43
edits
Changes
→Recurrent Genomic Alterations in AML Detected by Chromosomal Microarray (Literature Review)
Table 1. A comprehensive list of copy number alterations detectable by CMA testing with strong diagnostic, prognostic and treatment implications in AML. Clinical significance and level of evidence are defined as described in the methods.
==Recurrent Genomic Alterations in AML Detected by Chromosomal Microarray (Literature Review)==
Table 1 - A comprehensive list of CNAs and CN-LOH detectable by CMA testing with strong diagnostic, prognostic and treatment implications in AML. Table derived from Xu et al., 2018 [PMID 30344013] with permission from Cancer Genetics.
{| class="wikitable"
{| class="wikitable"
|-
|-
! Chromosome
!Chromosome
! AML Subtype
!AML Subtype
! Abnormality Type (Gain, Loss, CN-LOH)
!Abnormality Type (Amplification, Loss, CN-LOH)
! Region
!Region
! Relevant Genes (if known)
!Relevant Genes (if known)
! Clinical Significance
!Clinical Significance
! Level of Evidence
!Level of Evidence
! Reference
!References
|-
|-
| 1
|1
| AML including NK-AML
|AML including NK-AML
| CN-LOH
|CN-LOH
| 1p
|1p
|
|
| D
|D
| 3
|3
| [11, 29, 30, 67-69, 102-104]
|<ref name=":0">Gronseth CM, McElhone SE, Storer BE, Kroeger KA, Sandhu V, Fero ML, Appelbaum FR, Estey EH, Fang M. Prognostic significance of acquired copy-neutral loss of heterozygosity in acute myeloid leukemia. Cancer 2015;121:2900–8, PMID 26033747</ref><ref name=":1">Yi JH, Huh J, Kim HJ, Kim SH, Kim HJ, Kim YK, Sohn SK, MoonJH, Kim SH, Kim KH, Won JH, Mun YC, Kim H, Park J, Jung CW, Kim DH. Adverse prognostic impact of abnormal lesions detected by genome-wide single nucleotide polymorphism array-based karyotyping analysis in acute myeloid leukemia with normal karyotype. J Clin Oncol Offic J Am Soc Clin Oncol, 29 (2011), pp. 4702-4708, [https://www.ncbi.nlm.nih.gov/pubmed/?term=Adverse+prognostic+impact+of+abnormal+lesions+detected+by+genome-wide+single+nucleotide+polymorphism+array-based+karyotyping+analysis+in+acute+myeloid+leukemia+with+normal+karyotype PMID 2208437]</ref><ref name=":2">L Bullinger, J Kronke, C Schon, I Radtke, K Urlbauer, UBotzenhardt, V Gaidzik, A Cario, C Senger, RF Schlenk, JRDowning, K Holzmann, K Dohner, H Dohner. Identification of acquired copy number alterations and uniparental disomies in cytogenetically normal acute myeloid leukemia using high-resolution single-nucleotide polymorphism analysis. Leukemia, 24 (2010), pp. 438-449, [https://www.ncbi.nlm.nih.gov/pubmed/?term=Identification+of+acquired+copy+number+alterations+and+uniparental+disomies+in+cytogenetically+normal+acute+myeloid+leukemia+using+high-resolution+single-nucleotide+polymorphism+analysis PMID 20016533]</ref><ref name=":3">AJ Dunbar, LP Gondek, CL O'Keefe, H Makishima, MS Rataul, HSzpurka, MA Sekeres, Wang XF, MA McDevitt, JP Maciejewski 250K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies. Cancer Res, 68 (2008), pp. 10349-10357, [https://www.ncbi.nlm.nih.gov/pubmed/?term=250K+single+nucleotide+polymorphism+array+karyotyping+identifies+acquired+uniparental+disomy+and+homozygous+mutations%2C+including+novel+missense+substitutions+of+c-Cbl%2C+in+myeloid+malignancies PMID 19074904]</ref><ref name=":12">Kronke J, Bullinger L, Teleanu V, Tschurtz F, Gaidzik VI, Kuhn MW, Rucker FG, Holzmann K, Paschka P, Kapp-Schworer S, Spath