻓﺮﮔ ﺖﻬــﺟ رد in vivo ﻂـﯿﺤﻣ رد (CD33)ﯽﺘﯿـﺳﻮﻠﯿﻣوﺮﭘ ﻎﻟﺎـﺑﺎﻧ .ﺪﺳرﯽﻣ ﺮﻈﻧ ﻪﺑ یروﺮﺿ ،قﻮﻓ ﺞﯾﺎﺘﻧ ﺪﯿﯾﺎﺗ ﺎـﺑ هاﺮـﻤﻫ ﺮﺿﺎــﺣ ﻪﻌﻟﺎﻄﻣ رد ،هﺪﺷ ﺮﮐذ ﺐﻟﺎﻄﻣ ﻪﺑ ﻪﺟﻮﺗ ﺎﺑ ﺰـﻐﻣ ﻪـﻧﻮﻤﻧ ﻢـﯿﺧﺪﺑ یﺎﻫلﻮﻠـﺳ ﺖـﯿﻌﻤﺟ رد زﻮــﺘﭘﻮﭘآ ﯽﺳرﺮﺑ
ﮏﯿﻨـﺳرا ﺪﯿـﺴﮐایﺮﺗ ﺎـﺑ نﺎـﻣرد ﺖـﺤﺗ ﻪــﮐ ﯽﻧارﺎﻤﯿﺑ ناﻮﺨﺘﺳا .ﺖﻓﺮﮔ راﺮﻗ ﯽﺑﺎﯾزرا درﻮﻣ ﺰﯿﻧ لﻮﮑﻟﻮﻣ ﻦﯾا زوﺮﺑ ﺮﯿﯿﻐﺗ ،ﺪﻧدﻮﺑ
ﯽﺳرﺮﺑ شور ﻪﺑ ﻪﮐ APL ﻪﺑ ﻼﺘﺒﻣ نارﺎﻤﯿﺑ ﻦﯿﺑ زا رﺎﻤﯿﺑ 3 ﻪﻌﻟﺎﻄﻣ ﻦﯾا رد Reverse)RT-PCR شور ﺎـﺑ و ﺪـﻧدﻮﺑ هﺪــﺷ ﻪﺘﺧﺎﻨﺷ ﯽﮔزﺎﺗ
ﺮـــﻈﻧ زا (transcription-polymerase chain reaction
نﺎـﻣرد ﺖـﺤﺗ و هﺪـﺷ ﺪﯿﯾﺎــﺗ t(15؛17)ﯽﻣوزﻮﻣوﺮﮐ ﯽﯾﺎﺟﻪﺑﺎﺟ زا ﻞﻣﺎـﮐ ﯽﻫﺎــﮔآ ﻦﺘﺷاد ﺎﺑ ،ﺪﻧدﻮﺑ ﻪﺘﻓﺮﮕﻧ راﺮﻗ ﮏﯿﻨﺳرا ﺎﺑ ﯽﻠﺒﻗ ﻪـﻧﻮﻤﻧ .ﺪـﻨﺘﻓﺮﮔ راﺮـﻗ (Case series)ﯽـﺳرﺮﺑ درﻮــﻣ ،ﻪﻌﻟﺎﻄﻣ ﻪـﺑ نﺎـﻣرد عوﺮـﺷ زا نارﺎــﻤﯿﺑ ناﻮﺨﺘﺳا ﺰﻐﻣ زا هﺪﺷ هﺮﯿﭙﺳآ یروآﻊﻤﺟ EDTA دﺎﻘﻌﻧا ﺪﺿ رد ﺖﺑﻮﻧ 3 رد و زور 30 تﺪﻣ شور ﺎﺑ ،ﯽﭘﻮﮑﺳوﺮﮑﯿﻣ ﻪﻌﻟﺎﻄﻣ ﺖﻬﺟ ﺮﯿﻤﺳا ﻪﯿﻬﺗ زا ﺲﭘ و ﺪﺷ ﺎـﺑ یاﻪﺘــﺴﻫﮏﺗ یﺎﻫلﻮﻠﺳ و ﺪﯾدﺮﮔ یﺰﯿﻣآﮓﻧر ﺎﺴﻤﯿﮔ ـ ﺖﯾار ﯽـــﺳرﺮﺑ .ﺪﻧﺪـــﺷ یزﺎــــﺳاﺪﺟ لﻮﮑﯾﺎــﻓ شور زا هدﺎﻔﺘــﺳا ناﻮﺨﺘـﺳا ﺰـﻐﻣ یﺎﻫﻪـﻧﻮﻤﻧ نژوﺮﺘـﻫ ﺖــﯿﻌﻤﺟ رد ﺲﯾزﻮﺘﭘﻮﭘآ Annexin V لﺎﺼﺗا ﺖﯿﺻﺎﺧ سﺎﺳاﺮﺑ و (15)ﯽﻠﺒﻗ شور ﻖﺒﻃ یﺎﻫلﻮﻠـﺳ ﺢﻄﺳ ﻦﯾﺮﺳ ﻞﯾﺪﯿﺗﺎﻔﺴﻓ ﻪﺑ موﺮﮐورﻮﻠﻓ ﺎﺑ ﻪﮔوﮋﻧﻮﮐ ﯽﯾﺎﻬــﺘﻧا و ﻪﯿﻟوا یﺎﻫﺖﯿﻌﻤﺟ ﯽﯾﺎﺳﺎﻨﺷ و ﺪﺷ مﺎﺠﻧا ﮏﯿﺗﻮﺘﭘﻮﭘآ ناﺰﯿـﻣ سﺎـﺳاﺮﺑ و (17 و16)ﻪﺑﺎـﺸﻣ تﺎـﻌﻟﺎﻄﻣ ﻖـﺒﻃ ﮏــﯿﺗﻮﺘﭘﻮﭘآ ﺖﻔﮔ ناﻮﺗﯽﻣ ﻪﺻﻼﺧ رﻮﻃ ﻪﺑ .ﺖﻓﺮﮔ ترﻮﺻ ﻪﺘﺴﻫ ﮓﻧر بﺬﺟ ﻞﯾﺪﯿﺗﺎﻔـﺴﻓ ﺎـﺑ هاﺮـﻤﻫ ﯽـﻌﯿﺒﻃ ﺖﻟﺎــﺣ رد ﻪﮐ ﻦﯾﺮﺳ ﻞﯾﺪﯿﺗﺎﻔﺴﻓ ﺖﻤـﺳ رد Filipase ﻢـﯾﺰﻧآ ﻂــﺳﻮﺗ لﺎﻌﻓ رﻮﻃ ﻪﺑ ﻦﯿﻣآ لﻮﻧﺎﺗا ﻪـﺑ زﻮﺘﭘﻮﭘآ ﯽﯾاﺪﺘﺑا ﻞﺣاﺮﻣ رد ،دﻮﺷﯽﻣ ﻪﺘﺷاد ﻪﮕﻧ ﺎﺸﻏ ﯽﻠﺧاد Annexin V ﻦــﯿﺌﺗوﺮﭘ (18).ﺪﻨﮐﯽﻣ ﺖﮐﺮﺣ ﺎﺸﻏ ﯽﺟرﺎﺧ ﺖﻤﺳ ﻦﯾا ﻪﺑ لﺎﺼﺗا ﯽﯾﺎﻧاﻮﺗ ﯽﯾﻻﺎﺑ ﯽﺒﯿﮐﺮﺗ ﻞﯿﻣ ﺎﺑ ﻢﯿﺴﻠﮐ رﻮﻀﺣ رد ﺖﻬـﺟ ﺺﺧﺎـﺷ ﮏــﯾ ناﻮﻨﻋ ﻪﺑ ﺪﻧاﻮﺗﯽﻣ و ﻪﺘﺷاد ار ﺪﯿﭙﯿﻟﻮﻔﺴﻓ ﺐـﯿﺗﺮﺗ ﻦـﯾﺪﺑ .دور رﺎـﮐ ﻪـﺑ ﮏـﯿﺗﻮﺘﭘﻮــﭘآ یﺎﻫلﻮﻠﺳ ﯽﯾﺎﺳﺎﻨﺷ
ﮓـﻧر رﺎـﻨﮐ رد موﺮـﮐورﻮﻠﻓ ﮏـﯾ ﺎـﺑ ﻪـﮔوﮋــﻧﻮﮐ Annexin V
C-G ﯽﺣاﻮﻧ ﺎﺑ ﻪﮐ (Actinomycin D 7-Amino) 7-AAD
زﻮــﺘﭘﻮﭘآ قاﺮﺘﻓا ﺖﻬﺟ ﺪﻧاﻮﺗﯽﻣ ،دﻮﺷﯽﻣ ﺪﻧﺎﺑ DNA ﻪﺘﺷر ود
