c-Myc Inhibition Induces an Additive Effect with Cyclophosphamide in Acute Lymphoblastic Leukemia
Background: Cellular-myelocytomatosis (c-Myc), an oncoprotein and a transcription factor, is involved in several essential cellular processes. The c-Myc expression level is highly regulated in normal cells. It has been proved that c-Myc expression is deregulated in malignant cells due to rearrangeme...
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| Language: | English |
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Tabriz University of Medical Sciences
2024-08-01
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| Series: | ImmunoAnalysis |
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| Online Access: | https://ia.tbzmed.ac.ir/PDF/ia-4-6.pdf |
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| author | Mohammad Sadeghi Maryam Panahi Zahra Kheyrizadeh Leili Aghebati-Maleki Ali Akbar Movasaghpour Akbari Abbas Ali Hosseinpour Feizi Sima Shahmohammadi Farid Sanam Dolati Farhad Jadidi-Niaragh |
| author_facet | Mohammad Sadeghi Maryam Panahi Zahra Kheyrizadeh Leili Aghebati-Maleki Ali Akbar Movasaghpour Akbari Abbas Ali Hosseinpour Feizi Sima Shahmohammadi Farid Sanam Dolati Farhad Jadidi-Niaragh |
| author_sort | Mohammad Sadeghi |
| collection | DOAJ |
| description | Background: Cellular-myelocytomatosis (c-Myc), an oncoprotein and a transcription factor, is involved in several essential cellular processes. The c-Myc expression level is highly regulated in normal cells. It has been proved that c-Myc expression is deregulated in malignant cells due to rearrangements and mutations. The overexpression of this molecule is also reported to be present in acute lymphoblastic leukemia (ALL) as well, which is correlated with an unfavorable response to treatment, poor prognosis, and decreased overall survival. The upregulation of c-Myc results in increased proliferation, cell growth, and survival of ALL cells. Hence, making it an ideal target for leukemia treatment. This study evaluates the effect of c-Myc silencing combined with cyclophosphamide treatment, an FDA-approved chemotherapeutic. Methods: Peripheral blood and bone marrow samples (mononuclear cells) were derived from eleven ALL patients. To silence c-Myc, small interfering-RNA (siRNA)-lipofectamine was used. The efficacy of gene silencing was assessed by the qRT-PCR test. Next, the effect of c-Myc silencing combined with cyclophosphamide treatment in ALL primary cells was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) test. Results: ALL cells were successfully transfected with c-Myc-siRNA. Also, treating cells with cyclophosphamide exerted a slight fall in the c-Myc mRNA level. The MTT test revealed that following the inhibition of c-Myc by siRNA, the viability of primary ALL cells decreased in response to cyclophosphamide treatment. Also, it was discovered that silencing c-Myc with siRNA combined with cyclophosphamide treatment significantly inhibits the growth of primary ALL cells compared to cyclophosphamide monotherapy. Conclusion: c-Myc possesses high potential in the treatment of several cancers. Our findings add ALL to this category as well. Silencing c-Myc sensitizes ALL cells to cyclophosphamide treatment and can help with the better treatment of the afflicted individuals. |
| format | Article |
| id | doaj-art-e612a22f7ee8409a9aeb33e184b936de |
| institution | DOAJ |
| issn | 2783-2589 |
| language | English |
| publishDate | 2024-08-01 |
| publisher | Tabriz University of Medical Sciences |
| record_format | Article |
| series | ImmunoAnalysis |