D, Kindler T, Schittenhelm M, Krauter J, Ganser A, Gohring G, Schlegelberger B, Schlenk RF, Dohner H, Dohner K. Clonal evolution in relapsed NPM1-mutated acute myeloid leukemia. Blood 2013;122:100–8, [https://www.ncbi.nlm.nih.gov/pubmed/?term=Clonal+evolution+in+relapsed+NPM1-mutated+acute+myeloid+leukemia. PMID 23704090]</ref><ref name=":13">M Koren-Michowitz, A Sato-Otsubo, A Nagler, T Haferlach, S Ogawa, HP Koeffler. Older patients with normal karyotype acute myeloid leukemia have a higher rate of genomic changes compared to young patients as determined by SNP array analysis. Leukem Res, 36 (2012), pp. 467-473, [https://www.ncbi.nlm.nih.gov/pubmed/22071139 PMID 22071139]</ref><ref name=":4">L Bullinger, S Frohling. Array-based cytogenetic approaches in acute myeloid leukemia: clinical impact and biological insights. Sem Oncol, 39 (2012), pp. 37-46, [https://www.ncbi.nlm.nih.gov/pubmed/22289490 PMID 22289490]</ref><ref name=":20">Barresi V, Romano A, Musso N, Capizzi C, Consoli C, Martelli MP, Palumbo G, DiRaimondo F, Condorelli DF. Broad copy neutral loss of heterozygosity regions and rare recurring copy number abnormalities in normal karyotype acute myeloid leukemia genomes. Genes Chromos Cancer 2010;49:1014–23., [https://www.ncbi.nlm.nih.gov/pubmed/20725993 PMID 20725993]</ref><ref name=":5">T Akagi, S Ogawa, M Dugas, N Kawamata, G Yamamoto, YNannya, M Sanada, CW Miller, Yung A, S Schnittger, T Haferlach, C Haferlach, HP Koeffler. Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotype. Haematologica, 94 (2009), pp. 213-223, [https://www.ncbi.nlm.nih.gov/pubmed/19144660 PMID 19144660]</ref>
|-
|-
| 2
|2
| AML
|AML
| CN-LOH
|CN-LOH
| 2p
|2p
| ''DNMT3A''
|''[[DNMT3A]]''
| D
|D
| 3
|3
| [11, 65, 100]
|<ref name=":0" /><ref name=":6">M Gupta, M Raghavan, RE Gale, C Chelala, C Allen, G Molloy, TChaplin, DC Linch, JB Cazier, Young BD. Novel regions of acquired uniparental disomy discovered in acute myeloid leukemia. Genes Chromos Cancer, 47 (2008), pp. 729-739, [https://www.ncbi.nlm.nih.gov/pubmed/18506749 PMID 18506749]</ref><ref>T McKerrell, T Moreno, H Ponstingl, N Bolli, JM Dias, G Tischler, V Colonna, B Manasse, A Bench, D Bloxham, B Herman, DFletcher, N Park, MA Quail, N Manes, C Hodkinson, J Baxter, JSierra, T Foukaneli, AJ Warren, Chi J, P Costeas, R Rad, B Huntly, C Grove, Ning Z, C Tyler-Smith, I Varela, M Scott, J Nomdedeu, VMustonen, GS Vassiliou. Development and validation of a comprehensive genomic diagnostic tool for myeloid malignancies. Blood, 128 (2016), pp. e1-e9, [https://www.ncbi.nlm.nih.gov/pubmed/27121471 PMID 27121471]</ref>
|-
|-
| 3
|3
| NK-AML, sAML
|NK-AML, sAML
| Loss
|Loss
| 3p14.1
|3p14.1
| ''FOXP1''
|''[[FOXP1]]''
| D
|D
| 3
|3
| [30, 57, 66]
|<ref name=":2" /><ref name=":7">N Itzhar, P Dessen, S Toujani, N Auger, C Preudhomme, CRichon, V Lazar, V Saada, A Bennaceur, JH Bourhis, S de Botton, ABernheim. Chromosomal minimal critical regions in therapy-related leukemia appear different from those of de novo leukemia by high-resolution aCGH. PloS One, 6 (2011), p. e16623, [https://www.ncbi.nlm.nih.gov/pubmed/21339820 PMID 21339820]</ref><ref name=":8">JD Milosevic, A Puda, L Malcovati, T Berg, M Hofbauer, AStukalov, T Klampfl, AS Harutyunyan, H Gisslinger, B Gisslinger, TBurjanivova, E Rumi, D Pietra, C Elena, AM Vannucchi, MDoubek, D Dvorakova, B Robesova, R Wieser, E Koller, NSuvajdzic, D Tomin, N Tosic, J Colinge, Z Racil, M Steurer, SPavlovic, M Cazzola, R Kralovics. Clinical significance of genetic aberrations in secondary acute myeloid leukemia. Am J Hematol, 87 (2012), pp. 1010-1016, [https://www.ncbi.nlm.nih.gov/pubmed/22887079 PMID 22887079]</ref>
