The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies

Yıl: 2019 Cilt: 36 Sayı: 2 Sayfa Aralığı: 78 - 87 Metin Dili: İngilizce İndeks Tarihi: 16-01-2020

The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies

Öz:
The introduction and advances on next-generation sequencing have led to novel ways to integrate simultaneous assessment of multiple target genes in routine laboratory analysis. Assessment of myeloid neoplasms with targeted next-generation sequencing panels shows evidence to improve diagnosis, assist therapeutic decisions, provide better information about prognosis, and better detection of minimal residual disease. Herein, we provide information for application and utilization of next-generation sequencing studies with a focus on the most important mutations in acute myeloid leukemia, myelodysplastic syndrome, myeloproliferative neoplasms, and other myelodysplastic/myeloproliferative neoplasms in order to integrate them into the daily clinical practice.
Anahtar Kelime:

Konular: Tıbbi İnformatik Tıbbi Araştırmalar Deneysel Genel ve Dahili Tıp Klinik Nöroloji Temel Sağlık Hizmetleri Sağlık Bilimleri ve Hizmetleri Cerrahi
Belge Türü: Makale Makale Türü: Derleme Erişim Türü: Erişime Açık
  • Kuo FC. Next generation sequencing in hematolymphoid neoplasia. Seminars in Hematology 2018.
  • Yohe S, Thyagarajan B. Review of Clinical Next-Generation Sequencing. Arch Pathol Lab Med 2017;141:1544-57. Sallman DA, Padron E. Integrating mutation variant allele frequency into clinical practice in myeloid malignancies. Hematol Oncol Stem Cell Ther 2016;9:89-95.
  • Jaffe E AD, Campo E, Harris NL, Quintanilla-Martinez L. Hematopathology Molecular Diagnosis in Hematopathology. Molecular Diagnosis in Hematopathology. Philadelphia PA: Elsevier; 2017:1-1216.
  • Cancer Genome Atlas Research Network, Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 2013;368:2059-74.
  • Mrozek K, Marcucci G, Paschka P, Whitman SP, Bloomfield CD. Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification? Blood 2007;109:431-48.
  • Dohner H, Weisdorf DJ, Bloomfield CD. Acute Myeloid Leukemia. N Engl J Med 2015;373:1136-52.
  • Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016;127:2391-405.
  • Duncavage EJ, Tandon B. The utility of next-generation sequencing in diagnosis and monitoring of acute myeloid leukemia and myelodysplastic syndromes. Int J Lab Hematol 2015;37(Suppl 1):115-21.
  • Sperling AS, Gibson CJ, Ebert BL. The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia. Nat Rev Cancer 2017;17:5-19.
  • Swerdlow SH CE, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J. WHO Classification of Tumours of the Haematopoietic and Lymphoid Tissues 2017.
  • Dang L, Jin S, Su SM. IDH mutations in glioma and acute myeloid leukemia. Trends Mol Med 2010;16:387-97.
  • Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 2005;352:254-66.
  • Ley TJ, Ding L, Walter MJ, McLellan MD, Lamprecht T, Larson DE, et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med 2010;363:2424-33.
  • Marcucci G, Haferlach T, Döhner H. Molecular genetics of adult acute myeloid leukemia: Prognostic and therapeutic implications. J Clin Oncol 2011;29:475-86.
  • Metzeler KH, Maharry K, Radmacher MD, Mrozek K, Margeson D, Becker H, et al. TET2 mutations improve the new European LeukemiaNet risk classification of acute myeloid leukemia: A cancer and leukemia group B study. J Clin Oncol 2011;29:1373-81.
  • Patel U, Luthra R, Medeiros LJ, Patel KP. Diagnostic, Prognostic, and Predictive Utility of Recurrent Somatic Mutations in Myeloid Neoplasms. Clin Lymphoma Myeloma Leuk 2017;17:62-74.