راﺮـﻗ هدﺎﻔﺘـﺳا درﻮـﻣ زﻮـﺘﭘﻮـﭘآ ﯽﯾﺎﻬـﺘﻧا ﻪـﻠﺣﺮﻣ ﺎــﯾ زوﺮﮑﻧ زا یﺎﻫلﻮﻠـﺳ قاﺮﺘﻓا ﻞﯿﻟد ﻪﺑ شور ﻦﯾا ﺖﯿﺳﺎﺴﺣ (21 و20 ،19)
.دﺮﯿﮔ ﻪـﺑ ﺖﺒـﺴﻧ نآ شور ندﻮـﺑ ﺮﺗنﺎــﺳآ ،ﮏﯿﺗوﺮﮑﻧ زا ﮏﯿﺗﻮﺘﭘﻮﭘآ ﻞﯿﺴﻧﺎﺘﭘ ﯽﺳرﺮﺑ و ﺎﻫزﺎﭙﺳﺎﮐ ﺖﯿﻟﺎﻌﻓ ﯽﺑﺎﯾزرا ﺪﻨﻧﺎﻣ ﯽﯾﺎﻫشور
نآ ﯽــﯾاﺪﺘﺑا ﻞﺣاﺮﻣ رد هﺪﯾﺪﭘ ﻦﯾا ﯽﯾﺎﺳﺎﻨﺷ ،یرﺪﻨﮐﻮﺘﯿﻣ یﺎﺸﻏ و DNA Ladder ﺪﻨﻧﺎــــﻣ ﯽﯾﺎــــﻫشور ﻪــــﺑ ﺖﺒــــﺴﻧ Terminal oxynucleotide teransferase)TUNEL ﻪﺑ in vivo رد نآ ﯽﺳرﺮﺑ و (dUTP Nick End Labeling رد Biothine ﺎــﺑ ﻪﮔوﮋﻧﻮﮐ Annexin ﯽﻗوﺮﻋ ﻖﯾرﺰﺗ ترﻮﺻ هﺪـﺷ ﺐـﺟﻮﻣ و هدﻮـﺑ شور ﻦــﯾا یﺎﯾاﺰﻣ زا ،ﯽﻧاﻮﯿﺣ یﺎﻫلﺪﻣ ﯽﺑﺎـﯾزرا یﺎـﻫشور ﻦﯾﺮﺘﻬـﺑ زا ﯽــﮑﯾ ناﻮﻨﻋ ﻪﺑ زوﺮﻣا ﺎﺗ ﺖﺳا ﺎــﺑ ﺎﻫلﻮﻠـــﺳ نﻮﯿـﺳﺎﺑﻮﮑﻧا یاﺮـﺑ (22).دور رﺎـﮐ ﻪـﺑ زﻮـﺘﭘﻮـﭘآ ﯽــﺳرﺮﺑ ﻪﺑ طﻮﺑﺮﻣ ﻪﻧﺎﮔاﺪﺟ ﻞﻧﺎﭘ 2 رد Annexin و یدﺎﺑﯽﺘﻧآ یﺎــﻫیدﺎﺑﯽﺘﻧآ ﺎــﺑ ﺎﻫلﻮﻠـــﺳ یﺰﯿـﻣآﮓﻧر ،Fas و زﻮـﺘﭘﻮـﭘآ ،DAKO ﺖﮐﺮــﺷ زا ﺎـــﻫنآ لﺮﺘـﻨﮐ ﭗـﯿﺗوﺰﯾا و لﺎـﻧﻮﻠﮐﻮﻧﻮﻣ
7-AAD یﺰﯿــﻣآﮓﻧر ،IQ product ﺖﮐﺮﺷ زا Annexin V
زا ﻢﯿــﺴﻠﮐ ﺮﻓﺎـﺑ ﺖﺧﺎـﺳ ﺖﻬـﺟ مزﻻ داﻮـﻣ و ICN ﺖﮐﺮـﺷ زا
:ﺖﻓﺮﮔ ترﻮﺻ Merck ﺖﮐﺮﺷ
ﺖــﯿﻌﻤﺟ رد زﻮـــﺘﭘﻮـﭘآ ﯽـﺳرﺮﺑ ﺖﻬـﺟ :زﻮـﺘﭘﻮـﭘآ ﻞﻧﺎـﭘ - ﺎـﺑ نآ ﯽﯾﺎﻬـﺘﻧا و ﯽـﯾاﺪﺘﺑا ﻞـﺣاﺮﻣ قاﺮﺘــﻓا و ﻢﯿﺧﺪﺑ یﺎﻫلﻮﻠﺳ
-FITC زا ﺮﺘــــﯿﻟوﺮﮑﯿﻣ 50 ،ﮓــﻧر 3 یﺮﺘﻣﻮﺘﯾﺎــﺳﻮﻠﻓ شور
ﻞﺑﺎـﻘﻣ رد ﯽﻟﻮﻠـﺳ نﻮﯿـﺴﻧﺎﭙﺳﻮﺳ ﺮﺘــﯿﻟوﺮﮑﯿﻣ 100 ﺎﺑ CD33
ﻪﻘﯿﻗد 20 تﺪﻣ ﻪﺑ و ﺪﺷ طﻮﻠﺨﻣ IgG1-FITC لﺮﺘﻨﮐ ﭗﯿﺗوﺰﯾا تﺪـﻣ ﻪـﺑ ژﻮﻔﯾﺮﺘﻧﺎــﺳ زا ﺲﭘ .ﺪﯾدﺮﮔ ﻪﺑﻮﮑﻧا ﯽﮑﯾرﺎﺗ و ﺦﯾ یور ﺮﻓﺎـﺑ ﺎـﺑ ﯽـﯾور لﻮـﻠﺤﻣ ﺾــﯾﻮﻌﺗ و 400G بﺎﺘﺷ ﺎﺑ ﻪﻘﯿﻗد 10 و HEPES ﺮﻓﺎﺑ ،ﻢﯾﺪﺳ روﺮﻠﮐ ،ﻢﯿﺴﻠﮐ روﺮﻠﮐ ﻞﻣﺎﺷ ﻪﮐ ﻢﯿﺴﻠﮐ ﺮﻓﺎـﺑ ﻦـﯾا رد ﯽﻟﻮﻠــﺳ بﻮﺳر ،دﻮﺑ 7/4 ﺮﺑاﺮﺑ PH ﺎﺑ ﺮﻄﻘﻣ بآ 20 تﺪـﻣ ﻪـﺑ ﯽﮑﯾرﺎـﺗ رد و ﺦـﯾ یور نﻮﯿـﺳﺎﺑﻮﮑﻧا و ﺪــﺷ ﻞﺣ زا هدﺎﻔﺘــﺳا ﺎﺑ نﺎﯾﺎﭘ رد .ﺖﻓﺎﯾ ﻪﻣادا Annexin V-PE ﺎﺑ ﻪﻘﯿﻗد ﺮﻓﺎـﺑ رد ﺮﺘـﯿﻟﯽﻠﯿﻣ رد مﺮـﮔﯽــﻠﯿﻣ 1 ﺖﻈﻠﻏ ﺎﺑ 7-AAD لﻮﻠﺤﻣ ﻪﻠﺻﺎﻓﻼﺑ ﻪﻧﻮﻤﻧ و ﻪﺘﻓﺎﯾ نﺎﯾﺎﭘ یاﻪﻘﯿﻗد 10 نﻮﯿﺳﺎﺑﻮﮑﻧا ،ﻢﯿﺴﻠﮐ .ﺪﺷ هداد هﺎﮕﺘﺳد ﻪﺑ رد Fas(CD95) زوﺮـــﺑ ﯽـــﺳرﺮﺑ ﺖــــﻬﺟ :Fas ﻞﻧﺎــﭘ ـ
،ﮓـﻧر 2 یﺮﺘﻣﻮﺘﯾﺎـﺳﻮﻠﻓ شور ﺎــﺑ CD33+ یﺎﻫلﻮﻠﺳ ﺖﯿﻌﻤﺟ
و CD33-FITC و CD95-PE یﺎـــﻫیدﺎﺑﯽﺘﻧآ زا ﯽـﻃﻮﻠﺨﻣ ﯽــﻔﻨﻣ لﺮﺘﻨﮐ ﭗﯿﺗوﺰﯾا ناﻮﻨﻋ ﻪﺑ IgG1-FITC/IgG1-PE ﺰﯿﻧ ﺮﺘـﯿﻟوﺮﮑﯿﻣ 100 ﺎـﺑ ﮏـﯾ ﺮـﻫ زا ﺮﺘــﯿﻟوﺮﮑﯿﻣ 50 ناﺰﯿﻣ ﻪﺑ ﺎﻫنآ