|-
|-
| 4
|4
| sAML, pAML
|sAML, pAML
| CN-LOH
|CN-LOH
| 4q24
|4q24
| ''TET2''
|''[[TET2]]''
| D
|D
| 3
|3
| [67, 71, 105]
|<ref name=":3" /><ref>B Parkin, H Erba, P Ouillette, D Roulston, A Purkayastha, J Karp, M Talpaz, L Kujawski, S Shakhan, Li C, K Shedden, SN Malek. Acquired genomic copy number aberrations and survival in adult acute myelogenous leukemia. Blood, 116 (2010), pp. 4958-4967, [https://www.ncbi.nlm.nih.gov/pubmed/20729466 PMID 20729466]</ref><ref name=":21">J Flach, F Dicker, S Schnittger, S Schindela, A Kohlmann, THaferlach, W Kern, C Haferlach. An accumulation of cytogenetic and molecular genetic events characterizes the progression from MDS to secondary AML: an analysis of 38 paired samples analyzed by cytogenetics, molecular mutation analysis and SNP microarray profiling. Leukemia, 25 (2011), pp. 713-718, [https://www.ncbi.nlm.nih.gov/pubmed/21233836 PMID 21233836]</ref>
|-
|-
| 4
|4
| AML, NK-AML, sAML
|AML, NK-AML, sAML
| Loss
|Loss
| 4q24
|4q24
| ''TET2''
|''[[TET2]]''
| D, P
|D, P
| 3
|3
| [42, 45, 66]
|<ref name=":8" /><ref>S Weissmann, T Alpermann, V Grossmann, A Kowarsch, NNadarajah, C Eder, F Dicker, A Fasan, C Haferlach, T Haferlach, WKern, S Schnittger, A Kohlmann. Landscape of TET2 mutations in acute myeloid leukemia. Leukemia, 26 (2012), pp. 934-942, [https://www.ncbi.nlm.nih.gov/pubmed/22116554 PMID 22116554]</ref><ref name=":9">U Bacher, S Weissmann, A Kohlmann, S Schindela, T Alpermann, S Schnittger, W Kern, T Haferlach, C Haferlach. TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele. Br J Haematol, 156 (2012), pp. 67-75, [https://www.ncbi.nlm.nih.gov/pubmed/22017486 PMID 22017486]</ref>
|-
|-
| 5
|5
| pAML, sAML
|pAML, sAML
| Loss
|Loss
| 5q
|5q
|
|
| D
|D
| 1
|1
| [24, 33, 45, 49, 57, 66, 77, 87, 88, 106-108]
|<ref name=":7" /><ref name=":8" /><ref name=":9" /><ref name=":10">R Bajaj, Xu F, Xiang B, K Wilcox, AJ Diadamo, R Kumar, APietraszkiewicz, S Halene, Li P. Evidence-based genomic diagnosis characterized chromosomal and cryptic imbalances in 30 elderly patients with myelodysplastic syndrome and acute myeloid leukemia. Mol Cytogenet, 4 (2011), p. 3, [https://www.ncbi.nlm.nih.gov/pubmed/21251322 PMID 21251322]</ref><ref name=":14">B Parkin, P Ouillette, M Yildiz, K Saiya-Cork, K Shedden, SN Malek. Integrated genomic profiling, therapy response, and survival in adult acute myelogenous leukemia. Clin Cancer Res Offic J Am Assocr Cancer Res, 21 (2015), pp. 2045-2056, [https://www.ncbi.nlm.nih.gov/pubmed/25652455 PMID 25652455]</ref><ref name=":11">MJ Walter, JE Payton, RE Ries, WD Shannon, H Deshmukh, ZhaoY, J Baty, S Heath, P Westervelt, MA Watson, MH Tomasson, RNagarajan, BP O'Gara, CD Bloomfield, K Mrozek, RR Selzer, TARichmond, J Kitzman, J Geoghegan, PS Eis, R Maupin, RS Fulton, M McLellan, RK Wilson, ER Mardis, DC Link, TA Graubert, JFDiPersio, TJ Ley. Acquired copy number alterations in adult acute myeloid leukemia genomes. Proc Natl Acad Sci USA, 106 (2009), pp. 12950-12955, [https://www.ncbi.nlm.nih.gov/pubmed/19651600 PMID 19651600]</ref><ref name=":15">FG Rucker, RF Schlenk, L Bullinger, S Kayser, V Teleanu, H Kett, MHabdank, CM Kugler, K Holzmann, VI Gaidzik, P Paschka, GHeld, M von Lilienfeld-Toal, M Lubbert, S Frohling, T Zenz, JKrauter, B Schlegelberger, A Ganser, P Lichter, K Dohner, HDohner. