Autopsy and Case Reports
Autopsy and Case Reports
Article / Clinical Case Report

JAK2-mutated acute myeloid leukemia: comparison of next-generation sequencing (NGS) and single nucleotide polymorphism array (SNPa) findings between two cases

Thiago Rodrigo de Noronha; Miguel Mitne-Neto; Maria de Lourdes Chauffaille

Downloads: 0
Views: 1093


JAK2 mutations are rare in de novo acute myeloid leukemia (AML), and JAK2-mutated acute myeloid leukemia (AML) patients usually have a previous history of myeloproliferative neoplasms (MPNs). Current advances in laboratory techniques, such as single nucleotide polymorphism array (SNPa) and next-generation sequencing (NGS), have facilitated new insight into the molecular basis of hematologic diseases. Herein, we present two cases of JAK2-mutated AML in which both SNPa and NGS methods added valuable information. Both cases had leukemogenic collaboration, namely, copy-neutral loss of heterozygosity (CN-LOH), detected on chromosome 9. One of the cases exhibited both JAK2 and IDH2 mutations, most likely having originated as an MPN with leukemic transformation, while the other case was classified as a de novo AML with JAK2, CEBPA, and FLT3 mutations.


Cytogenetics, Leukemia, Myeloid, Acute, Polymorphism, Single Nucleotide, Sequence Analysis, DNA


Chauffaille MLLF. Myeloproliferative neoplasms: a review of diagnostic criteria and clinical aspects. Rev Bras Hematol Hemoter. 2010;32(4):308-16. [].

Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classi fi cation of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-405. []. [PMID:27069254]

Mesa RA, Verstovsek S, Cervantes F, et al. Primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (post-PV MF), post essential thrombocythemia myelofibrosis (post-ET MF), blast phase PMF (PMF-BP): Consensus on terminology by the international working group for myelofibrosis research and treatment (IWG-MRT). Leuk Res. 2007;31(6):737-40. []. [PMID:17210175]

Mesa RA, Li CY, Ketterling RP, Schroeder GS, Knudson RA, Tefferi A. Leukemic transformation in myelofibrosis with myeloid metaplasia: A single-institution experience with 91 cases. Blood. 2005;105(3):973-7. []. [PMID:15388582]

Abdulkarim K, Girodon F, Johansson P, et al. AML transformation in 56 patients with Ph–MPD in two well defined populations. Eur J Haematol. 2009;82(2):106-11. []. [PMID:19134023]

Rampal R, Ahn J, Abdel-Wahab O, et al. Genomic and functional analysis of leukemic transformation of myeloproliferative neoplasms. Proc Natl Acad Sci USA. 2014;111(50):E5401-10. []. [PMID:25516983]

Heaney ML, Soriano G. Acute myeloid leukemia following a myeloproliferative neoplasm: Clinical characteristics, genetic features and effects of therapy. Curr Hematol Malig Rep. 2013;8(2):116-22. []. [PMID:23572311]

Lee JW, Kim YG, Soung YH, et al. The JAK2 V617F mutation in de novo acute myelogenous leukemias. Oncogene. 2006;25(9):1434-6. []. [PMID:16247455]

Hidalgo-López JE, Kanagal-Shamanna R, Medeiros LJ, et al. Morphologic and molecular characteristics of de novo AML with JAK2 V617F mutation. J Natl Compr Canc Netw. 2017;15(6):790-6. []. [PMID:28596259]

Noronha T, Mitne-Neto M, Chauffaille M. Mutational profiling of acute myeloid leukemia with normal cytogenetics in Brazilian patients: The value of next-generation sequencing for genomic classification. J Investig Med. 2017;65(8):1155-8. []. [PMID:28923882]

Pinheiro RF, Chauffaille M. Comparison of I-FISH and G-banding for the detection of chromosomal abnormalities during the evolution of myelodysplastic syndrome. Braz J Med Biol Res. 2009;42(11):42-5. []. [PMID:19855907]

Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic Classification and Prognosis in Acute Myeloid Leukemia. N Engl J Med. 2016;374(23):2209-21. []. [PMID:27276561]

Cortes JE, Kantarjian H, O’Brien S, et al. Clinical and prognostic significance of trisomy 21 in adult patients with acute myelogenous leukemia and myelodysplastic syndromes. Leukemia. 1995;9(1):115-7. [PMID:7845005]

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(4):424-47. []. [PMID:27895058]

Noronha TR, Rohr S, Chauffaille M. Identifying the similarities and differences between single nucleotide polymorphism array (SNPa) analysis and karyotyping in acute myeloid leukemia and myelodysplastic syndromes. Rev Bras Hematol Hemoter. 2015;37(1):48-54. []. [PMID:25638768]

Ley TJ, Miller C, Ding L, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059-74. []. [PMID:23634996]

Noronha T, Chauffaille M. Multiple long runs of homozygosity detected by SNP array: offspring of consanguineous parents and his siblings. Adv Cytol Pathol. 2018;3(3):56-9.

Gaymes TJ, Mohamedali A, Eiliazadeh AL, Darling D, Mufti GJ. FLT3 and JAK2 mutations in acute myeloid leukemia promote interchromosomal homologous recombination and the potential for copy neutral loss of heterozygosity. Cancer Res. 2017;77(7):1697-708. []. [PMID:28108507]

Passamonti F, Rumi E, Pietra D, et al. A prospective study of 338 patients with polycythemia vera: The impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications. Leukemia. 2010;24(9):1574-9. []. [PMID:20631743]

Lee HJ, Daver N, Kantarjian HM, Verstovsek S, Ravandi F. The role of JAK pathway dysregulation in the pathogenesis and treatment of acute myeloid leukemia. Clin Cancer Res. 2013;19(2):327-35. []. [PMID:23209034]

Im AP, Sehgal AR, Carroll MP, et al. DNMT3A and IDH mutations in acute myeloid leukemia and other myeloid malignancies: associations with prognosis and potential treatment strategies. Leukemia. 2014;28(9):1774-83. []. [PMID:24699305]

Tefferi A, Jimma T, Sulai NH, et al. IDH mutations in primary myelofibrosis predict leukemic transformation and shortened survival: clinical evidence for leukemogenic collaboration with JAK2V617F. Leukemia. 2012;26(3):475-80. []. [PMID:21912393]

Green A, Beer P. Somatic Mutations of IDH1 and IDH2 in the Leukemic Transformation of Myeloproliferative Neoplasms. N Engl J Med. 2010;362(4):369-70. []. [PMID:20107228]

McKenney AS, Lau AN, Somasundara AVH, et al. JAK2/IDH-mutant–driven myeloproliferative neoplasm is sensitive to combined targeted inhibition. J Clin Invest. 2018;128(2):789-804. []. [PMID:29355841]

Meyer SC, Levine RL. Translational implications of somatic genomics in acute myeloid leukaemia. Lancet Oncol. 2014;15(9):e382-94. []. [PMID:25079101]




Publication date:

5cbdb54e0e8825be74ac9f31 autopsy Articles
Links & Downloads

Autops Case Rep

Share this page
Page Sections