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A MOLECULAR VIEW OF RAS /RAF/MEK /ERK IN PEDIATRIC ALL

Yıl 2019, Cilt 50, Sayı 3, 162 - 166, 15.09.2019
https://doi.org/10.16948/zktipb.460772

Öz

Pediatric leukemia is thought to be a multifactorial disease that can be treated.In leukemia there are genetic changes like many other types of cancer. 
These genetic changes are effective in the activation of oncogenes or inactivation of tumor suppressor genes; can lead to the development of leukemia by causing damage to regulatory mechanisms of cell death, differentiation or division. Unspecified genetic anomalies provide the availability of treatment options that affect these steps of cell cycle. It provied that treatment
of chemotherapy-resistant and relapsing leukemia and the development of personalized treatment modalities In this review, we aimed to reveal the approach of the RAS / RAF / MEK / ERK pathway revealed in the studies that are important in the development of cancer in Acute Lymphoblastic Leukemia (ALL), a subtype of pediatric leukemia.

Kaynakça

  • 1. Golub E, Arceci RJ. Acute myelogenous leukemia. 4 ed. Philadelphia: Lippincott Williams and Wilkins Company; 2002.
  • 2. Margolin JF, Steuber CP, Poplack DG. Acute Lymphoblastic Leukemia. In: Pizzo PA, editor. Principles and Practice of Pediatric Oncology. 4 ed. Philadelphia: Lippincott Williams & Wilkins; 2002.
  • 3. Williams WJ, Beutler E, Litchman MA, Coler BS, Kipps TJ, Mauner AM. William’s Hematology. New York: McGraw Hill Company; 1991.
  • 4. Franks LM, Teich NM. Introduction to the Cellular and Molecular Biology of Cancer. New York: Oxford University Pres; 2001.
  • 5. Apak H. Çocukluk çağı lösemileri. Türk Pediatri Arşivi. 2006;41:189-96.
  • 6. Lowell C. Fundamentals of blood cell biology. In: Stites DP, Terr AI, Parslow TG, editors. Medical Immunology. 9 ed; 1997. p. 9-25.
  • 7. Oláh E. Basic Concepts of Cancer: Genomic Determination. The Journal of The International Federation of Clinical Chemistry and Laboratory Medicine 2005;16(2).
  • 8. Martinez JD, Parker MD, Fultz KE, Ignatenko NA, Gerner EW. Molecular Biology of Cancer. Arizona: John Wiley&Sons; 2003.
  • 9. Kleinsmith LJ. Principles of Cancer Biology. Michigan: Benjamin Cummings; 2006.
  • 10. Mullighan CG, Downing JR. Genome-wide profiling of genetic alterations in acute lymphoblastic leukemia: recent insights and future directions. Leukemia. 2009 Jul;23(7):1209-18.
  • 11. Durmaz ÖE. B hücre aktivasyonu ve antikor üretimi B cell activation and antibody. Türkderm. 2013;47(1):24-7.
  • 12. Look AT. Oncogenic transcription factors in the human acute leukemias. Science. 1997 Nov 7;278(5340):1059-64.
  • 13. Greaves M. Molecular genetics, natural history and the demise of childhood leukaemia. European journal of cancer. 1999 Dec;35(14):1941-53.
  • 14. Takai Y, Sasaki T, ve Matozaki T. Small GTP binding proteins. Physiol. Rev.2001; 81: 153-208.