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood, 119 (2012), pp. 2114-2121, [https://www.ncbi.nlm.nih.gov/pubmed/22186996 PMID 22186996]</ref><ref>A Jerez, LP Gondek, AM Jankowska, H Makishima, B Przychodzen, Tiu RV, CL O'Keefe, AM Mohamedali, D Batista, MA Sekeres, MAMcDevitt, GJ Mufti, JP Maciejewski. Topography, clinical, and genomic correlates of 5q myeloid malignancies revisited. J Clin Oncol Offic J Am Soc Clin Oncol, 30 (2012), pp. 1343-1349, [https://www.ncbi.nlm.nih.gov/pubmed/22370328 PMID 22370328]</ref><ref name=":22">M Mehrotra, R Luthra, F Ravandi, RL Sargent, BA Barkoh, RAbraham, BM Mishra, LJ Medeiros, KP Patel. Identification of clinically important chromosomal aberrations in acute myeloid leukemia by array-based comparative genomic hybridization. Leukemia Lymph, 55 (2014), pp. 2538-2548, [https://www.ncbi.nlm.nih.gov/pubmed/24446873 PMID 24446873]</ref><ref name=":23">Kim MH, J Stewart, C Devlin, Kim YT, E Boyd, M Connor. The application of comparative genomic hybridization as an additional tool in the chromosome analysis of acute myeloid leukemia and myelodysplastic syndromes. Cancer Genet Cytogen, 126 (2001), pp. 26-33, [https://www.ncbi.nlm.nih.gov/pubmed/11343775 PMID 11343775]</ref><ref name=":24">Rumi E, Harutyunyan A, Elena C, Pietra D, Klampfl T, Bagien-ski K, Berg T, Casetti I, Pascutto C, Passamonti F, Kralovics R, Cazzola M. Identification of genomic aberrations associated with disease transformation by means of high resolution SNP array analysis in patients with myeloproliferative neoplasm. Am J Hematol 2011;86:974–9, [https://www.ncbi.nlm.nih.gov/pubmed/21953568 PMID 21953568]</ref><ref name=":16">LP Gondek, Tiu R, CL O'Keefe, MA Sekeres, KS Theil, JPMaciejewski. Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML. Blood, 111 (2008), pp. 1534-1542, [https://www.ncbi.nlm.nih.gov/pubmed/17954704 PMID 17954704]</ref>
|-
|-
| 6
|6
| AML including NK-AML
|AML including NK-AML
| CN-LOH
|CN-LOH
| 6p
|6p
|
|
| D
|D
| 3
|3
| [29, 30, 102, 104]
|<ref name=":1" /><ref name=":2" /><ref name=":4" /><ref name=":5" />
|-
|-
| 7
|7
| AML including NK-AML
|AML including NK-AML
| CN-LOH
|CN-LOH
| 7q
|7q
| ''EZH2''
|''[[EZH2]]''
| D
|D
| 3
|3
| [67, 102, 109]
|<ref name=":3" /><ref name=":4" /><ref name=":17">A Tyybakinoja, E Elonen, H Vauhkonen, J Saarela, S Knuutila. Single nucleotide polymorphism microarray analysis of karyotypically normal acute myeloid leukemia reveals frequent copy number neutral loss of heterozygosity. Haematologica, 93 (2008), pp. 631-632, [https://www.ncbi.nlm.nih.gov/pubmed/18379011 PMID 18379011]</ref>
|-
|-
| 7
|7
| NK-AML, pAML, sAML
|NK-AML, pAML, sAML
| Loss
|Loss
| 7q
|7q
| ''EZH2, CUX1''
|''[[EZH2]], [[CUX1]]''
| D
|D
| 1
|1
| [28, 57, 66, 110]
