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Egzona Qipa
Muradiye Acar
Sureyya Bozkurt
Murat Buyukdogan
Hazal Berivan Sonmez
Muge Sayitoglu
Yucel Erbilgin
Zeynep Karakas
Veysel Sabri Hancer




Acute lymphoblastic leukemia (ALL) is a malignant disease of hematopoietic stem cells.
B cell ALL (B-ALL) is characterized by highly proliferative and poorly differentiated progenitor
B cells in the bone marrow. Chromosomal rearrangements, aberrant cell signaling, and mutations
lead to dysregulated cell cycle and clonal proliferation of abnormal B cell progenitors. In this study,
we aimed to examine hot spot genetic variations in the RUNX1, IDH2, and IL2RA genes in a group
of (n=52) pediatric B-ALL. Sanger sequencing results revealed a rare RUNX1 variant
p.Leu148Gln in one B-ALL patient with disease recurrence. Additionally, common intronic
variations rs12358961 and rs11256369 of IL2RA were determined in two patients. None of the
patients had the IDH2 variant.
RUNX1, IDH2, and IL2RA variations were rare events in ALL. This study detected a novel
pathogenic RUNX1 variation in a patient with a poor prognosis. Examining prognostically
important genetic anomalies of childhood lymphoblastic leukemia patients and the signaling
pathway components will pilot more accurate prognosis estimations.


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[1]. Bellavia D, Palermo R, Pia Felli M, Screpanti I, Checquolo S. Notch signaling as a therapeutic target for Acute Lymphoblastic Leukemia. Expert Opin Ther Targets Sci 2018; 12 :331-342
[2]. Cooper SL, Brown PA. Treatment of Pediatric Acute Lymphoblastic Leukemia. Pediatr Clin North Am Sci 2015; 19 : 61-73
[3]. Kruse A, Abdel-Azim N , Kim HN, Ruan Y, Phan V, Ogana H, Wang W, Lee R, Gang E, Khazal S, Kim YM. Minimal Residual Disease Detection in Acute Lymphoblastic Leukemia. Int Jou Mol Sci 2020; 6: 1054
[4]. Kamdje AHN , Krampera M. Notch signaling in acute lymphoblastic leukemia: any role for stromal microenvironment. Blood 2011; 15: 6506–6514
[5] Chung J, Riella LV, Maillard I. Targeting the Notch Pathway to Prevent Rejection. Am J Transplant 2016: 13: 3079–3085.
[6].Cooper S L, Brown P A. Treatment of Pediatric Acute Lymphoblastic Leukemia. Pediatr Clin North Am 2015:19: 61-73.
[7] Sun C, Chang L, Zhu X. Pathogenesis of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia and mechanisms underlying its relapse. Oncotarget 2017:18: 35445-35459.
[8]. Parker S, . Metallo C M. Metabolic consequences of oncogenic IDH mutations. Pharmacol Ther 2015:1: 54– 62.
[9] Triplett T, Curti B D, Bonafede P R, Miller W L, Walker E B, Weinberg A D. Defining a functionally distinct subset of human memory CD4+ T cells that are CD25POS and FOXP3. Eur. J. Immunol 2012:5: 1893–1905.
[10] Leonard W J, Donlon T A, Lebo R V, Greene W C. Localization of the Gene Encoding the Human interleukin-2 Receptor on Chromosome 10. Science.1985.28: 1547-1549.
[11] Kopan R, Ilagan MX. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell. 2009:17: 216–233.
[12] Louvi A, Artavanis-Tsakonas S. Notch and disease: A growing field. Semin Cell Dev Biol. 2012:23: 473–480. [13]. South AP, Cho RJ, Aster JC. The double-edged sword of Notch signaling in cancer. Semin Cell Dev
Biol 2012:30: 458–464.
[14]. Weng AP, Ferrando AA, Lee W, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science. 2004;8:269–271.
[15] Hamrnond D, Sather H, Nesbit M, Miller D, Coccia P, Bleyer A, Lukens J, Siegel S. Analysis of Prognostic Factors in Acute lymphoblastic Leukemia. Medical and Pediatric Oncology. 1986: 124-134.