  • 15. Hancock JF. Ras proteins: different signals from different locations. Nat. Rev. Mol. Cell. Biol. 2003; 4: 373-384.
  • 16. Knight T, Irving JA. Ras/Raf/MEK/ERK Pathway Activation in Childhood Acute Lymphoblastic Leukemia and Its Therapeutic Targeting. Front Oncol. 2014 Jun 24;4:160.
  • 17. Al-Kzayer LF, Sakashita K, Al-Jadiry MF, Al-Hadad SA, Ghali HH, Uyen le TN, Liu T, Matsuda K, Abdulkadhim JM, Al-Shujairi TA, Matti ZI, Sughayer MA, Rihani R, Madanat FF, Inoshita T, Kamata M, Koike K. Analysis of KRAS and NRAS Gene Mutations in Arab Asian Children With Acute Leukemia: High Frequency of RAS Mutations in Acute Lymphoblastic Leukemia. Pediatr Blood Cancer. 2015 Dec;62(12):2157-61.
  • 18. Perentesis JP, Bhatia S, Boyle E, Shao Y, Shu XO, Steinbuch M, Sather HN, Gaynon P, Kiffmeyer W, Envall-Fox J, Robison LL. RAS oncogene mutations and outcome of therapy for childhood acute lymphoblastic leukemia. Leukemia. 2004 Apr;18(4):685.
  • 19. Jerchel IS, Hoogkamer AQ, Ariës IM, Steeghs EMP, Boer JM, Besselink NJM,Boeree A, van de Ven C, de Groot-Kruseman HA, de Haas V, Horstmann MA, Escherich G, Zwaan CM, Cuppen E, Koudijs MJ, Pieters R, den Boer ML. RAS pathway mutations as a predictive biomarker for treatment adaptation in pediatric B-cell precursor acute lymphoblastic leukemia. Leukemia. 2018 Apr;32(4):931-940.
  • 20. Barbosa TC, Andrade FG, Lopes BA, de Andrade CF, Mansur MB, Emerenciano M, Pombo-de-Oliveira MS. Impact of mutations in FLT3, PTPN11 and RAS genes on the overall survival of pediatric B cell precursor acute lymphoblastic leukemia in Brazil. Leuk Lymphoma. 2014 Jul;55(7):1501-9.
  • 21. Lübbert M, Oster W, Knopf HP, McCormick F, Mertelsmann R, Herrmann F. N-RAS gene activation in acute myeloid leukemia: association with expression of interleukin-6. Leukemia. 1993 Dec;7(12):1948-54.
  • 22. Driessen EM, van Roon EH, Spijkers-Hagelstein JA, Schneider P, de Lorenzo P, Valsecchi MG, Pieters R, Stam RW. Frequencies and prognostic impact of RAS mutations in MLL-rearranged acute lymphoblastic leukemia in infants. Haematologica. 2013 Jun;98(6):937-44.
  • 23. Steelman LS, Franklin RA, Abrams SL, Chappell W, Kempf CR, Bäsecke J, Stivala F, Donia M, Fagone P, Nicoletti F, Libra M, Ruvolo P, Ruvolo V, Evangelisti C, Martelli AM, McCubrey JA. Roles of the Ras/Raf/MEK/ERK pathway in leukemia therapy. Leukemia. 2011 Jul;25(7):1080-94.
  • 24. Yamamoto T, Isomura M, Xu Y, Liang J, Yagasaki H, Kamachi Y, Kudo K, Kiyoi H, Naoe T,Kojma S. PTPN11, RAS and FLT3 mutations in childhood acute lymphoblastic leukemia. Leuk Res. 2006 Sep;30(9):1085-9.
  • 25. Lipka DB, Witte T, Toth R, Yang J, Wiesenfarth M, Nöllke P, Fischer A, Brocks D, Gu Z, Park J, Strahm B, Wlodarski M, Yoshimi A, Claus R, Lübbert M, Busch H,Boerries M, Hartmann M, Schönung M, Kilik U, Langstein J, Wierzbinska JA, PabstC, Garg S, Catalá A, De Moerloose B, Dworzak M, Hasle H, Locatelli F, Masetti R, Schmugge M, Smith O, Stary J, Ussowicz M, van den Heuvel-Eibrink MM, Assenov Y,Schlesner M, Niemeyer C, Flotho C, Plass C. RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia. Nat Commun. 2017 Dec19;8(1):2126.