|<ref name=":7" /><ref name=":8" /><ref name=":18">Huh J, Jung CW, Kim HJ, Kim YK, Moon JH, Sohn SK, Kim HJ, Min WS, Kim DH. Different characteristics identified by single nucleotide polymorphism array analysis in leukemia suggest the need for different application strategies depending on disease category. Genes Chromos cancer, 52 (2013), pp. 44-55, [https://www.ncbi.nlm.nih.gov/pubmed/23023762 PMID 23023762]</ref><ref>ME McNerney, CD Brown, X Wang, ET Bartom, S Karmakar, CBandlamudi, Yu S, Ko J, BP Sandall, T Stricker, J Anastasi, RLGrossman, JM Cunningham, MM Le Beau, KP White. CUX1 is a haploinsufficient tumor suppressor gene on chromosome 7 frequently inactivated in acute myeloid leukemia. Blood, 121 (2013), pp. 975-983, [https://www.ncbi.nlm.nih.gov/pubmed/23212519 PMID 23212519]</ref>
|-
|-
| 8
|8
| complex karyotype AML
|AML with complex karyotype
| Amplification
|Amplification
| 8q24
|8q24
| ''MYC''
|''[[MYC]]''
| D, P
|D, P
| 3
|3
| [24, 49, 61]
|<ref name=":10" /><ref name=":11" /><ref name=":25">FG Rucker, L Bullinger, C Schwaenen, DB Lipka, S Wessendorf, SFrohling, M Bentz, S Miller, C Scholl, RF Schlenk, B Radlwimmer, HA Kestler, JR Pollack, P Lichter, K Dohner, H Dohner. Disclosure of candidate genes in acute myeloid leukemia with complex karyotypes using microarray-based molecular characterization. J Clin Oncol Offic J Am Soc Clin Oncol, 24 (2006), pp. 3887-3894, [https://www.ncbi.nlm.nih.gov/pubmed/16864856 PMID 16864856]</ref>
|-
|-
| 9
|9
| NK-AML, sAML
|NK-AML, sAML
| CN-LOH
|CN-LOH
| 9p
|9p
| ''JAK2''
|''[[JAK2]]''
| D
|D
| 3
|3
| [66, 67, 104]
|<ref name=":3" /><ref name=":5" /><ref name=":8" />
|-
|-
| 11*
|11*
| AML w complex karyotype
|AML with complex karyotype
| Amplification
|Amplification
| 11q23
|11q23
| ''MLL (KMT2A)''
|''[[KMT2A|MLL (KMT2A)]]''
| D, P
|D, P
| 3
|3
| [49, 111]
|<ref name=":11" /><ref name=":19">E Kjeldsen. Oligo-based high-resolution aCGH analysis enhances routine cytogenetic diagnostics in haematological malignancies. Cancer Genom Proteom, 12 (2015), pp. 301-337, [https://www.ncbi.nlm.nih.gov/pubmed/26543079 PMID 26543079]</ref>
|-
|-
| 11*
|11*
| AML
|AML
| CN-LOH
|CN-LOH
| 11p
|11p
| ''WT1''
|''[[WT1]]''
| D
|D
| 3
|3
| [11, 30, 65, 102]
|<ref name=":0" /><ref name=":2" /><ref name=":4" /><ref name=":6" />
|-
|-
| 11
|11
| pAML, sAML, NK-AML
|pAML, sAML, NK-AML
| CN-LOH
|CN-LOH
| 11q
|11q
| ''CBL''
|''[[CBL]]''
| D
|D
| 3
|3
| [11, 65-67, 102]
|<ref name=":0" /><ref name=":3" /><ref name=":4" /><ref name=":6" /><ref name=":8" />
|-
|-
| 12
|12
| AML, NK-AML, AML w complex karyotype, sAML
|AML, NK-AML, AML with complex karyotype, sAML
| Loss
|Loss
| 12p13.2
|12p13.2
| ''ETV6''
|''[[ETV6]]''
| D
|D
| 3
|3
| [24, 30, 33, 49, 57, 61, 66, 77, 104, 108, 111-115]
|<ref name=":2" /><ref name=":5" /><ref name=":7" /><ref name=":8" /><ref name=":10" /><ref name=":14" /><ref name=":11" /><ref name=":15" /><ref name=":16" /><ref name=":19" /><ref>Paulsson K, Heidenblad M, Strombeck B, Staaf J, Jonsson G, Borg A, Fioretos T, Johansson B. High-resolution genome-wide array-based comparative genome hybridization reveals cryptic chromosome changes in AML and MDS cases with trisomy 8 as the sole cytogenetic aberration. Leukemia 2006;20:840–6. [https://www.ncbi.nlm.nih.gov/pubmed/16498392 PMID 16498392]</ref><ref>Feurstein S, Rucker FG, Bullinger L, Hofmann W, Manuk-jan G, Gohring G, Lehmann U, Heuser M, Ganser A, Dohner K, Schlegelberger B, Steinemann D. Haploinsufficiency of ETV6 and CDKN1B in patients with acute myeloid leukemia and complex karyotype. BMC Genom 2014;15:784. [https://www.ncbi.nlm.nih.gov/pubmed/25213837 PMID 25213837]</ref><ref name=":26">Zhang R, Kim YM, Wang X, Li Y, Lu X, Sternenberger