  • Paschka P, Schlenk RF, Gaidzik VI, Habdank M, Kronke J, Bullinger L, et al. IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication. J Clin Oncol 2010;28:3636-43.
  • Chang C-C OR. Precision Molecular Pathology of Myeloid Neoplasms. In: PT C, editor. Precision Molecular Pathology of Myeloid Neoplasms. Acute Myeloid Leukemia with Recurrent Genetic Abnormalities, Part II: Mutations Involving CEBPA, NPM1, and RUNX1: Springer International Publishing AG; 2018:427.
  • Perl AE. The role of targeted therapy in the management of patients with AML. Hematology Am Soc Hematol Educ Program 2017;2017:54-65.
  • DiNardo CD, Stein EM, de Botton S, Roboz GJ, Altman JK, Mims AS, et al. Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML. N Engl J Med 2018;378:2386-98.
  • Bains A, Luthra R, Medeiros LJ, Zuo Z. FLT3 and NPM1 mutations in myelodysplastic syndromes: Frequency and potential value for predicting progression to acute myeloid leukemia. Am J Clin Pathol 2011;135:62-9.
  • E. H. Hematopathology: A Volume in the Series: Foundations in Diagnostic Pathology. In: JR G, editor. Hematopathology. Molecular Hematopathology. 3rd ed. Philadelphia, PA: Elsevier; 2018:800.
  • Mendler JH, Maharry K, Radmacher MD, Mrozek K, Becker H, Metzeler KH, et al. RUNX1 mutations are associated with poor outcome in younger and older patients with cytogenetically normal acute myeloid leukemia and with distinct gene and MicroRNA expression signatures. J Clin Oncol 2012;30:3109-18. Gaidzik VI, Bullinger L, Schlenk RF, Zimmermann AS, Röck J, Paschka P, et al. RUNX1 mutations in acute myeloid leukemia: results from a comprehensive genetic and clinical analysis from the AML study group. J Clin Oncol 2011;29:1364-72.
  • Kussick SJ, Stirewalt DL, Yi HS, Sheets KM, Pogosova-Agadjanyan E, Braswell S, et al. A distinctive nuclear morphology in acute myeloid leukemia is strongly associated with loss of HLA-DR expression and FLT3 internal tandem duplication. Leukemia 2004;18:1591-8.
  • O’Donnell MR, Tallman MS, Abboud CN, Altman JK, Appelbaum FR, Arber DA, et al. Acute Myeloid Leukemia, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2017;15:926-57.
  • Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, et al. Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation. N Engl J Med 2017;377:454-64.
  • Assi R, Ravandi F. FLT3 inhibitors in acute myeloid leukemia: Choosing the best when the optimal does not exist. Am J Hematol 2018;93:553-63.
  • Kayser S, Levis MJ. FLT3 tyrosine kinase inhibitors in acute myeloid leukemia: clinical implications and limitations. Leuk Lymphoma 2014;55:243-55.
  • Nardi V, Hasserjian RP. Genetic Testing in Acute Myeloid Leukemia and Myelodysplastic Syndromes. Surg Pathol Clin 2016;9:143-63.
  • Kiyoi H, Naoe T. FLT3 mutations in acute myeloid leukemia. Methods Mol Med 2006;125:189-97.
  • Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med 2016;374:2209-21.
  • Patel JP, Gonen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 2012;366:1079-89.
  • Allen C, Hills RK, Lamb K, Evans C, Tinsley S, Sellar R, et al. The importance of relative mutant level for evaluating impact on outcome of KIT, FLT3 and CBL mutations in core-binding factor acute myeloid leukemia. Leukemia 2013;27:1891-901.
  • Boissel N, Leroy H, Brethon B, Philippe N, de Botton S, Auvrignon A, et al. Incidence and prognostic impact of c-Kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia (CBF-AML). Leukemia 2006;20:965-70.