| spelling | doaj-art-e612a22f7ee8409a9aeb33e184b936de2025-08-20T03:06:57ZengTabriz University of Medical SciencesImmunoAnalysis2783-25892024-08-01416610.34172/ia.4086ia-4086c-Myc Inhibition Induces an Additive Effect with Cyclophosphamide in Acute Lymphoblastic LeukemiaMohammad Sadeghi0Maryam Panahi1Zahra Kheyrizadeh2Leili Aghebati-Maleki3Ali Akbar Movasaghpour Akbari4Abbas Ali Hosseinpour Feizi5Sima Shahmohammadi Farid6Sanam Dolati7Farhad Jadidi-Niaragh8Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, IranImmunology Research Center, Tabriz University of Medical Sciences, Tabriz, IranStudent Research Committee, Tabriz University of Medical Sciences, Tabriz, IranImmunology Research Center, Tabriz University of Medical Sciences, Tabriz, IranHematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, IranHematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, IranHematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, IranHematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, IranImmunology Research Center, Tabriz University of Medical Sciences, Tabriz, IranBackground: Cellular-myelocytomatosis (c-Myc), an oncoprotein and a transcription factor, is involved in several essential cellular processes. The c-Myc expression level is highly regulated in normal cells. It has been proved that c-Myc expression is deregulated in malignant cells due to rearrangements and mutations. The overexpression of this molecule is also reported to be present in acute lymphoblastic leukemia (ALL) as well, which is correlated with an unfavorable response to treatment, poor prognosis, and decreased overall survival. The upregulation of c-Myc results in increased proliferation, cell growth, and survival of ALL cells. Hence, making it an ideal target for leukemia treatment. This study evaluates the effect of c-Myc silencing combined with cyclophosphamide treatment, an FDA-approved chemotherapeutic. Methods: Peripheral blood and bone marrow samples (mononuclear cells) were derived from eleven ALL patients. To silence c-Myc, small interfering-RNA (siRNA)-lipofectamine was used. The efficacy of gene silencing was assessed by the qRT-PCR test. Next, the effect of c-Myc silencing combined with cyclophosphamide treatment in ALL primary cells was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) test. Results: ALL cells were successfully transfected with c-Myc-siRNA. Also, treating cells with cyclophosphamide exerted a slight fall in the c-Myc mRNA level. The MTT test revealed that following the inhibition of c-Myc by siRNA, the viability of primary ALL cells decreased in response to cyclophosphamide treatment. Also, it was discovered that silencing c-Myc with siRNA combined with cyclophosphamide treatment significantly inhibits the growth of primary ALL cells compared to cyclophosphamide monotherapy. Conclusion: c-Myc possesses high potential in the treatment of several cancers. Our findings add ALL to this category as well. Silencing c-Myc sensitizes ALL cells to cyclophosphamide treatment and can help with the better treatment of the afflicted individuals.https://ia.tbzmed.ac.ir/PDF/ia-4-6.pdfc-myccyclophosphamideacute lymphoblastic leukemiasirna |
| spellingShingle | Mohammad Sadeghi Maryam Panahi Zahra Kheyrizadeh Leili Aghebati-Maleki Ali Akbar Movasaghpour Akbari Abbas Ali Hosseinpour Feizi Sima Shahmohammadi Farid Sanam Dolati Farhad Jadidi-Niaragh c-Myc Inhibition Induces an Additive Effect with Cyclophosphamide in Acute Lymphoblastic Leukemia ImmunoAnalysis c-myc cyclophosphamide acute lymphoblastic leukemia sirna |
| title | c-Myc Inhibition Induces an Additive Effect with Cyclophosphamide in Acute Lymphoblastic Leukemia |
| title_full | c-Myc Inhibition Induces an Additive Effect with Cyclophosphamide in Acute Lymphoblastic Leukemia |
| title_fullStr | c-Myc Inhibition Induces an Additive Effect with Cyclophosphamide in Acute Lymphoblastic Leukemia |
| title_full_unstemmed | c-Myc Inhibition Induces an Additive Effect with Cyclophosphamide in Acute Lymphoblastic Leukemia |
| title_short | c-Myc Inhibition Induces an Additive Effect with Cyclophosphamide in Acute Lymphoblastic Leukemia |
| title_sort | c myc inhibition induces an additive effect with cyclophosphamide in acute lymphoblastic leukemia |
| topic | c-myc cyclophosphamide acute lymphoblastic leukemia sirna |
| url | https://ia.tbzmed.ac.ir/PDF/ia-4-6.pdf |
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