شرﺎﻤـﺷ ﺎــﺑ لﻮﮑﯾﺎﻓ شور ﺎﺑ هﺪﺷ اﺪﺟ ﯽﻟﻮﻠﺳ نﻮﯿﺴﻧﺎﭙﺳﻮﺳ ﺦــﯾ یور ﻪﻘﯿﻗد 20 تﺪﻣ ﻪﺑ و ﺪﺷ طﻮﻠﺨﻣ ﺮﺘﯿﻟوﺮﮑﯿﻣ رد 4000 .ﺪﯾدﺮﮔ ﻪﺑﻮﮑﻧا ﯽﮑﯾرﺎﺗ رد و
ﺞﯾﺎﺘﻧ ﺪـﻧور ﮏــﯾ ،ناﻮﺨﺘﺳا ﺰﻐﻣ یﺎﻫﻪﻧﻮﻤﻧ ﯽﭘﻮﮑﺳوﺮﮑﯿﻣ ﻪﻌﻟﺎﻄﻣ ﻪـﮐ یرﻮـﻃ ﻪــﺑ داد نﺎﺸﻧ ار ﯽﺘﯿﺳﻮﻠﯿﻣوﺮﭘ یﺎﻫلﻮﻠﺳ رد غﻮﻠﺑ ﻞﺑﺎــﻗ رﻮـــﻃ ﻪـﺑ ﺎﻫﺖﯿـﺳﻮﻠﯿﻣوﺮﭘ ناﺰﯿـﻣ زور 15-20 زا ﺲـﭘ ،ﺖﯿـــﺳﻮﻠﯿﻣ ﺪﻨﻧﺎــــﻣ ﻎﻟﺎــﺑ یﺎﻫلﻮﻠــﺳ و ﺶﻫﺎــﮐ یاﻪــﺟﻮﺗ .دﻮـﺑ ﻪـﺘﻓﺎﯾ ﺶـﯾاﺰﻓا یﺮﯿـﮔﻢــﺸﭼ رﻮﻃ ﻪﺑ ﺪﻧﺎﺑ و ﺖﯿﺳﻮﻠﯿﻣﺎﺘﻣ ﯽــﭘﻮﮑــﺳوﺮﮑﯿﻣ ﻪــﻌﻟﺎﻄﻣ رد ﺰﯿــﻧ ﮏـــﯿﺗﻮﺘﭘﻮـﭘآ یﺎﻫلﻮﻠـﺳ اﺪـﺟ یﺎﻫﻪـﻧﻮﻤﻧ و ناﻮﺨﺘـﺳا ﺰـﻐﻣ ،ﯽــﻄﯿﺤﻣ نﻮﺧ یﺎﻫﺪﯾﻼﺳا
،ﻒـﻟا -1 هرﺎﻤﺷ ﺮﯾﻮﺼﺗ).ﺪﻧﺪﺷ ﯽﯾﺎﺳﺎﻨﺷ ﯽﺑﻮﺧ ﻪﺑ لﻮﮑﯾﺎﻓ ﺎﺑ هﺪﺷ
.(ج و ب
نﻮﺧ ﻪﻧﻮﻤﻧ رد :ﻒﻟا ﮏﯿﺗﻮﺘﭘﻮﭘآ یﺎﻫلﻮﻠﺳ هﺪﻫﺎﺸﻣ :1 هرﺎﻤﺷ ﺮﯾﻮﺼﺗ
ناﻮﺨﺘﺳا ﺰﻐﻣ ﻪﻧﻮﻤﻧ رد :ب،ﯽﻄﯿﺤﻣ ﺰﻐﻣ ﻪﻧﻮﻤﻧ رد ﮏﯿﺗﻮﺘﭘﻮﭘآ یﺎﻫلﻮﻠﺳ هﺪﻫﺎﺸﻣ :ج-1 هرﺎﻤﺷ ﺮﯾﻮﺼﺗ
لﻮﮑﯾﺎﻓ ﺎﺑ هﺪﺷ اﺪﺟ ناﻮﺨﺘﺳا
،زﻮـﺘﭘﻮــﭘآ ﺪﺻرد ﻪﺒﺳﺎﺤﻣ ﺖﻬﺟ یﺮﺘﻣﻮﺘﯾﺎﺳﻮﻠﻓ ﻪﻌﻟﺎﻄﻣ رد ﻪــﮐ dual positive یﺎﻫلﻮﻠـــﺳ FL1-FL2 ﻞﻧﺎـﭘ رد اﺪـﺘﺑا ﺪﻧدﻮﺑ زﻮﺘﭘﻮﭘآ زﺎـﻓ ﻪـﺑ هﺪـﺷ دراو ﻢــﯿﺧﺪﺑ یﺎﻫلﻮﻠﺳ هﺪﻨﯾﺎﻤﻧ ﮏـﯿﮑﻔﺗ ﺖﻬـﺟ FL2-FL3 ﻞﻧﺎـﭘ ردو (gatting)ﺪﻧﺪــﺷ بﺎﺨﺘﻧا راﺮــــﻗ ﯽــﺳرﺮﺑ درﻮـﻣ زﻮـﺘﭘﻮـﭘآ ﯽﯾﺎﻬـﺘﻧا و ﯽـﯾاﺪﺘﺑا ﻞـﺣاﺮﻣ .ﺪـﻨﺘﻓﺮﮔ ﻪـﺑ ﺎﻫﻪﻧﻮﻤﻧ زا یداﺪﻌﺗ رد زﻮﺘﭘﻮﭘآ ﻪــﯿﻟوا ﺖــﯿﻌﻤﺟ ﻪﭼ ﺮﮔا عﻮــﻧ ﺐﺴﺣﺮﺑ ،دﻮﺑ هﺪﺷ دراو ﺲﯾزﻮﺘﭘﻮﭘآ ﯽﯾﺎﻬﺘﻧا ﻪﯿﺣﺎﻧ ﻞﺧاد رﻮــﺒﻋ نﺎﻣز تﺪﻣ ﺰﯿﻧ و In vivo ﻂﯿﺤﻣ رد هﺪﺷ مﺎﺠﻧا ﻪﻌﻟﺎﻄﻣ ﻪـــﻠﺣﺮﻣ ﻪـﺑ (Annexin+-7AAD-)ﯽـﯾاﺪﺘﺑا ﻪـﻠﺣﺮﻣ زا لﻮﻠـﺳ 1 ضﺮـﻋ رد ﺎﻬـﻨﺗ ﻪــﮐ زﻮﺘﭘﻮﭘآ (Annexin+-7AAD+)ﯽﯾﺎﻬﺘﻧا ﺪــﻧور ﻞـــﮐ ﯽــــﺘﺣ و دﺮــــﯿﮔ ترﻮــﺻ ﺪـــﻧاﻮﺗﯽﻣ ﺖﻋﺎـﺳ ﻦـــﯿﻟوا ،ﺪـﻫد خر ﺮـــﺗﻊﯾﺮﺳ ﻢـﻫ زﻮـﺘﯿﻣ ﮏـﯾ زا ﺲـﯾزﻮﺘﭘﻮـﭘآ ﻪــﯿﻟوا ﻞﺣاﺮﻣ رد زﻮﺘﭘﻮﭘآ زﺎﻓ ﻪﺑ هﺪﺷ دراو یﺎﻫلﻮﻠﺳ ،ﺖﯿﻌﻤﺟ تﺪـﺷ ﺮـﻈﻧ زا ﻪـﮐ مود ﺖـﯿﻌﻤﺟ و (early)ﻪـﯿﻟوا رﺎــﺼﺘﺧا ﻪﺑ
ﻪـﺑ هﺪـﺷ دراو یﺎﻫلﻮﻠــﺳ ،دﻮﺑ ﺮﺗﺶﯿﺑ 7AAD ﺲــﻧﺎﺳرﻮﻠﻓ
ﺮـﯾﻮﺼﺗ)ﺪـﺷ هﺪﯿﻣﺎـﻧ (late)نآ ﯽﯾﺎﻬـﺘﻧا ﻞــﺣاﺮﻣ رد زﻮﺘﭘﻮﭘآ زﺎﻓ .(2 هرﺎﻤﺷ
یﺎﻫلﻮﻠــﺳ ﺪـﺻرد عﻮـﻤﺠﻣ زا هﺪـﻣآ ﺖــﺳد ﻪـــﺑ ﺞـــﯾﺎﺘﻧ عﻮـــﻗو ،نارﺎـــﻤﯿﺑ رد ﺲـــﯾزﻮﺘﭘﻮــﭘآ ﯽـــــﯾﺎﻬﺘﻧا و ﻪـــﯿﻟوا نﺎـــﺸﻧ ار نﺎـــﻣرد ﻂــــﺳاوا و ﻞــﯾاوا رد ﻻﺎﺑ ﺲـﯾزﻮﺘﭘﻮﭘآ .داد