  • Balsat M, Renneville A, Thomas X, de Botton S, Caillot D, Marceau A, et al. Postinduction Minimal Residual Disease Predicts Outcome and Benefit From Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia With NPM1 Mutation: A Study by the Acute Leukemia French Association Group. J Clin Oncol 2017;35:185-93.
  • Bejar R, Lord A, Stevenson K, Bar-Natan M, Pérez-Ladaga A, Zaneveld J. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood 2014;124:2705-12.
  • Medeiros BC, Fathi AT, DiNardo CD, Pollyea DA, Chan SM, Swords R. Isocitrate dehydrogenase mutations in myeloid malignancies. Leukemia 2017;31:272-81.
  • Patnaik MM, Hanson CA, Hodnefield JM, Lasho TL, Finke CM, Knudson RA, et al. Differential prognostic effect of IDH1 versus IDH2 mutations in myelodysplastic syndromes: A Mayo Clinic Study of 277 patients. Leukemia 2012;26:101-5.
  • Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med 2011;364:2496-506.
  • Gelsi-Boyer V, Brecqueville M, Devillier R, Murati A, Mozziconacci MJ, Birnbaum D. Mutations in ASXL1 are associated with poor prognosis across the spectrum of malignant myeloid diseases. J Hematol Oncol 2012;5:12.
  • Gelsi-Boyer V, Trouplin V, Adelaide J, Bonansea J, Cervera N, Carbuccia N, et al. Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. Br J Haematol 2009;145:788-800.
  • Bacher U, Haferlach T, Kern W, Haferlach C, Schnittger S. A comparative study of molecular mutations in 381 patients with myelodysplastic syndrome and in 4130 patients with acute myeloid leukemia. Haematologica 2007;92:744-52.
  • Sun QY, Ding LW, Tan KT, Chien W, Mayakonda A, Lin DC, et al. Ordering of mutations in acute myeloid leukemia with partial tandem duplication of MLL (MLL-PTD). Leukemia 2017;31:1-10.
  • Devillier R, Mansat-De Mas V, Gelsi-Boyer V, Demur C, Murati A, Corre J, et al. Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes. Oncotarget 2015;6:8388-96. Lindsley RC, Mar BG, Mazzola E, Grauman PV, Shareef S, Allen SL, et al. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood 2015;125:1367-76.
  • Rucker FG, Schlenk RF, Bullinger L, Kayser S, Teleanu V, Kett H, et al. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood 2012;119:2114-21.
  • Welch JS, Petti AA, Miller CA, Fronick CC, O’Laughlin M, Fulton RS, et al. TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes. N Engl J Med 2016;375:2023-36.
  • Welch JS, Petti AA, Ley TJ. Decitabine in TP53-Mutated AML. N Engl J Med 2017;376:797-8.
  • Jongen-Lavrencic M, Grob T, Hanekamp D, Kavelaars FG, Al Hinai A, Zeilemaker A, et al. Molecular Minimal Residual Disease in Acute Myeloid Leukemia. N Engl J Med 2018;378:1189-99.
  • Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 2017;129:424-47.
  • Li P. ORS. Acute Myeloid Leukemia with Myelodysplasia-Related Changes, Therapy-Related Myeloid Neoplasms, and Acute Myeloid Leukemia, Not Otherwise Specified. In: Chang CC, Ohgami R, editors. Precision Molecular Pathology of Myeloid Neoplasms. Springer, Cham; 2018.
  • Metzeler KH, Herold T, Rothenberg-Thurley M, Amler S, Sauerland MC, Görlich D, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood 2016;128:686-98.
  • Devillier R, Gelsi-Boyer V, Brecqueville M, Carbuccia N, Murati A, Vey N, et al. Acute myeloid leukemia with myelodysplasia-related changes are characterized by a specific molecular pattern with high frequency of ASXL1 mutations. Am J Hematol 2012;87:659-62.