  • 26. Case M, Matheson E, Minto L, Hassan R, Harrison CJ, Bown N, Bailey S, Vormoor J, Hall AG, Irving JA. Mutation of genes affecting the RAS pathway is common in childhood acute lymphoblastic leukemia. Cancer Res. 2008 Aug 15;68(16):6803-9.
  • 27. Jebaraj BM, Kienle D, Bühler A, Winkler D, Döhner H, Stilgenbauer S, Zenz T.BRAF mutations in chronic lymphocytic leukemia. Leuk Lymphoma. 2013 Jun;54(6):1177-82.
  • 28. Xu Y, Wertheim G, Morrissette JJ, Bagg A. BRAF kinase domain mutations in de novo acute myeloid leukemia with monocytic differentiation. Leuk Lymphoma. 2017 Mar;58(3):743-745.
  • 29. Falini B, Martelli MP, Tiacci E. BRAF V600E mutation in hairy cell leukemia: from bench to bedside. Blood. 2016 Oct 13;128(15):1918-1927.
  • 30. Alonso CM, Such E, Gómez-Seguí I, Cervera J, Martínez-Cuadrón D, Luna I, Ibáñez M, López-Pavía M, Vera B, Navarro I, Senent L, Sanz Alonso MA. BRAF V600E mutation in adult acute lymphoblastic leukemia. Leuk Lymphoma. 2013May;54(5):1105-6.
  • 31. Lee JW, Soung YH, Park WS, Kim SY, Nam SW, Min WS, Lee JY, Yoo NJ, Lee SH. BRAF mutations in acute leukemias. Leukemia. 2004 Jan;18(1):170-2.
  • 32. Gustafsson B, Angelini S, Sander B, Christensson B, Hemminki K, Kumar R. Mutations in the BRAF and N-ras genes in childhood acute lymphoblastic leukaemia. Leukemia. 2005 Feb;19(2):310-2.
  • 33. Irving J, Matheson E, Minto L, Blair H, Case M, Halsey C, Swidenbank I, Ponthan F, Kirschner-Schwabe R, Groeneveld-Krentz S, Hof J, Allan J, Harrison C, Vormoor J, von Stackelberg A, Eckert C. Ras pathway mutations are prevalent in relapsed childhood acute lymphoblastic leukemia and confer sensitivity to MEK inhibition. Blood. 2014 Nov 27;124(23):3420-30.
  • 34. Knight T, Irving JA. Ras/Raf/MEK/ERK Pathway Activation in Childhood AcuteLymphoblastic Leukemia and Its Therapeutic Targeting. Front Oncol. 2014 Jun 24;4:160.
  • 35. Estep AL, Palmer C, McCormick F, Rauen KA. Mutation analysis of BRAF, MEK1 andMEK2 in 15 ovarian cancer cell lines: implications for therapy. PLoS One. 2007Dec 5;2(12):e1279.
  • 36. Liang DC, Chen SH, Liu HC, Yang CP, Yeh TC, Jaing TH, Hung IJ, Hou JY, Lin TH,Lin CH, Shih LY. Mutational status of NRAS, KRAS, and PTPN11 genes is associated with genetic/cytogenetic features in children with B-precursor acutelymphoblastic leukemia. Pediatr Blood Cancer. 2018 Feb;65(2).
  • 37. Armstrong SA, Mabon ME, Silverman LB, Li A, Gribben JG, Fox EA, Sallan SE,Korsmeyer SJ. FLT3 mutations in childhood acute lymphoblastic leukemia. Blood.2004 May 1;103(9):3544-6.
  • 38. Akin DF, Mumcuoglu M, Aslar D, Kurekcİ AE, Ezer U, Akar N. Screening Of Flt3 Gene Mutations (flt3-ıtd-d835) In Turkish Childhood Acute Leukemıa Patients, Journal of Molecular Medicine and Clinical Applications, 2016, 2575-0305.