AR, Li S, Lee JY. Genomic copy number variations in the myelodysplastic syndrome and acute myeloid leukemia patients with del(5q) and/or -7/del(7q). Int J Med Sci 2015;12:719–26, [https://www.ncbi.nlm.nih.gov/pubmed/26392809 PMID 26392809]</ref><ref>Wall M, Rayeroux KC, MacKinnon RN, Zordan A, Campbell LJ. ETV6 deletion is a common additional abnormality in patients with myelodysplastic syndromes or acute myeloid leukemia and monosomy 7. Haematologica 2012;97:1933–6., [https://www.ncbi.nlm.nih.gov/pubmed/22875624 PMID 22875624]</ref>
|-
|-
| 13*
|13*
| pAML, NK-AML, NPM1 mutated AML, FLT3-ITD pos AML, sAML
|pAML, NK-AML, ''NPM1'' mutated AML, FLT3-ITD positive AML, sAML
| CN-LOH
|CN-LOH
| 13q
|13q
| ''FLT3''
|''[[FLT3]]''
| D, P
|D, P
| 2
|2
| [11, 28-31, 65-69, 102, 104, 109, 116-118]
|<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3" /><ref name=":12" /><ref name=":13" /><ref name=":4" /><ref name=":5" /><ref name=":6" /><ref name=":8" /><ref name=":17" /><ref name=":18" /><ref>Tiu RV, LP Gondek, CL O'Keefe, Huh J, MA Sekeres, P Elson, MAMcDevitt, Wang XF, MJ Levis, JE Karp, AS Advani, JP Maciejewski. New lesions detected by single nucleotide polymorphism array-based chromosomal analysis have important clinical impact in acute myeloid leukemia. J Clin Oncol Off J Am Soc Clin Oncol, 27 (2009), pp. 5219-5226, [https://www.ncbi.nlm.nih.gov/pubmed/19770377 PMID 19770377]</ref><ref>Serrano E, Carnicer MJ, Orantes V, Estivill C, Lasa A, Brunet S, Aventin AM, Sierra J, Nomdedeu JF. Uniparental disomy may be associated with microsatellite instability in acute myeloid leukemia (AML) with a normal karyotype. Leukem Lymph 2008;49:1178–83, [https://www.ncbi.nlm.nih.gov/pubmed/18452069 PMID 18452069]</ref><ref>Koh KN, Lee JO, Seo EJ, Lee SW, Suh JK, Im HJ, Seo JJ. Clinical significance of previously cryptic copy number alterations and loss of heterozygosity in pediatric acute myeloid leukemia and myelodysplastic syndrome determined using combined array comparative genomic hybridization plus single nucleotide polymorphism microarray analyses. J Korean Med Sci 2014;29:926–33, [https://www.ncbi.nlm.nih.gov/pubmed/25045224 PMID 25045224]</ref><ref>Stirewalt DL, Pogosova-Agadjanyan EL, Tsuchiya K, Joaquin J, Meshinchi S. Copy neutral loss of heterozygosity is prevalent and a late event in the pathogenesis of FLT3/ITD AML.Blood Cancer J 2014;4:e208, [https://www.ncbi.nlm.nih.gov/pubmed/24786392 PMID 24786392]</ref>
|-
|-
| 16
|16
| NK-AML, AML w complex karyotype, pAML, sAML
|NK-AML, AML with complex karyotype, pAML, sAML
| Loss
|Loss
| 16q
|16q
| ''CBFB''
|''[[CBFB]]''
| D
|D
| 3
|3
| [29, 49, 61, 108]
|<ref name=":1" /><ref name=":11" /><ref name=":16" /><ref name=":25" />
|-
|-
| 17
|17
| AML, NK-AML, pAML, sAML
|AML, NK-AML, pAML, sAML
| CN-LOH
|CN-LOH
| 17p
|17p
| ''TP53''
|''[[TP53]]''
| D
|D
| 3
|3
| [11, 28, 29, 65, 67, 102, 107]
|<ref name=":0" /><ref name=":1" /><ref name=":3" /><ref name=":4" /><ref name=":6" /><ref name=":24" /><ref name=":18" />
|-
|-
| 17
|17
| sAML, NK-AML, AML w complex karyotype, de novo AML
|sAML, NK-AML, AML with complex karyotype, ''de novo'' AML
| Loss
|Loss
| 17p
|17p
| ''TP53''
|''[[TP53]]''
| D, P
|D, P
| 1
|1
| [24, 28, 29, 49, 61, 66, 88, 106-108, 114]
|<ref name=":1" /><ref name=":10" /><ref name=":8" /><ref name=":11" /><ref name=":22" /><ref name=":23" /><ref name=":24" /><ref name=":16" /><ref name=":18" /><ref name=":25" /><ref name=":26" />