  • Ohgami RS, Ma L, Merker JD, Gotlib JR, Schrijver I, Zehnder JL, et al. Next-generation sequencing of acute myeloid leukemia identifies the significance of TP53, U2AF1, ASXL1, and TET2 mutations. Mod Pathol 2015;28:706-14.
  • Bhatia S. Therapy-related myelodysplasia and acute myeloid leukemia. Semin Oncol 2013;40:666-75.
  • Ok CY, Patel KP, Garcia-Manero G, Routbort MJ, Fu B, Tang G, et al. Mutational profiling of therapy-related myelodysplastic syndromes and acute myeloid leukemia by next generation sequencing, a comparison with de novo diseases. Leuk Res 2015;39:348-54.
  • Arber DA, Slovak ML, Popplewell L, Bedell V, Ikle D, Rowley JD, et al. Therapy-related acute myeloid leukemia/myelodysplasia with balanced 21q22 translocations. Am J Clin Pathol 2002;117:306-13.
  • Czader M, Orazi A. Acute Myeloid Leukemia and Other Types of Disease Progression in Myeloproliferative Neoplasms. Am J Clin Pathol 2015;144:188-206.
  • Shih AH, Chung SS, Dolezal EK, Zhang SJ, Abdel-Wahab OI, Park CY, et al. Mutational analysis of therapy-related myelodysplastic syndromes and acute myelogenous leukemia. Haematologica 2013;98:908-12.
  • Tiu RV, Visconte V, Traina F, Schwandt A, Maciejewski JP. Updates in cytogenetics and molecular markers in MDS. Curr Hematol Malig Rep 2011;6:126-35.
  • Haase D, Germing U, Schanz J, Pfeilstöcker M, Nösslinger T, Hildebrandt B, et al. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood 2007;110:4385-95.
  • Haferlach T, Nagata Y, Grossmann V, Okuno Y, Bacher U, Nagae G, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia 2014;28:241-7.
  • Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, Van Loo P, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood 2013;122:3616-27.
  • Bartels S, Schipper E, Hasemeier B, Kreipe H, Lehmann U. Routine clinical mutation profiling using next generation sequencing and a customized gene panel improves diagnostic precision in myeloid neoplasms. Oncotarget 2016;7:30084-93.
  • Walter MJ, Ding L, Shen D, Shao J, Grillot M, McLellan M, et al. Recurrent DNMT3A mutations in patients with myelodysplastic syndromes. Leukemia 2011;25:1153-8.
  • Jadersten M, Saft L, Smith A, Kulasekararaj A, Pomplun S, Göhring G, et al. TP53 mutations in low-risk myelodysplastic syndromes with del (5q) predict disease progression. J Clin Oncol 2011;29:1971-9.
  • Kuo FC, Dong F. Next-generation sequencing-based panel testing for myeloid neoplasms. Curr Hematol Malig Rep 2015;10:104-11.
  • Papaemmanuil E, Cazzola M, Boultwood J, Malcovati L, Vyas P, Bowen D, et al. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med 2011;365:1384-95.
  • Brecqueville M, Rey J, Bertucci F, Coppin E, Finetti P, Carbuccia N, et al. Mutation analysis of ASXL1, CBL, DNMT3A, IDH1, IDH2, JAK2, MPL, NF1, SF3B1, SUZ12, and TET2 in myeloproliferative neoplasms. Genes Chromosomes Cancer 2012;51:743-55.
  • Malcovati L, Galli A, Travaglino E, Ambaglio I, Rizzo E, Molteni E, et al. Clinical significance of somatic mutation in unexplained blood cytopenia. Blood 2017;129:3371-8.
  • Jain M, Tripathi A. ICUS/CCUS/CHIP: basics & beyond. Expert Rev Hematol 2017;10:915-20.
  • Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 2014;371:2488-98.
  • Zink F, Stacey SN, Norddahl GL, Frigge ML, Magnusson OT, Jonsdottir I, et al. Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly. Blood 2017;130:742-52.
