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Atoofa Rukhsar
Muhammad Tayyab
Asma Ahmed
Sara Zahid
Hafsa Ashfaq
Sarwat Naeem
Mehrunissa Akbar Ali
Neha Iqbal Sargana
Laiba Malik
Areesha Malik
Rehana Badar


Acute myeloid leukemia (AML), AML1-ETO, CBFB-MYH11, NRAS, NPM1, SNPs


Acute myeloid leukemia (AML) is one of the first tumor types sequenced at the whole genome level, in which mutations in nucleophosmin NPM1 and RAS are the most frequently acquired molecular abnormalities. In a current study, human blood samples of AML patients were collected from Jinnah hospital, Mayo hospital and Institute of Nuclear Medicine and Oncology (INMOL), Lahore. Clinical and haematological characteristic of AML patients of different age groups and genders according to AML1-ETO and CBFB-MYH11 transcripts, followed by the analysis of Neuroblastoma RAS (NRAS) coding sequence mutation, Nucleophosmin1 (NPM1) gene coding sequence mutation and NPM1 3’UTR Variant mutation through DNA and RNA isolation, Primer designing and sequence analysis through RT-PCR, which led to the detection of frequencies of FAB sub-types and frequency distribution of N-RAS and NPM1 gene mutations in AML Pakistani patients. Statistically analysed results indicated that prevalence of this disease is common in adults (85.71%) as compared to paediatric (14.28%). AML fusion oncogene (AML1-ETO) was detected in 26.6% AML patients, with higher frequency in AML-M2 patients (34.2%). The percentage of AML patients with error was 2.86% with the frequency of 0.02. SNP5 and was not deviated from SNP1 and SNP2 because it also showed similar results, except for gender based (both) data (p >0.001) and it shows significant correlation of gender with SNP5 while all other parameters gave non-significant results (p< 0.001). However, mutation in NRAS gene was detected in total 51.4% of AML patients. In conclusion, the role of different types of NPM1 mutations, either individually or in the presence of RAS mutations may be essential for AML prognosis.

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1. Abelson S, Collord G, Ng SWK, et al. Prediction of acute myeloid leukaemia risk in healthy individuals. Nature 2018; 559:400-4.
2. Altman JK, Foran JM, Pratz KW, et al. Phase 1 study of quizartinib in combination with induction and consolidation chemotherapy in patients with newly diagnosed acute myeloid leukemia. Am J Hematol 2018;93:213-21.
3. Byrd JC, Mrozek K, Dodge RK, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood. 2002;100:4325-4336.
4. Daver N, Cortes J, Ravandi F, et al. Secondary mutations as mediators of resistance to targeted therapy in leukemia. Blood 2015;125:3236-45.
5. Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 2017;129:424-47.
6. Grimwade D, Walker H, Harrison G, et al. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood. 2001;98:1312-1320.
7. Grimwade D, Walker H, Oliver F, et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children’s Leukaemia Working Parties. Blood. 1998;92:2322-2333.
8. Gunawardane RN, Nepomuceno RR, Rooks AM, et al. Transient exposure to quizartinib mediates sustained inhibition of FLT3 signaling while specifically inducing apoptosis in FLT3-activated leukemia cells. Mol Cancer Ther 2013;12:438-47.
9. Kottaridis PD, Gale RE, Frew ME, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood 2001;98:1752-9.
10. Liu Y, Cheng Z, Li Q, et al. Prognostic significance of the PANK family expression in acute myeloid leukemia. Ann Transl Med 2019;7:261.
11. Lowenberg B, Downing JR, Burnett A. Acute myeloid leukemia. N Engl J Med. 1999;341:1051- 1062.
12. Mannelli F, Ponziani V, Bencini S, et al. CEBPA-doublemutated acute myeloid leukemia displays a unique phenotypic profile: a reliable screening method and insight into biological features. Haematologica 2017;102:529-40.
13. Patnaik MM. The importance of FLT3 mutational analysis in acute myeloid leukemia. Leukemia & lymphoma 2018;59:2273-86.
14. Port M, Böttcher M, Thol F, et al. Prognostic significance of FLT3 internal tandem duplication, nucleophosmin 1, and CEBPA gene mutations for acute myeloid leukemia patients with normal karyotype and younger than 60 years: a systematic review and meta-analysis. Ann Hematol 2014;93:1279-86.
15. Pronier E, Bowman RL, Ahn J, et al. Genetic and epigenetic evolution as a contributor to WT1-mutant leukemogenesis. Blood 2018;132:1265-78.
16. Slovak ML, Kopecky KJ, Cassileth PA, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood. 2000;96:4075-4083.
17. Stein EM, DiNardo CD, Pollyea DA, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood 2017;130:722-31.
18. Welch JS. Patterns of mutations in TP53 mutated AML. Best Pract Res Clin Haematol 2018;31:379-83.
19. Zhu Z, Bai Y, Lu X, Ding J, Qi C. Rapamycin downregulates NKG2D ligands in acute myeloid leukemia cells via an activation of the STAT3 pathway: a potential mechanism for rapamycin-induced immune escape in leukemia. Transl Cancer Res 2019;8:473-82.