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3 results on '"Shereen A. Turkistany"'

1. ETV6-RUNX1 interacts with a region in SPIB intron 1 to regulate gene expression in pre-B-cell acute lymphoblastic leukemia

Author

Li S. Xu, Devanshi Shukla, Rodney P. DeKoter, Carolina R. Batista, Alison Wong, Alyssa Francis, and Shereen A. Turkistany

Subjects
Cyclin-Dependent Kinase Inhibitor p21, 0301 basic medicine, Cancer Research, Oncogene Proteins, Fusion, Chromosomes, Human, Pair 21, CARD11, Apoptosis, Biology, Response Elements, medicine.disease_cause, Translocation, Genetic, Fusion gene, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell Line, Tumor, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, hemic and lymphatic diseases, Gene expression, Genetics, medicine, Humans, Molecular Biology, Cell Proliferation, Regulation of gene expression, Mutation, Chromosomes, Human, Pair 12, Gene Expression Regulation, Leukemic, Intron, Cell Biology, Hematology, Introns, Cell biology, CARD Signaling Adaptor Proteins, DNA-Binding Proteins, 030104 developmental biology, RUNX1, chemistry, Guanylate Cyclase, 030220 oncology & carcinogenesis, Core Binding Factor Alpha 2 Subunit, Chromatin immunoprecipitation, Transcription Factors
Abstract

The most frequently occurring genetic abnormality in pediatric B-lymphocyte-lineage acute lymphoblastic leukemia is the t(12;21) chromosomal translocation that results in a ETV6-RUNX1 (also known as TEL-AML1) fusion gene. Expression of ETV6-RUNX1 induces a preleukemic condition leading to acquisition of secondary driver mutations, but the mechanism is poorly understood. SPI-B (encoded by SPIB) is an important transcriptional activator of B-cell development and differentiation. We hypothesized that SPIB is directly transcriptionally repressed by ETV6-RUNX1. Using chromatin immunoprecipitation, we identified a regulatory region in the first intron of SPIB that interacts with ETV6-RUNX1. Mutation of the RUNX1 binding site in SPIB intron 1 prevented transcriptional repression in transient transfection assays. Next, we sought to determine to what extent gene expression in REH cells can be altered by ectopic SPI-B expression. SPI-B expression was forced using CRISPR-mediated gene activation and also using a retroviral vector. Forced expression of SPI-B resulted in altered gene expression and, at high levels, impaired cell proliferation and induced apoptosis. Finally, we identified CARD11 and CDKN1A (encoding p21) as transcriptional targets of SPI-B involved in regulation of proliferation and apoptosis. Taken together, this study identifies SPIB as an important target of ETV6-RUNX1 in regulation of B-cell gene expression in t(12;21) leukemia.