|-
|-
| 17
|17
| NK-AML, pAML
|NK-AML, pAML
| Loss
|Loss
| 17q11.2
|17q11.2
| ''NF1, SUZ12''
|''[[NF1]], [[SUZ12]]''
| D, P
|D, P
| 3
|3
| [24, 28, 29, 47-49, 61, 66, 104, 111]
|<ref name=":1" /><ref name=":5" /><ref name=":8" /><ref name=":10" /><ref name=":11" /><ref name=":18" /><ref name=":25" /><ref name=":19" /><ref>C Haferlach, V Grossmann, A Kohlmann, S Schindela, W Kern, SSchnittger, T Haferlach. Deletion of the tumor-suppressor gene NF1 occurs in 5% of myeloid malignancies and is accompanied by a mutation in the remaining allele in half of the cases. Leukemia, 26 (2012), pp. 834-839, [https://www.ncbi.nlm.nih.gov/pubmed/22015770 PMID 22015770]</ref><ref>Boudry-Labis E, Roche-Lestienne C, Niboure lO, Boisse lN, Terre C, Perot C, Eclache V, Gachard N, Tigaud I, Plessis G, Cuccuini W, Geffroy S, Villenet C, Figeac M, Lepretre F, Renneville A, Cheok M, Soulier J, Dombret H, Preudhomme C, Ag F. Neurofibromatosis-1 gene deletions and mutations in de novo adult acute myeloid leukemia. Am J Hematol 2013;88:306–11, [https://www.ncbi.nlm.nih.gov/pubmed/23460398 PMID 23460398]</ref>
|-
|-
| 19*
|19*
| AML, NK-AML, sAML
|AML, NK-AML, sAML
| CN-LOH
|CN-LOH
| 19q
|19q
| ''CEBPA''
|''[[CEBPA]]''
| D
|D
| 3
|3
| [11, 29, 30, 69, 102, 105]
|<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":13" /><ref name=":4" /><ref name=":21" />
|-
|-
| 20
|20
| sAML
|sAML
| Loss
|Loss
| 20q
|20q
|
|
| D
|D
| 3
|3
| [24, 66, 119, 120]
|<ref name=":8" /><ref name=":10" /><ref>Barresi V, Palumbo GA, Musso N, Consoli C, Capizzi C, Meli CR, Romano A, DiRaimondo F, Condorelli DF. Clonal selection of 11q CN-LOH and CBL gene mutation in a serially studied patient during MDS progression to AML. Leukemia Res 2010;34:1539–42, [https://www.ncbi.nlm.nih.gov/pubmed/20674974 PMID 20674974]</ref><ref>Huh J, Tiu RV, Gondek LP, O’Keefe CL, Jasek M, Makishima H, Jankowska AM, Jiang Y, Verma A, Theil KS, McDevitt MA, Maciejewski JP. Characterization of chromosome arm 20q abnormalities in myeloid malignancies using genome-wide single nucleotide polymorphism array analysis. Genes Chromos Cancer 2010;49:390–9, [https://www.ncbi.nlm.nih.gov/pubmed/20095039 PMID 20095039]</ref>
|-
|-
| 21*
|21*
| pAML, AML w complex karyotype
|pAML, AML with complex karyotype
| Amplification
|Amplification
| 21q22
|21q22
| ''ERG, ETS2''
|''[[ERG]], [[ETS2]]''
| D, P, T
|D, P, T
| 3
|3
| [49, 57, 61, 62, 121]
|<ref name=":7" /><ref name=":11" /><ref name=":25" /><ref>O Nibourel, S Guihard, C Roumier, N Pottier, C Terre, A Paquet, PPeyrouze, S Geffroy, S Quentin, A Alberdi, RB Abdelali, ARenneville, C Demay, K Celli-Lebras, P Barbry, B Quesnel, SCastaigne, H Dombret, J Soulier, C Preudhomme, MH Cheok. Copy-number analysis identified new prognostic marker in acute myeloid leukemia. Leukemia, 31 (2017), pp. 555-564, [https://www.ncbi.nlm.nih.gov/pubmed/27686867 PMID 27686867]</ref><ref>CD Baldus, S Liyanarachchi, K Mrozek, H Auer, SM Tanner, MGuimond, AS Ruppert, N Mohamed, RV Davuluri, MA Caligiuri, CD Bloomfield, A de la Chapelle. Acute myeloid leukemia with complex karyotypes and abnormal chromosome 21: amplification discloses overexpression of APP, ETS2, and ERG genes. Proc Natl Acad Sci USA, 101 (2004), pp. 3915-3920, [https://www.ncbi.nlm.nih.gov/pubmed/15007164 PMID 15007164]</ref>