ﺖـﯿﻌﻤﺟ 2 (gatting)بﺎـﺨﺘﻧا ﺎــﺑ ﺲﯾزﻮﺘﭘﻮﭘآ ﯽﺑﺎﺨﺘﻧا یﺎﻘﻟا ﯽﯾﺎــــــﺳﺎﻨﺷ و CD33--Annexin- و CD33+-Annexin+
درﻮــﻣ نآ (Dot Plot)یاﻪﻄﻘﻧ رادﻮﻤﻧ رد ﻪﻃﻮﺑﺮﻣ یﺎﻫﺖﯿﻌﻤﺟ
3 هرﺎﻤـــﺷ ﺮـﯾﻮﺼﺗ رد ﻪـﮐ رﻮﻃنﺎـﻤﻫ .ﺖـﻓﺮﮔ راﺮـﻗ ﯽـﺳرﺮﺑ رد ﻪﻧ و ﻢﯿﺧﺪﺑ ﺖﯿﻌﻤﺟ رد ﺲﯾزﻮﺘﭘﻮﭘآ یﺎﻘﻟا دﻮﺷﯽﻣ هﺪﻫﺎﺸﻣ ﻦـﯾا ﯽﺑﺎـﺨﺘﻧا ﺮــﺛا ﯽﺑﻮﺧ ﻪﺑ ﺰﻐﻣ یﺎﻫلﻮﻠﺳ ﯽﺘﯿﺳﻮﻔﻨﻟ ﺖﯿﻌﻤﺟ
Fas ﻞﻧﺎـﭘ رد .ﺪـﻫدﯽﻣ نﺎــﺸﻧ ﻢﯿﺧﺪﺑ یﺎﻫلﻮﻠﺳ یور ار وراد
یﺎﻫلﻮﻠـﺳ هﺪﻨﯾﺎــﻤﻧ ﻪﮐ Dual positive یﺎﻫلﻮﻠﺳ ﺪﺻرد ﺰﯿﻧ
ﺪـــﻧور ﺎــــﺑ و ﺪــﺷ ﻪﺒــﺳﺎﺤﻣ ،ﺪﻨﺘــﺴﻫ CD95+ و CD33+
تاﺮﯿـﯿﻐﺗ رﺎـﻤﯿﺑ 2 رد .ﺖـﻓﺮﮔ راﺮـﻗ ﻪــﻌﻟﺎﻄﻣ درﻮﻣ ﺲﯾزﻮﺘﭘﻮﭘآ تاﺮﯿـﯿﻐﺗ ﺎـﺑ مﺎـﮕﻤﻫ ،ﻢـﯿﺧﺪﺑ یﺎﻫلﻮﻠــﺳ ﺖﯿﻌﻤﺟ رد Fas نﺎﯿﺑ ﻦـﯾا نارﺎـﻤﯿﺑ زا ﯽـﮑﯾ رد ﺎﻬـﻨﺗ و ﺖـﺷاد ﯽﮕﻨﻫﺎﻤﻫ ﺲﯾزﻮﺘﭘﻮﭘآ .(1 هرﺎﻤﺷ رادﻮﻤﻧ)دﻮﺒﻧ ﺲﯾزﻮﺘﭘﻮﭘآ تاﺮﯿﯿﻐﺗ ﺎﺑ ﮓﻨﻫﺎﻤﻫ تاﺮﯿﯿﻐﺗ
بﺎﺨﺘﻧا .ﺲﯾزﻮﺘﭘﻮﭘآ یﺎﻘﻟا رد ﮏﯿﻨﺳرا ﯽﺑﺎﺨﺘﻧا ﺮﺛا -3 هرﺎﻤﺷ ﺮﯾﻮﺼﺗ
ﺎﺑ ﺎﻫنآ ﯽﯾﺎﺳﺎﻨﺷ و ﻒﻟا رادﻮﻤﻧ رد ﮏﯿﺗﻮﺘﭘﻮﭘآﺮﯿﻏ و ﮏﯿﺗﻮﺘﭘﻮﭘآ ﺖﯿﻌﻤﺟ 2 .ب رادﻮﻤﻧ رد .ﻪﻧﻮﻤﻧ نﺎﻤﻫ Dot plot رادﻮﻤﻧ رد هﺪﺷ ﺮﮐذ ﻪﯿﺣﺎﻧ 2 ﻒﯾﺮﻌﺗ و هدﺮﮐ زﻮﺘﭘﻮﭘآ زﺎﻓ دراو ار ﻢﯿﺧﺪﺑ یﺎﻫلﻮﻠﺳ ﯽﺑﺎﺨﺘﻧا رﻮﻃ ﻪﺑ ﮏﯿﻨﺳرا
.ﺖﺳا ﻪﺘﺷاﺪﻧ ﺮﮕﯾد یﺎﻫلﻮﻠﺳ ﺮﺑ یﺮﺛا
رد ناﻮﺨﺘﺳا ﺰﻐﻣ ﯽﻟاﻮﺘﻣ یﺎﻫﻪﻧﻮﻤﻧ رد زﻮﺘﭘﻮﭘآ زﺎﻓ ﻪﺑ هﺪﺷ دراو ﻢﯿﺧﺪﺑ یﺎﻫلﻮﻠﺳ ﺖﯿﻌﻤﺟ بﺎﺨﺘﻧا هﻮﯿﺷ -2 هرﺎﻤﺷ ﺮﯾﻮﺼﺗ
.نﺎﻣرد ﻞﯾاوا رد هﺪﻤﻋ رﻮﻃ ﻪﺑ زﻮﺘﭘﻮﭘآ یﺎﻬﺘﻧا و اﺪﺘﺑا ﺖﯿﻌﻤﺟ 2 ﯽﯾﺎﺳﺎﻨﺷ و (ج)نﺎﻣرد ﺮﺧآ ،(ب)نﺎﻣرد ﻂﺳو ،(ﻒﻟا)نﺎﻣرد یاﺪﺘﺑا .ﺖﺳا یدﺎﺑﯽﺘﻧآ لﺮﺘﻨﮐ ﭗﯿﺗوﺰﯾا هﺪﻨﻫد نﺎﺸﻧ ﭗﭼ نﻮﺘﺳ
رد Fas نﺎﯿﺑ تاﺮﯿﯿﻐﺗ و ﺲﯾزﻮﺘﭘﻮﭘآ ﯽﺳرﺮﺑ -1 هرﺎﻤﺷ رادﻮﻤﻧ
مود و لوا یﺎﻫﻪﺘﻔﻫ رد ﻪﻌﻟﺎﻄﻣ درﻮﻣ نارﺎﻤﯿﺑ
ﺚﺤﺑ ،APL نارﺎـﻤﯿﺑ رد ﮏﯿﻨـﺳرا ﻂــﺳﻮﺗ ﯽﯾﺎﻘﻟا زﻮﺘﭘﻮﭘآ یﻮﮕﻟا رد نآ ﺶـﻘﻧ ﻪـﮐ ﺎـﺟ نآ زا و ﺖــﺷاﺪﻧ دﻮﺟو ﯽﻠﺒﻗ تﺎﻌﻟﺎﻄﻣ رد in vitro بذﺎﮐ ﻪﺠﯿﺘﻧ ﮏﯾ ﻪﺑ کﻮﮑﺸﻣ In vivo زﻮﺘﭘﻮﭘآ یﺎﻘﻟا ،(23)ﺖـﺳا هﺪـﺷ حﺮــﻄﻣ نآ یاﺮﺑ ﺰﯾﺎﻤﺗ یﺎﻘﻟا ﺶﻘﻧ ﺎﻬﻨﺗ و هدﻮﺑ
ﺮـﻈﻧ ﻪـﺑ یروﺮـﺿ ﮏﯿﻨـﺳرا In vivo زﻮﺘﭘﻮﭘآ یﺎﻘﻟا ﯽﺳرﺮﺑ
ﻢﺘـﺴﯿﺳ ﺮـﻫ توﺎــﻔﺘﻣ و ﺮﯿﻐﺘﻣ ﻂﯾاﺮﺷ ﺮﮕﯾد یﻮﺳ زا .ﺪﺳرﯽﻣ یاﻪـﻌﻟﺎﻄﻣ ﻪـﺑ ار ﻢﺘـﺴﯿﺳ ﻦــﯾا رد زﻮﺘﭘﻮﭘآ ﯽﺳرﺮﺑ ،In vivo