PEDİATRİK ALL’DE RAS/RAF/MEK/ERK YOLAĞINA MOLEKÜLER BİR BAKIŞ

Yıl 2019, Cilt 50, Sayı 3, 162 - 166, 15.09.2019
https://doi.org/10.16948/zktipb.460772

Öz

Pediatrik löseminin henüz sebebi kesin olarak bilinmeyen ancak tedavi edilebilen, multifaktöriyel bir hastalık olduğu düşünülmektedir. Lösemilerde diğer birçok kanser türü gibi genetik değişimler söz konusudur.  Onkogenlerin aktivasyonu ya da tümör baskılayıcı genlerin inaktivasyonunda etkili bu genetik lezyonlar; hücre ölümü, farklılaşma ya da bölünmenin düzenlenme mekanizmalarında hasara yol açarak lösemi gelişimine neden olabilirler. Henüz belirlenmemiş genetik anomalilerin bilinmesi bu basamaklara etki eden tedavi seçeneklerinin bulunması ve bu sayede kemoterapiye dirençli ve nüks gösteren lösemilerin tedavi edilmesine, kişiselleştirilmiş tedavi yöntemlerinin geliştirilmesine olanak sağlamaktadır. Bu derlemede kanser gelişiminde önemli olduğu yapılan çalışmalar neticesinde ortaya konulan RAS/RAF/MEK/ERK yolağının pediatrik lösemi alt türü olan Akut Lenfoblastik Lösemi’de (ALL) incelenme yaklaşımını ortaya koyabilmek amaçlanmıştır.