Published
2019

2. Abstracts from the 3rd International Genomic Medicine Conference (3rd IGMC 2015)

Author

Jerry W. Shay, Noriko Homma, Ruyun Zhou, Muhammad Imran Naseer, Adeel G. Chaudhary, Mohammed Al-Qahtani, Nobutaka Hirokawa, Maryam Goudarzi, Albert J. Fornace, Saleh Baeesa, Deema Hussain, Mohammed Bangash, Fahad Alghamdi, Hans-Juergen Schulten, Angel Carracedo, Ishaq Khan, Hanadi Qashqari, Nawal Madkhali, Mohamad Saka, Kulvinder S. Saini, Awatif Jamal, Jaudah Al-Maghrabi, Adel Abuzenadah, Adeel Chaudhary, Mohammed Al Qahtani, Ghazi Damanhouri, Heba Alkhatabi, Anne Goodeve, Laura Crookes, Nikolas Niksic, Nicholas Beauchamp, Adel M. Abuzenadah, Jim Vaught, Bruce Budowle, Mourad Assidi, Abdelbaset Buhmeida, Leena Merdad, Sudhir Kumar, Sayaka Miura, Karen Gomez, Mahmood Rasool, Ahmed Rebai, Sajjad Karim, Hend F. Nour Eldin, Heba Abusamra, Elham M. Alhathli, Nada Salem, Mohammed H. Al-Qahtani, Hossam Faheem, Ashok Agarwa, Eberhard Nieschlag, Joachim Wistuba, Oliver S. Damm, Mohd A. Beg, Taha A. Abdel-Meguid, Hisham A. Mosli, Osama S. Bajouh, Serdar Coskun, Muhammad Abu-Elmagd, Ashraf Dallol, Sahar Hakamy, Wejdan Al-Qahtani, Asia Al-Harbi, Shireen Hussain, Burak Ozkosem, Rick DuBois, Safia S. Messaoudi, Maryam T. Dandana, Touhami Mahjoub, Wassim Y. Almawi, S. Abdalla, M. Nabil Al-Aama, Asmaa Elzawahry, Tsuyoshi Takahashi, Sachiyo Mimaki, Eisaku Furukawa, Rie Nakatsuka, Isao Kurosaka, Takahiko Nishigaki, Hiromi Nakamura, Satoshi Serada, Tetsuji Naka, Seiichi Hirota, Tatsuhiro Shibata, Katsuya Tsuchihara, Toshirou Nishida, Mamoru Kato, Sajid Mehmood, Naeem Mahmood Ashraf, Awais Asif, Muhammad Bilal, Malik Siddique Mehmood, Aadil Hussain, Qazi Mohammad Sajid Jamal, Mughees Uddin Siddiqui, Mohammad A. Alzohairy, Mohammad A. Al Karaawi, Taoufik Nedjadi, Heba Al-Khattabi, Adel Al-Ammari, Ahmed Al-Sayyad, Hédia Zitouni, Nozha Raguema, Marwa Ben Ali, Wided Malah, Raja Lfalah, Wassim Almawi, Mohammed Elanbari, Andrey Ptitsyn, Sana Mahjoub, Rabeb El Ghali, Bechir Achour, Nidhal Ben Amor, Brahim N’siri, Hamid Morjani, Esam Azhar, Vera Chayeb, Maryam Dendena, Hedia Zitouni, Khedija Zouari-Limayem, Bassem Refaat, Ahmed M. Ashshi, Sarah A. Batwa, Hazem Ramadan, Amal Awad, Ahmed Ateya, Adel Galal Ahmed El-Shemi, Ahmad Ashshi, Mohammed Basalamah, Youjin Na, Chae-Ok Yun, Adel Galal El-Shemi, Osama Kensara, Amr Abdelfattah, Batol Imran Dheeb, Mohammed M. F. Al-Halbosiy, Rghad Kadhim Al lihabi, Basim Mohammed Khashman, Djouhri Laiche, Chaudhary Adeel, Nedjadi Taoufik, Hani Al-Afghani, Maria Łastowska, Haya H. Al-Balool, Harsh Sheth, Emma Mercer, Jonathan M. Coxhead, Chris P. F. Redfern, Heiko Peters, Alastair D. Burt, Mauro Santibanez-Koref, Chris M. Bacon, Louis Chesler, Alistair G. Rust, David J. Adams, Daniel Williamson, Steven C. Clifford, Michael S. Jackson, Mala Singh, Mohmmad Shoab Mansuri, Shahnawaz D. Jadeja, Hima Patel, Yogesh S. Marfatia, Rasheedunnisa Begum, Amal M. Mohamed, Alaa K. Kamel, Nivin A. Helmy, Sayda A. Hammad, Hesham F. Kayed, Marwa I. Shehab, Assad El Gerzawy, Maha M. Ead, Ola M. Ead, Mona Mekkawy, Innas Mazen, Mona El-Ruby, S. M. A. Shahid, J. M. Arif, Mohtashim Lohani, Moumni