ﺎـﺑ ﻪـﮔوﮋـﻧﻮﮐ Annexin V ﻖﯾرﺰﺗ .ﺖﺳا هدﺮﮐ ﻞﯾﺪﺒﺗ هﺪﯿﭽﯿﭘ
ﺎـﺑ ﮏـﯿﺗﻮﺘﭘﻮـﭘآ یﺎﻫلﻮﻠـﺳ ﯽﯾﺎـﺳﺎﻨﺷ و شﻮــﻣ ﻪﺑ Biothine
ﻖــــﯾرﺰﺗ و (24)موﺮــﮐورﻮﻠﻓ ﺎــﺑ ﻪــﮔوﮋــﻧﻮﮐ streptavidine رد ﺎــﻫنآ ﯽﺑﺎﯾدر و ﻮﯿﺘﮐاﻮﯾدار داﻮﻣ ﺎﺑ ﻪﮔوﮋﻧﻮﮐ Annexin V ﻪـﮐ ﺪﻨﺘـﺴﻫ زﻮـﺘﭘﻮﭘآ In vivo تﺎﻌﻟﺎﻄﻣ ﻪﻠﻤﺟ زا (25)شﻮﻣ نﺪﺑ .ﺪﻨﺷﺎﺑﯽﻤﻧ نﺎﺴﻧا رد اﺮﺟا ﻞﺑﺎﻗ ناﻮﺨﺘﺳا ﺰﻐﻣ یﺎﻫﻪﻧﻮﻤﻧ رد ﮏﯿﺗﻮﺘﭘﻮﭘآ یﺎﻫلﻮﻠﺳ هﺪﻫﺎﺸﻣ ﯽﯾﺎﻬـﺘﻧا و ﯽـﯾاﺪﺘﺑا ﻞـﺣاﺮﻣ ﯽﯾﺎـﺳﺎﻨﺷ ﺰﯿـﻧ و ﯽــﻄﯿﺤﻣ نﻮﺧ و
رد 7-AAD و Annexin V سﺎـﺴﺣ شور ﺎــﺑ ﺲﯾزﻮﺘﭘﻮﭘآ
ﯽـﻌﻄﻗ ﺶـﻘﻧ هﺪـﻨﻫد نﺎـﺸﻧ نارﺎــﻤﯿﺑ ناﻮﺨﺘﺳا ﺰﻐﻣ یﺎﻫﻪﻧﻮﻤﻧ
.ﺪﺷﺎﺑﯽﻣ ﺲﯾزﻮﺘﭘﻮﭘآ یﺎﻘﻟا رد ATO
ﺪــﺻرد ﻪﮐ ﯽﻧﺎﻣز ،نﺎﻣرد ﻞﯾاوا رد ﺲﯾزﻮﺘﭘﻮﭘآ یﻻﺎﺑ ﺪﻧور ﺢــﺿاو زﻮﺘﭘﻮﭘآ ﯽﯾﺎﺳﺎﻨﺷ و ﺪﺑﺎﯾﯽﻣ ﺶﯾاﺰﻓا ﻢﯿﺧﺪﺑ یﺎﻫلﻮﻠﺳ رﻮـﻃ ﻪــﺑ ،(ﯽﺘﯿﺳﻮﻔﻨﻟ ﺖﯿﻌﻤﺟ ﻪﻧ) ﻢﯿﺧﺪﺑ یﺎﻫلﻮﻠﺳ ﺖﯿﻌﻤﺟ رد یﺎـﻘﻟا رد ﮏﯿﻨـﺳرا ﯽﺑﺎـﺨﺘﻧا ﺮـﺛا In vitro تﺎــﻌﻟﺎﻄﻣ ﯽﺒﺳﺎﻨﻣ ﻪﺑ ﺎﯿﺣا نﻮﯿﺗﺎﺗﻮﻠﮔ ﺢﻄﺳ ﺶﻫﺎﮐ .ﺪﻨﮐﯽﻣ ﺪﯿﯾﺎﺗ ار (25)ﺲﯾزﻮﺘﭘﻮﭘآ زاﺪﯿـﺴﮐاﺮﭘ نﻮﯿﺗﺎــﺗﻮﻠﮔ و زﻻﺎﺗﺎﮐ یﺎﻫﻢﯾﺰﻧآ ﺢﻄﺳ ﺶﻫﺎﮐ ﻞﯿﻟد و (26)ﺎﻫلﻮﻠـﺳ ﺮﯾﺎـﺳ ﻪـﺑ ﺖﺒـﺴﻧ ﺖﯿــﺳﻮﻠﯿﻣوﺮﭘ یﺎﻫلﻮﻠﺳ رد ﺖﺒـﺴﻧ ﯽﺘﯿــﺳﻮﻠﯿﻣوﺮﭘ یﺎﻫلﻮﻠﺳ رد ﯽﻟﻮﻠﺳ ﺮﯿﺜﮑﺗ یﻻﺎﺑ ﺪﻧور ﺮـﺛا ﯽﻟﺎـﻤﺘﺣا ﻞــﯾﻻد زا (27)ﯽﻌﯿﺒﻃ یﺎﻫلﻮﻠﺳ و ﺎﻫﺖﯿﺳﻮﻠﯿﻣ ﻪﺑ مزﻻ ﻪـﺘﮑﻧ ﻦــﯾا ﺮﮐذ .ﺪﺷﺎﺑﯽﻣ ﺎﻫلﻮﻠﺳ ﻦﯾا ﺮﺑ ﮏﯿﻨﺳرا ﯽﺑﺎﺨﺘﻧا ﺮـﺑ ATO بﻮﻠﻄﻣﺎـﻧ تاﺮـﺛا در یﺎـﻨﻌﻣ ﻪــﺑ ﺐﻠﻄﻣ ﻦﯾا ﻪﮐ ﺖﺳا ﻪـﻌﻟﺎﻄﻣ ﻪـﺑ زﺎـﯿﻧ دﻮـﺧ و هدﻮـﺒﻧ زﺎــﺳنﻮﺧ یدﺎﯿﻨﺑ یﺎﻫلﻮﻠﺳ .دراد یﺮﮕﯾد زا ،نآ هﺪـﻨﻨﮐ ﺎـﻘﻟا ﺎــﯾ کﺮﺤﻣ سﺎﺳاﺮﺑ زﻮﺘﭘﻮﭘآ ﯽﻠﮐ رﻮﻃ ﻪﺑ ﯽــﻠﺻا ﺮﯿﺴﻣ 2 هزوﺮﻣا .دﺪﻧﻮﯿﭘﯽﻣ عﻮﻗو ﻪﺑ ﯽﻔﻠﺘﺨﻣ یﺎﻫﺮﯿﺴﻣ لﺎـﻌﻓ ﺎـﺑ ﺎــﻫنآ زا ﯽﮑﯾ ﻪﮐ ﺖﺳا هﺪﺷ ﯽﯾﺎﺳﺎﻨﺷ زﻮﺘﭘﻮﭘآ یﺎﻘﻟا
ﺐــﺟﻮﻣ و هﺪﺷ عوﺮﺷ TNFR و Fas گﺮﻣ یﺎﻫهﺪﻧﺮﯿﮔ ندﺮﮐ
نآ لﺎـﺒﻧد ﻪـﺑ ﻪـﮐ دﻮـﺷﯽﻣ FADD ﯽــﮑﻤﮐ لﻮﮑﻟﻮﻣ ﯽﻧاﻮﺧاﺮﻓ
ﻞــﺤﻣ رد ار نآ ،8 زﺎﭙﺳﺎﮐوﺮﭘ ﯽﻧاﻮﺧاﺮﻓ ﺎﺑ هاﺮﻤﻫ ﺰﯿﻧ FADD ﺮﯿـﺴﻣ .ﺪـﻨﮐﯽﻣ ﻪـﯾﺰﺠﺗ لﺎـﻌﻓ 8 زﺎﭙـﺳﺎﮐ ﻪـﺑ هﺪﻧﺮﯿــﮔ ﺲﮑﻠﭙﻤﮐ دﻮﺷ ﺎﻘﻟا ﺪﻧاﻮﺗﯽﻣ ﺎﻫکﺮﺤﻣ زا ﯽﻌﯿﺳو ﻒﯿﻃ ﻂﺳﻮﺗ ﻪﮐ یﺮﮕﯾد رد C موﺮﮐﻮﺘﯿــﺳ یزﺎـــﺳﺎﻫر و یرﺪـﻨﮐﻮﺘﯿﻣ یﺮﯿـﮔرد ﺎـﺑ و یﺎـﻀﻋا ﻂـﺳﻮﺗ ﻪـﮐ ﺖــﺳا یاهﺪﯾﺪﭘ ،ﺪﺷﺎﺑ هاﺮﻤﻫ ﻢﺳﻼﭘﻮﺘﯿﺳ .