[16] Ebens CL, Ivan M. Notch Signaling in Hematopoietic Cell Transplantation and T Cell Alloimmunity. Blood.2013:31: 271-275.
[17] Linden T, Schnittger S, Groll A H, Juergens H, Rossig C. Childhood B-cell precursor acute lymphoblastic leukaemia in a patient with familial thrombocytopenia and RUNX1 mutation. British Jou of Hematology.2010:29: 528-530.
[18] Smith BM, Arthur D , Camitta B, Carroll AJ, Crist W, Gaynon P, Gelber R, Heerema N, Korn EL, Link M, Murphy S, Pui CH, Pullen J, Reaman G, Sallan SE, Sather H, Shuster J, Simon R, Trigg M, Tubergen D, Uckun F, Ungerleider R. Uniform Approach to Risk Classification and Treatment Assignment for Children With Acute Lymphoblastic Leukemia. J Clin Oncol. 1996.14: 18-24.
[19] Mori H , Colman S M, Xiao Z, FordA M, HealyL E, Donaldson C, Hows J M, Navarrete C, Greaves M. Chromosome translocations and covert leukemic clones are generated during normal fetal development. Proc Natl Acad Sci U S A.2002:4: 8242–8247.
[20] Lie-a-ling M, Mevel R, Patel R, Blyth K, Baena E , Kouskoff V, Lacaud G. RUNX1 Dosage in Development and Cancer. Mol Cells. 2020:24: 126–138.
[21] Sood R, Kamikubo Y, Liu P. Role of RUNX1 in hematological malignancies. Blood. 2017:13: 2070–2082. [22] Yokota A, Huo L, Lan F, Wu J, Huang G. The Clinical, Molecular, and Mechanistic Basis
of RUNX1 Mutations Identified in Hematological Malignancies. Mol. Cells 2020:29:145-152.
[23] Center V, Schrappe, Aric M, Reiter A, Rizzari C, Drdelmann M, Valsecchi MG, Zimmermann M, Ludwig WD, Basso G, Masera G, Riehm H. Role of Cranial Radiotherapy for Childhood T-Cell Acute Lymphoblastic Leukemia With High WBC Count and Good Response to Prednisone. Journal of Clinical Oncology. 1997: 15: 2786-2791.
[24] Veloz IG, Martinez-Fierro ML, Jaime-Perez JC,MCarrillo-Sanchez K, Ramos-Del Hoyo MG, Lugo-Trampe A, Rojas-Martinez A, Gutierrez-Aguirre CH, Gonzalez-LlanoO, Salazar-Riojas R, Hidalgo-Miranda A, Gomez- Almaguer A, Ortiz-Lopez R. Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia.Disease Markers.2015:24:1-11.
[25] Hirabayashi S, Seki M, Hasegawa D, Kato M, Hyakuna N, Shuo T, Kimura S, Yoshida K, Kataoka K, Fujii Y, Shiraishi Y, Chiba K, Tanaka H, Kiyokawa N, Miyano S, Ogawa S, Takita J, Manabe A. Constitutional abnormalities of IDH1 combined with secondary mutations predispose a patient with Maffucci syndrome to acute lymphoblastic leukemia. Pediatr Blood Cancer.2017:24:1-4.
[26] Andersson AK, Miller DW, Lynch JA, Lemoff AS, Cai Z, Pounds SB, Radtke I, Yan B, Schuetz JD, Rubnitz JE, Ribeiro RC, Raimondi SC, Zhang J, Mullighan CG, Shurtleff SA, Schulman BA, Downing JR. IDH1 and IDH2 mutations in pediatric acute leukemia. Leukemia.2011:7:1-15.
[27] Linden T, Schnittger S, Groll AH, Juergens H, Rossig C. Childhood B-cell precursor acute lymphoblastic leukaemia in a patient with familial thrombocytopenia and RUNX1 mutation. British Journal of Haematology. 2010:29: 528-530.
[28] Varnum-Finney B., Xu, L., Brashem-Stein, C., Nourigat, C., Flowers, D., Bakkour, S., Pear, W.S., and Bernstein, I.D. 2000. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat. Med. 6: 1278-1281.