Kaynakça

  • 1. Golub E, Arceci RJ. Acute myelogenous leukemia. 4 ed. Philadelphia: Lippincott Williams and Wilkins Company; 2002.
  • 2. Margolin JF, Steuber CP, Poplack DG. Acute Lymphoblastic Leukemia. In: Pizzo PA, editor. Principles and Practice of Pediatric Oncology. 4 ed. Philadelphia: Lippincott Williams & Wilkins; 2002.
  • 3. Williams WJ, Beutler E, Litchman MA, Coler BS, Kipps TJ, Mauner AM. William’s Hematology. New York: McGraw Hill Company; 1991.
  • 4. Franks LM, Teich NM. Introduction to the Cellular and Molecular Biology of Cancer. New York: Oxford University Pres; 2001.
  • 5. Apak H. Çocukluk çağı lösemileri. Türk Pediatri Arşivi. 2006;41:189-96.
  • 6. Lowell C. Fundamentals of blood cell biology. In: Stites DP, Terr AI, Parslow TG, editors. Medical Immunology. 9 ed; 1997. p. 9-25.
  • 7. Oláh E. Basic Concepts of Cancer: Genomic Determination. The Journal of The International Federation of Clinical Chemistry and Laboratory Medicine 2005;16(2).
  • 8. Martinez JD, Parker MD, Fultz KE, Ignatenko NA, Gerner EW. Molecular Biology of Cancer. Arizona: John Wiley&Sons; 2003.
  • 9. Kleinsmith LJ. Principles of Cancer Biology. Michigan: Benjamin Cummings; 2006.
  • 10. Mullighan CG, Downing JR. Genome-wide profiling of genetic alterations in acute lymphoblastic leukemia: recent insights and future directions. Leukemia. 2009 Jul;23(7):1209-18.
  • 11. Durmaz ÖE. B hücre aktivasyonu ve antikor üretimi B cell activation and antibody. Türkderm. 2013;47(1):24-7.
  • 12. Look AT. Oncogenic transcription factors in the human acute leukemias. Science. 1997 Nov 7;278(5340):1059-64.
  • 13. Greaves M. Molecular genetics, natural history and the demise of childhood leukaemia. European journal of cancer. 1999 Dec;35(14):1941-53.
  • 14. Takai Y, Sasaki T, ve Matozaki T. Small GTP binding proteins. Physiol. Rev.2001; 81: 153-208.
  • 15. Hancock JF. Ras proteins: different signals from different locations. Nat. Rev. Mol. Cell. Biol. 2003; 4: 373-384.
  • 16. Knight T, Irving JA. Ras/Raf/MEK/ERK Pathway Activation in Childhood Acute Lymphoblastic Leukemia and Its Therapeutic Targeting. Front Oncol. 2014 Jun 24;4:160.
  • 17. Al-Kzayer LF, Sakashita K, Al-Jadiry MF, Al-Hadad SA, Ghali HH, Uyen le TN, Liu T, Matsuda K, Abdulkadhim JM, Al-Shujairi TA, Matti ZI, Sughayer MA, Rihani R, Madanat FF, Inoshita T, Kamata M, Koike K. Analysis of KRAS and NRAS Gene Mutations in Arab Asian Children With Acute Leukemia: High Frequency of RAS Mutations in Acute Lymphoblastic Leukemia. Pediatr Blood Cancer. 2015 Dec;62(12):2157-61.
  • 18. Perentesis JP, Bhatia S, Boyle E, Shao Y, Shu XO, Steinbuch M, Sather HN, Gaynon P, Kiffmeyer W, Envall-Fox J, Robison LL. RAS oncogene mutations and outcome of therapy for childhood acute lymphoblastic leukemia. Leukemia. 2004 Apr;18(4):685.
  • 19. Jerchel IS, Hoogkamer AQ, Ariës IM, Steeghs EMP, Boer JM, Besselink NJM,Boeree A, van de Ven C, de Groot-Kruseman HA, de Haas V, Horstmann MA, Escherich G, Zwaan CM, Cuppen E, Koudijs MJ, Pieters R, den Boer ML. RAS pathway mutations as a predictive biomarker for treatment adaptation in pediatric B-cell precursor acute lymphoblastic leukemia. Leukemia. 2018 Apr;32(4):931-940.
  • 20. Barbosa TC, Andrade FG, Lopes BA, de Andrade CF, Mansur MB, Emerenciano M, Pombo-de-Oliveira MS. Impact of mutations in FLT3, PTPN11 and RAS genes on the overall survival of pediatric B cell precursor acute lymphoblastic leukemia in Brazil. Leuk Lymphoma. 2014 Jul;55(7):1501-9.
  • 21. Lübbert M, Oster W, Knopf HP, McCormick F, Mertelsmann R, Herrmann F. N-RAS gene activation in acute myeloid leukemia: association with expression of interleukin-6. Leukemia. 1993 Dec;7(12):1948-54.
  • 22. Driessen EM, van Roon EH, Spijkers-Hagelstein JA, Schneider P, de Lorenzo P, Valsecchi MG, Pieters R, Stam RW. Frequencies and prognostic impact of RAS mutations in MLL-rearranged acute lymphoblastic leukemia in infants. Haematologica. 2013 Jun;98(6):937-44.