دﻮﺷﯽﻣ لﺮﺘﻨﮐ Bcl2 هداﻮﻧﺎﺧ ﺎﺑ لﺎﺼﺗا لﺎﺒﻧد ﻪﺑ یرﺪﻨﮐﻮﺘﯿﻣ زا هﺪﺷ ﺎﻫر C موﺮــﮐﻮﺘﯿﺳ و دﻮــــﺷﯽﻣ 9 زﺎﭙــﺳﺎﮐوﺮﭘ نﺪــﺷ لﺎــﻌﻓ ﺐﺒــﺳ ،Apaf -1 یﺮـﺛﻮﻣ یﺎﻫزﺎﭙــﺳﺎﮐ ﻪﺑ مﺎﯿﭘ لﺎﻘﺘﻧا ﺎﺑ 9 و 8 لﺎﻌﻓ یﺎﻫزﺎﭙﺳﺎﮐ .ﺪﻨﻨﮐﯽﻣ لﺎﻌﻓ ار ﺎﻫنآ 7 و 6 و 3 یﺎﻫزﺎﭙﺳﺎﮐ ﺪﻨﻧﺎﻣ نﺎـﻨﭼﻢـﻫ ﮏﯿﻨـﺳرا ﯽــﯾﺎﻘﻟا زﻮـﺘﭘﻮــﭘآ ﯽــﻟﻮﮑﻟﻮﻣ ﻢﺴﯿﻧﺎﮑﻣ ﺐـــﺟﻮﻣ ﯽـــﻫﺎﺗﻮﮐ نﺎـﻣز رد ﮏـــﯿﻨﺳرا .ﺖـﺳا ﺚـﺤﺑ درﻮـﻣ موﺮﮐﻮﺘﯿـﺳ یزﺎــﺳﺎﻫر و یرﺪـﻨﮐﻮﺘﯿﻣ یﺎﺸﻏ ﻞﯿﺴﻧﺎﺘﭘ ﺶﻫﺎﮐ ﻖـــﯾﺮﻃ زا ﺐـــﯿﺗﺮﺗ ﻦـــــﯾﺪﺑ و دﻮـﺷﯽﻣ ﻢـﺳﻼﭘﻮﺘﯿـﺳ ﻪـﺑ C ﻪـﮐ ﺎـﺟ نآ زا .ددﺮـﮔﯽـﻣ زﻮـﺘﭘﻮــﭘآ یﺎﻘﻟا ﺐﺒﺳ مود ﻢﺴﯿﻧﺎﮑﻣ ﯽﯾﺎــﻘﻟا زﻮﺘﭘﻮﭘآ ﺮﺛا رد 3 و 8 لﺎﻌﻓ یﺎﻫزﺎﭙﺳﺎﮐ ﺢـﻄﺳ ﺶﯾاﺰﻓا
یﺎﻫﺮﯿﺴﻣ زا ﯽﮑﯾ Fas ﺮــﯿﺴﻣ و هﺪــﺷ هداد نﺎﺸﻧ ﮏﯿﻨﺳرا ﺎﺑ ﯽـــﻨﯿﺑﺶﯿﭘ ﻞـــﺑﺎﻗ ﻪﻠﺌــﺴﻣ ﻦﯾا .ﺪﺷﺎﺑﯽﻣ 8 زﺎﭙﺳﺎﮐ نﺪﺷ لﺎﻌﻓ گﺮــــﻣ یﺎــﻘﻟا ﺐـــﺒﺳ ﺮﯿــﺴﻣ ﻦـــﯾا زا وراد ﻦـﯾا ﻪـﮐ ﺖـﺳا ﻪـﮐ ﯽﻟﺎـﺣ رد ددﺮــﮔ ﺎــﻫلﻮﻠﺳ ﻦــــﯾا رد هﺪــﺷ یﺰﯾرﻪﻣﺎﻧﺮﺑ هدﻮــﺒﻧ ﯽـﻣاﺰﻟا Fas ﺮــﯿﺴﻣ ﻖـﯾﺮﻃ زا لﺎـﻌﻓ 8 زﺎـﭙﺳﺎﮐ زوﺮـﺑ نﺎــﻣزﻢﻫ لﺎــﺼﺗا ﺪﻨﻧﺎــﻣ یﺮــﮕﯾد هﺪـــﯿﭽﯿﭘ یﺎﻫﻢـﺴﯿﻧﺎﮑﻣ و Tumor Necrosis Factor Receptor)TNFR-ICD30 ﺰﯿـﻧ ﯽﺑﺎــﺗﻮﺗﺮﭘ و ﯽﻧﺎﻣرد ﯽﻤﯿﺷ ،ﻪﻃﻮﺑﺮﻣ یﺎﻫﺪﻧﺎﮕﯿﻟ ﺎﺑ (Type ﺮـﮕﯾد یﻮـﺳ زا (12 و11).ﺪـﻧدﺮﮔ نآ نﺪــﺷ لﺎﻌﻓ ﺐﺒﺳ ﺪﻨﻧاﻮﺗﯽﻣ نارﺎـﻤﯿﺑ ﻦـﯾا نﺎــﻣرد ﻪﺑ ﺦﺳﺎﭘ زا ﻞﺻﺎﺣ توﺎﻔﺘﻣ ﯽﻨﯿﻟﺎﺑ ﺞﯾﺎﺘﻧ یرﻮـﻃ ﻪــﺑ ﺖﺳا یرﺎﻤﯿﺑ ﻦﯾا نژوﺮﺘﻫ ﺖﯿﻫﺎﻣ هﺪﻨﻫد نﺎﺸﻧ ﺰﯿﻧ ،نﺎـﻣرد ﻪــﺑ ﺐﺳﺎﻨﻣ ﺦﺳﺎﭘ نداد ﺎﺑ هاﺮﻤﻫ نارﺎﻤﯿﺑ زا ﯽﻀﻌﺑ ﻪﮐ ضراﻮـﻋ رﺎــﭼد ﻢﻫ یداﺪﻌﺗ ﻞﺑﺎﻘﻣ رد و ﻪﺘﻓر ﻞﻣﺎﮐ ﺖﻓرﺲﭘ ﻪﺑ نﺎــﯿﺑ یاﺮﺑ ﯽﻬﯿﺟﻮﺗ ﺪﻧاﻮﺗﯽﻣ دﻮﺧ ﻪﮐ ﺪﻧﻮﺷﯽﻣ رﺎﺑگﺮﻣ ﯽﺒﻧﺎﺟ .ﺪﺷﺎﺑ نارﺎﻤﯿﺑ ﻦﯾا رد Fas توﺎﻔﺗ گﺮــــﻣ یﺎــﻘﻟا رد Fas ﻪــﮐ داد نﺎــﺸﻧ ﺮﺿﺎــﺣ ﻪــﻌﻟﺎﻄﻣ
ﯽﺗوﺎـﻔﺘﻣ یﻮـﮕﻟا ﺎـﺑ ATO ﻂـﺳﻮﺗ ﯽﻟﻮﻠــﺳ هﺪﺷ یﺰﯾرﻪﻣﺎﻧﺮﺑ
mRNA ﺢﻄـﺳ تاﺮﯿـﯿﻐﺗ ﯽﺑﺎـﯾزرا ﺎــﺑ ﻦﯾاﺮﺑﺎﻨﺑ ﺪﻨﮐﯽﻣ ﺖﮐﺮﺷ
ﺎــﺑ هاﺮـــﻤﻫ هﺪﻧﺮﯿـﮔ ﻦـﯾا نﺎـﯿﺑ ﮏـﯿﻣﻮﻧژ ﯽـﺳرﺮﺑ ﺎـﯾ ﯽﻟﻮﻠـﺳ
ﺪﻨﻧﺎـﻣ ﯽﯾﺎــﻫشور ﺎﺑ FADD ﺪﻨﻧﺎﻣ یﺮﮕﯾد ﺮﺛﻮﻣ یﺎﻫلﻮﮑﻟﻮﻣ
