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.
| Chromosome | AML Subtype | Abnormality Type (Gain, Loss, CN-LOH) | Region | Relevant Genes (if known) | Clinical Significance | Level of Evidence | Reference |
|---|---|---|---|---|---|---|---|
| 1 | AML including NK-AML | CN-LOH | 1p | D | 3 | [11, 29, 30, 67-69, 102-104] | |
| 2 | AML | CN-LOH | 2p | DNMT3A | D | 3 | [11, 65, 100] |
| 3 | NK-AML, sAML | Loss | 3p14.1 | FOXP1 | D | 3 | [30, 57, 66] |
| 4 | sAML, pAML | CN-LOH | 4q24 | TET2 | D | 3 | [67, 71, 105] |
| 4 | AML, NK-AML, sAML | Loss | 4q24 | TET2 | D, P | 3 | [42, 45, 66] |
| 5 | pAML, sAML | Loss | 5q | D | 1 | [24, 33, 45, 49, 57, 66, 77, 87, 88, 106-108] | |
| 6 | AML including NK-AML | CN-LOH | 6p | D | 3 | [29, 30, 102, 104] | |
| 7 | AML including NK-AML | CN-LOH | 7q | EZH2 | D | 3 | [67, 102, 109] |
| 7 | NK-AML, pAML, sAML | Loss | 7q | EZH2, CUX1 | D | 1 | [28, 57, 66, 110] |
| 8 | complex karyotype AML | Amplification | 8q24 | MYC | D, P | 3 | [24, 49, 61] |
| 9 | NK-AML, sAML | CN-LOH | 9p | JAK2 | D | 3 | [66, 67, 104] |
| 11* | AML w complex karyotype | Amplification | 11q23 | MLL (KMT2A) | D, P | 3 | [49, 111] |
| 11* | AML | CN-LOH | 11p | WT1 | D | 3 | [11, 30, 65, 102] |
| 11 | pAML, sAML, NK-AML | CN-LOH | 11q | CBL | D | 3 | [11, 65-67, 102] |
| 12 | AML, NK-AML, AML w complex karyotype, sAML | Loss | 12p13.2 | ETV6 | D | 3 | [24, 30, 33, 49, 57, 61, 66, 77, 104, 108, 111-115] |
| 13* | pAML, NK-AML, NPM1 mutated AML, FLT3-ITD pos AML, sAML | CN-LOH | 13q | FLT3 | D, P | 2 | [11, 28-31, 65-69, 102, 104, 109, 116-118] |
| 16 | NK-AML, AML w complex karyotype, pAML, sAML | Loss | 16q | CBFB | D | 3 | [29, 49, 61, 108] |
| 17 | AML, NK-AML, pAML, sAML | CN-LOH | 17p | TP53 | D | 3 | [11, 28, 29, 65, 67, 102, 107] |
| 17 | sAML, NK-AML, AML w complex karyotype, de novo AML | Loss | 17p | TP53 | D, P | 1 | [24, 28, 29, 49, 61, 66, 88, 106-108, 114] |
| 17 | NK-AML, pAML | Loss | 17q11.2 | NF1, SUZ12 | D, P | 3 | [24, 28, 29, 47-49, 61, 66, 104, 111] |
| 19* | AML, NK-AML, sAML | CN-LOH | 19q | CEBPA | D | 3 | [11, 29, 30, 69, 102, 105] |
| 20 | sAML | Loss | 20q | D | 3 | [24, 66, 119, 120] | |
| 21* | pAML, AML w complex karyotype | Amplification | 21q22 | ERG, ETS2 | D, P, T | 3 | [49, 57, 61, 62, 121] |
| 21* | AML, NK-AML, sAML | CN-LOH | 21q | RUNX1 | D | 3 | [11, 29, 67, 70, 102-105] |
| 21* | sAML | Loss | 21q22.12 | RUNX1 | D | 3 | [57] |
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.
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.
References
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.
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