  • Brauninger A, Blau W, Kunze K, Desch AK, Brobeil A, Tur MK, et al. Targeted Next-Generation Sequencing Is a Sensitive Tool for Differential Diagnosis of Myelodysplastic Syndromes in Bone Marrow Trephines. J Mol Diagn 2018;20:344-54.
  • Barbui T, Thiele J, Gisslinger H, Kvasnicka HM, Vannucchi AM, Guglielmelli P, et al. The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion. Blood Cancer J 2018;8:15.
  • Tefferi A, Lasho TL, Schwager SM, Steensma DP, Mesa RA, Li CY, et al. The JAK2(V617F) tyrosine kinase mutation in myelofibrosis with myeloid metaplasia: lineage specificity and clinical correlates. Br J Haematol 2005;131:320-8.
  • Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005;365:1054-61.
  • Vannucchi AM, Antonioli E, Guglielmelli P, Rambaldi A, Barosi G, Marchioli R, et al. Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia. Blood 2007;110:840-6.
  • Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 2013;369:2379-90.
  • Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 2013;369:2391-405.
  • Rotunno G, Mannarelli C, Guglielmelli P, Pacilli A, Pancrazzi A, Pieri L, et al. Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood 2014;123:1552-5.
  • Tefferi A, Lasho TL, Finke C, Belachew AA, Wassie EA, Ketterling RP, et al. Type 1 vs type 2 calreticulin mutations in primary myelofibrosis: differences in phenotype and prognostic impact. Leukemia 2014;28:1568-70.
  • Mesa RA, Jamieson C, Bhatia R, Deininger MW, Fletcher CD, Gerds AT, et al. NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018. J Natl Compr Canc Netw 2017;15:1193-207.
  • Tefferi A, Guglielmelli P, Larson DR, Finke C, Wassie EA, Pieri L, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood 2014;124:2507-13.
  • Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 2006;3:270.
  • Langabeer SE, Andrikovics H, Asp J, Bellosillo B, Carillo S, Haslam K, et al. Molecular diagnostics of myeloproliferative neoplasms. Eur J Haematol 2015;95:270-9.
  • Rumi E, Pietra D, Pascutto C, Guglielmelli P, Martínez-Trillos A, Casetti I, et al. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood 2014;124:1062-9.
  • Tefferi A. Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia 2010;24:1128-38.
  • Tefferi A, Vainchenker W. Myeloproliferative neoplasms: molecular pathophysiology, essential clinical understanding, and treatment strategies. J Clin Oncol 2011;29:573-82.
  • Yogarajah M, Tefferi A. Leukemic Transformation in Myeloproliferative Neoplasms: A Literature Review on Risk, Characteristics, and Outcome. Mayo Clin Proc 2017;92:1118-28.
  • Itzykson R, Kosmider O, Renneville A, Gelsi-Boyer V, Meggendorfer M, Morabito M, et al. Prognostic score including gene mutations in chronic myelomonocytic leukemia. J Clin Oncol 2013;31:2428-36.
  • Wassie EA, Itzykson R, Lasho TL, Kosmider O, Finke CM, Hanson CA, et al. Molecular and prognostic correlates of cytogenetic abnormalities in chronic myelomonocytic leukemia: a Mayo Clinic-French Consortium Study. Am J Hematol 2014;89:1111-5.
  • Pich A, Riera L, Sismondi F, Godio L, Davico Bonino L, Marmont F, et al. JAK2V617F activating mutation is associated with the myeloproliferative type of chronic myelomonocytic leukaemia. J Clin Pathol 2009;62:798-801.
  • Padron E, Dezern A, Andrade-Campos M, Vaddi K, Scherle P, Zhang Q, et al. A Multi-Institution Phase I Trial of Ruxolitinib in Patients with Chronic Myelomonocytic Leukemia (CMML). Clin Cancer Res 2016;22:3746-54.