رد هﺪﻧﺮﯿـﮔ ﻦـﯾا ﺶـﻘﻧ ﯽـﮕﻧﻮﮕﭼ ناﻮـﺘﺑ ﺪﯾﺎــﺷ ،Micro array .دﺮﮐ ﯽﯾﺎﺳﺎﻨﺷ ار ﮏﯿﻨﺳرا ﯽﯾﺎﻘﻟا ﺲﯾزﻮﺘﭘﻮﭘآ ﺖﻔﮔ ناﻮﺗﯽﻣ هﺪﻣآ ﺖﺳد ﻪﺑ ﺞﯾﺎﺘﻧ سﺎﺳاﺮﺑ ﻪﺻﻼﺧ رﻮﻃ ﻪﺑ یﺎﻫلﻮﻠـﺳ رد ﯽﺑﺎـﺨﺘﻧا ترﻮـﺻ ﻪـﺑ ﺪﯿـﺴﮐایﺮﺗ ﮏﯿﻨــﺳرا ﻪﮐ ﻂﯾاﺮــﺷ ﺎﻣا دﻮﺷﯽﻣ زﻮﺘﭘﻮﭘآ یﺎﻘﻟا ﺐﺒﺳ APL نارﺎﻤﯿﺑ ﻢﯿﺧﺪﺑ ﯽﺻﺎــﺼﺘﺧا ﮏﯿﺘﻧژﻮﮐﺎﻣرﺎﻓ و ﮏﯿﺘﻨﯿﮐﻮﮐﺎﻣرﺎﻓ ،ﮏﯾژﻮﻟﻮﺗﺎﭘوﺰﯿﻓ ،یرﺎـﻤﯿﺑ ﻦـﯾا ﯽﺘﯿـﺴﻧژوﺮﺘـﻫ ﺖﯿﻫﺎـﻣ و رﺎـﻤﯿﺑ ﺮــﻫ ﻪﺑ طﻮﺑﺮﻣ گﺮــﻣ یﺎــﻘﻟا رد Fas هﺪﻧﺮﯿـــﮔ ﺖﻟﺎـﺧد زا ﯽﺗوﺎـﻔﺘﻣ ﺮـﯾﻮﺼﺗ نآ ﯽﯾﺎـﺳﺎﻨﺷ ﻪـﮐ ﺪـﻫدﯽﻣ نﺎــﺸﻧ ار ﯽﻟﻮﻠﺳ هﺪﺷ یﺰﯾرﻪﻣﺎﻧﺮﺑ .ﺖﺳا یﺮﺗﻊﯿﺳو تﺎﻌﻟﺎﻄﻣ ﺪﻨﻣزﺎﯿﻧ
ﯽﻧادرﺪﻗ و ﺮﮑﺸﺗ ﯽﮑـﺷﺰﭘ مﻮـﻠﻋ هﺎﮕـﺸﻧاد ﯽـﺸﻫوﮋﭘ ﺖﻧوﺎﻌﻣ زا ﻪﻠﯿﺳو ﻦﯾﺪﺑ رﺎﮐﺮـﺳ و سرﺪـﻣ ﺖــﯿﺑﺮﺗ هﺎﮕﺸﻧاد ،ﻪﺟدﻮﺑ ﻦﯿﻣﺎﺗ ﺖﻬﺟ ناﺮﻬﺗ ﯽﻟﻮﮑﻟﻮﻣ و ﯽﻟﻮﻠﺳ مﻮﻠﻋ تﺎﻘﯿﻘﺤﺗ ﺰﮐﺮﻣ سﺎﻨﺷرﺎﮐ تﺎﯿﺣ ﻢﻧﺎﺧ
نﺪـﺷ مﺎـﺠﻧا رد یرﺎـﮐﻢﻫ ﺖﻬــﺟ ناﺮﯾا ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد .دﻮﺷﯽﻣ ﯽﻧادرﺪﻗ و ﺮﮑﺸﺗ یﺮﺘﻣﻮﺘﯾﺎﺳﻮﻠﻓ
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Evaluation of Apoptosis Induced by Arsenic Trioxide Through Fas Pathway in Acute Promyelocytic Leukemia Patients with t(15,17)
Translocation
I II III
*A.R. Arjmand, MSc F. Zaker, Ph.D. K. Alimoghadam, MD
IV V
A. Ghavamzadeh, MD L. Moezzi, MSc
Abstract
Acute promyelocytic leukemia (APL) is a sub-type of acute myelogenous leukemia (AML) which occurs in about 10-15% of patients with AML. Approximately 20-30% of these patients, who are treated with the current standard All trans retinoic Acid(ATRA) and anthracyclines-based chemotherapy regimen, suffer relapse in less than a year. Arsenic trioxide (ATO), as a single agent, can induce complete remission even in refractory and relapsed patients with few adverse effects. Studies conducted by investigators to elucidate the mechanisms of action underlying these clinical responses have shown that Arsenic apparently affects numerous intracellular signal transduction pathways and causes many alterations in cellular function among which differentiation induction with low dose and apoptosis induction with high dose are the most prominent mechanisms. Despite previous in vitro studies, which mostly revealed that Fas/Apo 1 expression is unchanged during ATO treatment, in