Imen, Chaouch Leila, Ouragini Houyem, Douzi Kais, Chaouachi Dorra Mellouli Fethi, Bejaoui Mohamed, Abbes Salem, Areeg Faggad, Amanuel T. Gebreslasie, Hani Y. Zaki, Badreldin E. Abdalla, Maha S. AlShammari, Rhaya Al-Ali, Nader Al-Balawi, Mansour Al-Enazi, Ali Al-Muraikhi, Fadi Busaleh, Ali Al-Sahwan, Francis Borgio, Abdulazeez Sayyed, Amein Al-Ali, Sadananda Acharya, Maha S. Zaki, Hala T. El-Bassyouni, Mohammed F. Elshal, Kaleemuddin M., Alia M. Aldahlawi, Omar Saadah, J. Philip McCoy, Adel E. El-Tarras, Nabil S. Awad, Abdulla A. Alharthi, Mohamed M. M. Ibrahim, Haneen S. Alsehli, Abdullah M. Gari, Mohammed M. Abbas, Roaa A. Kadam, Mazen M. Gari, Mohmmed H. Alkaff, Mamdooh A. Gari, Hend F. Nour eldin, Fatima A. Moradi, Omran M. Rashidi, Zuhier A. Awan, Ibrahim Hamza Kaya, Olfat Al-Harazi, Dilek Colak, Nabila A. Alkousi, Takis Athanasopoulos, Afnan O. Bahmaid, Etimad A. Alhwait, Mohammed H. Alkaf, Roaa Kadam, Gauthaman Kalamegam, Elham Alhathli, Salma N. Alsayed, Fawziah H. Aljohani, Samaher M. Habeeb, Rawan A. Almashali, Sulman Basit, Samia M. Ahmed, Rakesh Sharma, Ashok Agarwal, Damayanthi Durairajanayagam, Luna Samanta, Edmund S. Sabanegh, Zhihong Cui, Alaa A. Alboogmi, Nuha A. Alansari, Maha M. Al-Quaiti, Fai T. Ashgan, Afnan Bandah, Hasan S. Jamal, Abdullraheem Rozi, Zeenat Mirza, Ahmad J. Al Sayyad, Hasan M. A. Farsi, Jaudah A. Al-Maghrabi, Reem Alotibi, Alaa Al-Ahmadi, Alaa A. Albogmi, Rasha A. Ebiya, Samia M. Darwish, Metwally M. Montaser, Vladimir B. Bajic, Wafaey Gomaa, Mehenaz Hanbazazh, Mahmoud Al-Ahwal, Saher Hakamy, Ghali Baba, Abdullah Al-Harbi, Ghalia Baba, Hend Nour Eldin, Aisha A. Alyamani, Rawan Gadi, Saadiah M. Alfakeeh, Rubi Ghazala, Shilu Mathew, M. Haroon Hamed, Ishtiaq Qadri, Lobna Mira, Manal Shaabad, Mikhlid H. Almutairi, Angie Ambers, Jennifer Churchill, Jonathan King, Monika Stoljarova, Harrell Gill-King, Muhammad Al-Qatani, Farid Ahmed, Taha Abo Almagd, Muhammad Al-Qahtani, Abdelbaset Buhmaida, Rukhsana Satar, Waseem Ahmad, Nazia Nazam, Mohamad I. Lone, Muhammad I. Naseer, Mohammad S. Jamal, Syed K. Zaidi, Peter N. Pushparaj, Mohammad A. Jafri, Shakeel A. Ansari, Mohammed H. Alqahtani, Hanan Bashier, Abrar Al Qahtani, Amal M. Nour, Adel M. Abu Zenadah, Muhammed Al Qahtani, Muhammad Faheem, Shiny Mathew, Peter Natesan Pushparaj, Mohammad H. Al-Qahtani, Hani A. Alhadrami, Ibtessam R. Hussein, Rima S. Bader, Randa Bassiouni, Maha Alquaiti, Fai Ashgan, Hans Schulten, Mohamed Nabil Alama, Mohammad H. Al Qahtani, Mohammad I. Lone, Nazia Nizam, Muhammed H. Al-Qahtani, Eradah Alshihri, Lina Alharbi, Peter Pushparaj Natesan, Fazal Khan, Khalid Hussain Wali Sait, Nisreen Anfinan, Lobna S. Mira, Mohammed H. AlQahtani, Sameera Sogaty, Randa I. Bassiouni, Abdulrahman M. S. Sibiani, Mohiuddin K. Warsi, null Rubi, Kundan Kumar, Ahmad A. T. Naqvi, Faizan Ahmad, Md I. Hassan, Ashraf Ali, Jummanah Jarullah, Abdelbasit Buhmeida, Shahida Khan, Ghufrana Abdussami, Maryam Mahfooz, Mohammad A. Kamal, Ghazi A. Damanhouri, Bushra Jarullah, Mohammad S. S. Jarullah, Osama Bajouh, Abdulah E. A. Mathkoor, Hashim M. A. Alsalmi, Anas M. M. Oun, Ghazi A. Damanhauri, Adeel G. Chudhary, Yousif