  • E.D. GMH. Chronic Myelomonocytic Leukemia: Clinical and Pathologic Features. In: Chung-Che (Jeff) Chang RSO, editor. Precision Molecular Pathology of Myeloid Neoplasms. VOL 12: Springer International Publishing AG 2018:2018.
  • Caye A, Strullu M, Guidez F, Cassinat B, Gazal S, Fenneteau O, et al. Juvenile myelomonocytic leukemia displays mutations in components of the RAS pathway and the PRC2 network. Nat Genet 2015;47:1334-40.
  • Niemeyer CM, Kang MW, Shin DH, Furlan I, Erlacher M, Bunin NJ, et al. Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia. Nat Genet 2010;42:794-800.
  • Gambacorti-Passerini CB, Donadoni C, Parmiani A, Pirola A, Redaelli S, Signore G, et al. Recurrent ETNK1 mutations in atypical chronic myeloid leukemia. Blood 2015;125:499-503.
  • Meggendorfer M, Bacher U, Alpermann T, Haferlach C, Kern W, Gambacorti-Passerini C, et al. SETBP1 mutations occur in 9% of MDS/MPN and in 4% of MPN cases and are strongly associated with atypical CML, monosomy 7, isochromosome i(17)(q10), ASXL1 and CBL mutations. Leukemia 2013;27:1852-60.
  • Wang SA, Tam W, Tsai AG, Arber DA, Hasserjian RP, Geyer JT, et al. Targeted next-generation sequencing identifies a subset of idiopathic hypereosinophilic syndrome with features similar to chronic eosinophilic leukemia, not otherwise specified. Mod Pathol 2016;29:854-64.
  • Arock M, Sotlar K, Akin C, Broesby-Olsen S, Hoermann G, Escribano L, et al. KIT mutation analysis in mast cell neoplasms: recommendations of the European Competence Network on Mastocytosis. Leukemia 2015;29:1223-32.
  • Schwaab J, Schnittger S, Sotlar K, Walz C, Fabarius A, Pfirrmann M, et al. Comprehensive mutational profiling in advanced systemic mastocytosis. Blood 2013;122:2460-6.
APA ÖZ PUYAN F, ALKAN S (2019). The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies. , 78 - 87.
Chicago ÖZ PUYAN FULYA,ALKAN Serhan The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies. (2019): 78 - 87.
MLA ÖZ PUYAN FULYA,ALKAN Serhan The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies. , 2019, ss.78 - 87.
AMA ÖZ PUYAN F,ALKAN S The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies. . 2019; 78 - 87.
Vancouver ÖZ PUYAN F,ALKAN S The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies. . 2019; 78 - 87.
IEEE ÖZ PUYAN F,ALKAN S "The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies." , ss.78 - 87, 2019.
ISNAD ÖZ PUYAN, FULYA - ALKAN, Serhan. "The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies". (2019), 78-87.
APA ÖZ PUYAN F, ALKAN S (2019). The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies. Balkan Medical Journal, 36(2), 78 - 87.
Chicago ÖZ PUYAN FULYA,ALKAN Serhan The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies. Balkan Medical Journal 36, no.2 (2019): 78 - 87.
MLA ÖZ PUYAN FULYA,ALKAN Serhan The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies. Balkan Medical Journal, vol.36, no.2, 2019, ss.78 - 87.
AMA ÖZ PUYAN F,ALKAN S The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies. Balkan Medical Journal. 2019; 36(2): 78 - 87.
Vancouver ÖZ PUYAN F,ALKAN S The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies. Balkan Medical Journal. 2019; 36(2): 78 - 87.
IEEE ÖZ PUYAN F,ALKAN S "The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies." Balkan Medical Journal, 36, ss.78 - 87, 2019.
ISNAD ÖZ PUYAN, FULYA - ALKAN, Serhan. "The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies". Balkan Medical Journal 36/2 (2019), 78-87.