vivo expression of this classical receptor for apoptosis induction has not been evaluated yet. In order to study the apoptotic pattern in leukemic cells of these patients, a single-laser triple-color flowcytometric method was conducted by Annexin V and 7AAD technique, to detect leukemic apoptotic cells in a heterogeneous population of bone marrow samples. Fas/Apo 1 expression was also evaluated in promyelocyte population cells in a dual color panel. A substantial apoptosis was selectively detected in promyelocytic cells during the first and the second weeks following treatment and the concurrent Fas expression indicated its involvement in apoptosis induced by arsenic trioxide.
Key Words: 1) Acute Promyelocytic Leukemia 2) Arsenic Trioxide 3) Apoptosis 4) Fas/Apo 1 5) Flowcytometry
This article is a summary of the thesis by A.R. Arjmand for MSc degree in Hematology under supervision of F. Zaker, Ph.D. and consultation with K. Alimoghadam, MD(2003). This article was also pesented in the International Congress of Genetic of Cancer in Tehran(2003). This study was also conducted under financial support of Tehran University of Medical Sciences.(No.230/1087) I) MSc in Hematology. Hematology Oncology & BMT Research Center. Shariati Hospital, Jalale-Al-e- Ahmad Highway, Tehran University of Medical Sciences and Health Services.Tehran, Iran (*Corresponding Author)
II) Assistant Professor of Hematology. Iran University of Medical Sciences and Health Services.Tehran, Iran.
III) Assistant Professor of Hematology & Oncology. Tehran University of Medical Sciences and Health Services.Tehran, Iran.
IV) Professor of Hematology & Oncology. Tehran University of Medical Sciences and Health Services.Tehran, Iran.
V) MSc in Hematology. Tehran University of Medical Sciences and Health Services.Tehran, Iran.