  • 23. Steelman LS, Franklin RA, Abrams SL, Chappell W, Kempf CR, Bäsecke J, Stivala F, Donia M, Fagone P, Nicoletti F, Libra M, Ruvolo P, Ruvolo V, Evangelisti C, Martelli AM, McCubrey JA. Roles of the Ras/Raf/MEK/ERK pathway in leukemia therapy. Leukemia. 2011 Jul;25(7):1080-94.
  • 24. Yamamoto T, Isomura M, Xu Y, Liang J, Yagasaki H, Kamachi Y, Kudo K, Kiyoi H, Naoe T,Kojma S. PTPN11, RAS and FLT3 mutations in childhood acute lymphoblastic leukemia. Leuk Res. 2006 Sep;30(9):1085-9.
  • 25. Lipka DB, Witte T, Toth R, Yang J, Wiesenfarth M, Nöllke P, Fischer A, Brocks D, Gu Z, Park J, Strahm B, Wlodarski M, Yoshimi A, Claus R, Lübbert M, Busch H,Boerries M, Hartmann M, Schönung M, Kilik U, Langstein J, Wierzbinska JA, PabstC, Garg S, Catalá A, De Moerloose B, Dworzak M, Hasle H, Locatelli F, Masetti R, Schmugge M, Smith O, Stary J, Ussowicz M, van den Heuvel-Eibrink MM, Assenov Y,Schlesner M, Niemeyer C, Flotho C, Plass C. RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia. Nat Commun. 2017 Dec19;8(1):2126.
  • 26. Case M, Matheson E, Minto L, Hassan R, Harrison CJ, Bown N, Bailey S, Vormoor J, Hall AG, Irving JA. Mutation of genes affecting the RAS pathway is common in childhood acute lymphoblastic leukemia. Cancer Res. 2008 Aug 15;68(16):6803-9.
  • 27. Jebaraj BM, Kienle D, Bühler A, Winkler D, Döhner H, Stilgenbauer S, Zenz T.BRAF mutations in chronic lymphocytic leukemia. Leuk Lymphoma. 2013 Jun;54(6):1177-82.
  • 28. Xu Y, Wertheim G, Morrissette JJ, Bagg A. BRAF kinase domain mutations in de novo acute myeloid leukemia with monocytic differentiation. Leuk Lymphoma. 2017 Mar;58(3):743-745.
  • 29. Falini B, Martelli MP, Tiacci E. BRAF V600E mutation in hairy cell leukemia: from bench to bedside. Blood. 2016 Oct 13;128(15):1918-1927.
  • 30. Alonso CM, Such E, Gómez-Seguí I, Cervera J, Martínez-Cuadrón D, Luna I, Ibáñez M, López-Pavía M, Vera B, Navarro I, Senent L, Sanz Alonso MA. BRAF V600E mutation in adult acute lymphoblastic leukemia. Leuk Lymphoma. 2013May;54(5):1105-6.
  • 31. Lee JW, Soung YH, Park WS, Kim SY, Nam SW, Min WS, Lee JY, Yoo NJ, Lee SH. BRAF mutations in acute leukemias. Leukemia. 2004 Jan;18(1):170-2.
  • 32. Gustafsson B, Angelini S, Sander B, Christensson B, Hemminki K, Kumar R. Mutations in the BRAF and N-ras genes in childhood acute lymphoblastic leukaemia. Leukemia. 2005 Feb;19(2):310-2.
  • 33. Irving J, Matheson E, Minto L, Blair H, Case M, Halsey C, Swidenbank I, Ponthan F, Kirschner-Schwabe R, Groeneveld-Krentz S, Hof J, Allan J, Harrison C, Vormoor J, von Stackelberg A, Eckert C. Ras pathway mutations are prevalent in relapsed childhood acute lymphoblastic leukemia and confer sensitivity to MEK inhibition. Blood. 2014 Nov 27;124(23):3420-30.
  • 34. Knight T, Irving JA. Ras/Raf/MEK/ERK Pathway Activation in Childhood AcuteLymphoblastic Leukemia and Its Therapeutic Targeting. Front Oncol. 2014 Jun 24;4:160.
  • 35. Estep AL, Palmer C, McCormick F, Rauen KA. Mutation analysis of BRAF, MEK1 andMEK2 in 15 ovarian cancer cell lines: implications for therapy. PLoS One. 2007Dec 5;2(12):e1279.
  • 36. Liang DC, Chen SH, Liu HC, Yang CP, Yeh TC, Jaing TH, Hung IJ, Hou JY, Lin TH,Lin CH, Shih LY. Mutational status of NRAS, KRAS, and PTPN11 genes is associated with genetic/cytogenetic features in children with B-precursor acutelymphoblastic leukemia. Pediatr Blood Cancer. 2018 Feb;65(2).
  • 37. Armstrong SA, Mabon ME, Silverman LB, Li A, Gribben JG, Fox EA, Sallan SE,Korsmeyer SJ. FLT3 mutations in childhood acute lymphoblastic leukemia. Blood.2004 May 1;103(9):3544-6.
  • 38. Akin DF, Mumcuoglu M, Aslar D, Kurekcİ AE, Ezer U, Akar N. Screening Of Flt3 Gene Mutations (flt3-ıtd-d835) In Turkish Childhood Acute Leukemıa Patients, Journal of Molecular Medicine and Clinical Applications, 2016, 2575-0305.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Bilimleri ve Hizmetleri
Bölüm Orjinal Araştırma
Yazarlar