A. Abutalib, Daniele Merico, Susan Walker, Christian R. Marshall, Mehdi Zarrei, Stephen W. Scherer, Fai Talal Ashgan, Syed Kashif Zaidi, Mohammed M. Jan, Maryam Al-Zahrani, Sahira Lary, Emmanuel Dermitzakis, Abeer A. Al-refai, Mona Saleh, Rehab I. Yassien, Mahmmoud Kamel, Rabab M. Habeb, Najlaa Filimban, Nadia Ghannam, Adel Mohammed Abuzenadah, Fehmida Bibi, Sana Akhtar, Esam I. Azhar, Muhammad Yasir, Muhammad I. Nasser, Asif A. Jiman-Fatani, Ali Sawan, Ruaa A. Lahzah, Asho Ali, Syed A. Hassan, Seyed E. Hasnain, Iftikhar A. Tayubi, Hamza A. Abujabal, Alaa O. Magrabi, Adel Abuzenada, Taha Abduallah Kumosani, Elie Barbour, Manal Shabaad, Adnan Merdad, Kalamegam Gauthaman, Mamdooh Gari, Hani M. A. Aljahdali, Reham Al Nono, Haneen Alsehli, Mohammed Abbas, Mohammed Sarwar Jamal, Shakeel Ansari, Mansour A. Alghamdi, Magdy Shamy, Max Costa, Mamdouh I. Khoder, Najla Kharrat, Sabrine Belmabrouk, Rania Abdelhedi, Riadh Benmarzoug, Mohammed H. Al Qahtani, Ghazi Dhamanhouri, Abdelwahab Noorwali, Mohammad Khalid Alwasiyah, Afnan Bahamaid, Saadiah Alfakeeh, Aisha Alyamani, Ali Mobasheri, Mohammad Sarwar Jamal, Raziuddin Khan, Kanchan Bhatia, Saif Ahmad, Iftikhar AslamTayubi, Manish Tripathi, Syed Asif Hassan, Rahul Shrivastava, Syed Hassan, Hamza A. S. Abujabal, Ishani Shah, Ishfaq A. Sheikh, Ejaz Ahmad, Mohd Rehan, Samera F. AlBasri, Rola F. Turki, Sahar A. F. Hammoudah, Khalid M. AlHarbi, Lama M. El-Attar, Ahmed M. Z. Darwish, Sara M. Ibrahim, Hani Choudhry, Jalaludden Awlia, Imran khan, Sameera Al-basri, Taha Kumosani, Heba M. EL Sayed, Eman A. Hafez, Aisha Hassan Elaimi, Randa Ibrahim Bassiouni, Richard F. Wintle, Vikram Gopalakrishna Pillai, Sujata Sharma, Punit Kaur, Alagiri Srinivasan, Tej P. Singh, Fatima Al-Adwani, Deema Hussein, Mona Al-Sharif, Fahad Al-Ghamdi, Saleh S. Baeesa, Taha Abdullah Kumosani, Faisal A. Al-Allaf, Zainularifeen Abduljaleel, Abdullah Alashwal, Mohiuddin M. Taher, Abdellatif Bouazzaoui, Halah Abalkhail, Faisal A. Ba-Hammam, Mohammad Athar, Khalid HussainWali Sait, Naira Ben Mami, Yosr Z. Haffani, Mouna Medhioub, Lamine Hamzaoui, Ameur Cherif, Msadok Azouz, Mohammed Imran Nasser, Shereen A. Turkistany, Lina M. Al-harbi, Jamal Sabir, Basmah Al-Madoudi, Bayan Al-Aslani, Khulud Al-Harbi, Rwan Al-Jahdali, Hanadi Qudaih, Emad Al Hamzy, Asad M. Ilyas, Youssri Ahmed, Mohammed Alqahtani, Alaa Alamandi, Ohoud Subhi, Nadia Bagatian, Adel Al-Johari, Osman Abdel Al-Hamour, Hosam Al-Aradati, Abdulmonem Al-Mutawa, Faisal Al-Mashat, Mohammad Al-Qahtani, Muhammad W. shah, Esam I Azhar, Saad Al-Masoodi, Emna Khamla, Chaima Jlassi, Ahmed S. Masmoudi, Lassaad Belbahri, Shadi Al-Khayyat, Roba Attas, Atlal Abu-Sanad, Mohammed Abuzinadah, Habib Bouazzi, Carlos Trujillo, Maha Alotaibi, Rami Nassir, Essam H. Jiffri, Ghulam M. Ashraf, Mohammad A. Aziz, Rizwan Ali, Nusaibah Samman, Sathish Periyasamy, Mohammed Aldress, Majed Al Otaibi, Zeyad Al Yousef, Mohamed Boudjelal, Ibrahim AlAbdulkarim, Mohd Suhail, Abid Qureshi, Adil Jamal, Mahmoud Z. El-Readi, Safaa Y. Eid, Michael Wink, Ahmed M. Isa, Lulu Alnuaim, Johara Almutawa, Basim Abu-Rafae, Saleh Alasiri, Saleh Binsaleh, and Mohamed H. Alqahtani