|-
|-
| 21*
|21*
| AML, NK-AML, sAML
|AML, NK-AML, sAML
| CN-LOH
|CN-LOH
| 21q
|21q
| ''RUNX1''
|''[[RUNX1]]''
| D
|D
| 3
|3
| [11, 29, 67, 70, 102-105]
|<ref name=":0" /><ref name=":1" /><ref name=":3" /><ref name=":4" /><ref name=":20" /><ref name=":5" /><ref name=":21" /><ref>FP Silva, I Almeida, B Morolli, G Brouwer-Mandema, H Wessels, RVossen, H Vrieling, EW Marijt, PJ Valk, HC Kluin-Nelemans, WRSperr, WD Ludwig, M Giphart-Gassler. Genome wide molecular analysis of minimally differentiated acute myeloid leukemia. Haematologica, 94 (2009), pp. 1546-1554, [https://www.ncbi.nlm.nih.gov/pubmed/19773259 PMID 19773259]</ref>
|-
|-
| 21*
|21*
| sAML
|sAML
| Loss
|Loss
| 21q22.12
|21q22.12
| ''RUNX1''
|''[[RUNX1]]''
| D
|D
| 3
|3
| [57]
|<ref name=":7" />
|-
|-
|}
|}
D- diagnostic significance; P-prognostic significance; T- therapeutic significance. Classification of levels of evidence: Level 1- WHO classification or professional practice guidelines; Level 2- well-powered studies with consensus from experts in the field; Level 3- multiple small studies without any contradicting data; Level 4- individual small studies, case reports, preclinical studies.
D = diagnostic significance; P = prognostic significance; T = therapeutic significance. Classification of levels of evidence: Level 1 = WHO classification or professional practice guidelines; Level 2 = well-powered studies with consensus from experts in the field; Level 3 = multiple small studies without any contradicting data; Level 4 = individual small studies, case reports, preclinical studies.
CMA indicates chromosomal microarray; CNA indicates copy number aberration; CN-LOH indicates copy-neutral loss-of-heterozygosity; AML indicates acute myeloid leukemia; NK-AML indicates normal karyotype AML; pAML indicates primary AML; and sAML indicates secondary AML.
Abrreviations: CMA = chromosomal microarray; CNA = copy number aberration; CN-LOH = copy-neutral loss-of-heterozygosity; AML = acute myeloid leukemia; NK-AML = normal karyotype AML; pAML = primary AML; and sAML = secondary AML.
The * indicates CNAs and CN-LOH regions that are predominantly seen in AML.
The * indicates CNAs and CN-LOH regions that are predominantly seen in AML.
==References==
==Reference==
1. Xu X, Bryke C, Sukhanova M, Huxley E, Dash DP, Dixon-Mciver A, Fang M, Griepp PT, Hodge JC, Iqbal A, Jeffries S, Kanagal-Shamanna R, Quintero-Rivera F, Shetty S, Slovak ML, Yenamandra A, Lennon PA, Raca G. (2018). Assessing copy number abnormalities and copy-neutral loss-of-heterozygosity across the genome as best practice in diagnostic evaluation of acute myeloid leukemia: An evidence-based review from the cancer genomics consortium (CGC) myeloid neoplasms working group. Cancer Genet [Epub ahead of print], PMID 30344013.
1. Xu X, Bryke C, Sukhanova M, Huxley E, Dash DP, Dixon-Mciver A, Fang M, Griepp PT, Hodge JC, Iqbal A, Jeffries S, Kanagal-Shamanna R, Quintero-Rivera F, Shetty S, Slovak ML, Yenamandra A, Lennon PA, Raca G. (2018). Assessing copy number abnormalities and copy-neutral loss-of-heterozygosity across the genome as best practice in diagnostic evaluation of acute myeloid leukemia: An evidence-based review from the cancer genomics consortium (CGC) myeloid neoplasms working group. Cancer Genet [Epub ahead of print], PMID 30344013.
<references />