Dilara Fatma AKIN (Sorumlu Yazar)
TIP FAKÜLTESİ
Türkiye


Burcu BİTERGE SÜT
TIP FAKÜLTESİ
Türkiye

Yayımlanma Tarihi 15 Eylül 2019
Yayınlandığı Sayı Yıl 2019, Cilt 50, Sayı 3

Kaynak Göster

Bibtex @derleme { zktipb460772, journal = {Zeynep Kamil Tıp Bülteni}, issn = {1300-7971}, eissn = {2148-4864}, address = {}, publisher = {Zeynep Kamil Kadın ve Çocuk Hastalıkları EAH}, year = {2019}, volume = {50}, pages = {162 - 166}, doi = {10.16948/zktipb.460772}, title = {PEDİATRİK ALL’DE RAS/RAF/MEK/ERK YOLAĞINA MOLEKÜLER BİR BAKIŞ}, key = {cite}, author = {Akın, Dilara Fatma and Biterge Süt, Burcu} }
APA Akın, D. F. & Biterge Süt, B. (2019). PEDİATRİK ALL’DE RAS/RAF/MEK/ERK YOLAĞINA MOLEKÜLER BİR BAKIŞ . Zeynep Kamil Tıp Bülteni , 50 (3) , 162-166 . DOI: 10.16948/zktipb.460772
MLA Akın, D. F. , Biterge Süt, B. "PEDİATRİK ALL’DE RAS/RAF/MEK/ERK YOLAĞINA MOLEKÜLER BİR BAKIŞ" . Zeynep Kamil Tıp Bülteni 50 (2019 ): 162-166 <https://dergipark.org.tr/tr/pub/zktipb/issue/47961/460772>
Chicago Akın, D. F. , Biterge Süt, B. "PEDİATRİK ALL’DE RAS/RAF/MEK/ERK YOLAĞINA MOLEKÜLER BİR BAKIŞ". Zeynep Kamil Tıp Bülteni 50 (2019 ): 162-166
RIS TY - JOUR T1 - PEDİATRİK ALL’DE RAS/RAF/MEK/ERK YOLAĞINA MOLEKÜLER BİR BAKIŞ AU - Dilara Fatma Akın , Burcu Biterge Süt Y1 - 2019 PY - 2019 N1 - doi: 10.16948/zktipb.460772 DO - 10.16948/zktipb.460772 T2 - Zeynep Kamil Tıp Bülteni JF - Journal JO - JOR SP - 162 EP - 166 VL - 50 IS - 3 SN - 1300-7971-2148-4864 M3 - doi: 10.16948/zktipb.460772 UR - https://doi.org/10.16948/zktipb.460772 Y2 - 2019 ER -
EndNote %0 Zeynep Kamil Tıp Bülteni PEDİATRİK ALL’DE RAS/RAF/MEK/ERK YOLAĞINA MOLEKÜLER BİR BAKIŞ %A Dilara Fatma Akın , Burcu Biterge Süt %T PEDİATRİK ALL’DE RAS/RAF/MEK/ERK YOLAĞINA MOLEKÜLER BİR BAKIŞ %D 2019 %J Zeynep Kamil Tıp Bülteni %P 1300-7971-2148-4864 %V 50 %N 3 %R doi: 10.16948/zktipb.460772 %U 10.16948/zktipb.460772
ISNAD Akın, Dilara Fatma , Biterge Süt, Burcu . "PEDİATRİK ALL’DE RAS/RAF/MEK/ERK YOLAĞINA MOLEKÜLER BİR BAKIŞ". Zeynep Kamil Tıp Bülteni 50 / 3 (Eylül 2019): 162-166 . https://doi.org/10.16948/zktipb.460772
AMA Akın D. F. , Biterge Süt B. PEDİATRİK ALL’DE RAS/RAF/MEK/ERK YOLAĞINA MOLEKÜLER BİR BAKIŞ. Zeynep Kamil Tıp Bülteni. 2019; 50(3): 162-166.
Vancouver Akın D. F. , Biterge Süt B. PEDİATRİK ALL’DE RAS/RAF/MEK/ERK YOLAĞINA MOLEKÜLER BİR BAKIŞ. Zeynep Kamil Tıp Bülteni. 2019; 50(3): 162-166.
IEEE D. F. Akın ve B. Biterge Süt , "PEDİATRİK ALL’DE RAS/RAF/MEK/ERK YOLAĞINA MOLEKÜLER BİR BAKIŞ", Zeynep Kamil Tıp Bülteni, c. 50, sayı. 3, ss. 162-166, Eyl. 2019, doi:10.16948/zktipb.460772