Subjects
0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, Differentially expressed genes, Gene expression, Genetics, Feature selection, Computational biology, Biology, Cluster analysis, Classifier (UML), Biotechnology
Published
2016

3. PU.1 opposes IL-7-dependent proliferation of developing B cells with involvement of the direct target gene bruton tyrosine kinase

Author

Ian Welch, Li S. Xu, Rodney P. DeKoter, Lauren A. Solomon, Edmund Yim, Gillian I. Bell, Darah Christie, David A. Hess, Stephen K. H. Li, and Shereen A. Turkistany

Subjects
medicine.medical_treatment, Immunology, Antigens, CD19, Gene Expression, Apoptosis, Mice, immune system diseases, hemic and lymphatic diseases, Proto-Oncogene Proteins, medicine, Agammaglobulinaemia Tyrosine Kinase, Immunology and Allergy, Bruton's tyrosine kinase, Animals, B cell, STAT5, Cell Proliferation, Mice, Knockout, B-Lymphocytes, biology, Cell growth, Interleukin-7, Protein-Tyrosine Kinases, medicine.anatomical_structure, Cytokine, Cell culture, Cancer research, biology.protein, Trans-Activators, Ectopic expression, Bone marrow, Gene Deletion
Abstract

Deletion of genes encoding the E26 transformation-specific transcription factors PU.1 and Spi-B in B cells (CD19-CreΔPB mice) leads to impaired B cell development, followed by B cell acute lymphoblastic leukemia at 100% incidence and with a median survival of 21 wk. However, little is known about the target genes that explain leukemogenesis in these mice. In this study we found that immature B cells were altered in frequency in the bone marrow of preleukemic CD19-CreΔPB mice. Enriched pro–B cells from CD19-CreΔPB mice induced disease upon transplantation, suggesting that these were leukemia-initiating cells. Bone marrow cells from preleukemic CD19-CreΔPB mice had increased responsiveness to IL-7 and could proliferate indefinitely in response to this cytokine. Bruton tyrosine kinase (BTK), a negative regulator of IL-7 signaling, was reduced in preleukemic and leukemic CD19-CreΔPB cells compared with controls. Induction of PU.1 expression in cultured CD19-CreΔPB pro–B cell lines induced Btk expression, followed by reduced STAT5 phosphorylation and early apoptosis. PU.1 and Spi-B regulated Btk directly as shown by chromatin immunoprecipitation analysis. Ectopic expression of BTK was sufficient to induce apoptosis in cultured pro–B cells. In summary, these results suggest that PU.1 and Spi-B activate Btk to oppose IL-7 responsiveness in developing B cells.

Published
2014

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