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Elucidating the Mechanisms of Acute Myloid Leukemia

Elucidating the Mechanisms of Acute Myloid Leukemia
A review of Neurofibromatosis 1, and not TP53, seems to be the main target of chromosome 17 deletions in de novo acute myeloid leukemia.

Note: This is a review of the published article listed below. All information, quotes, figures, methods, and findings mentioned in this review are from that article, and are the property of its authors and/or the publication in which the article originally appeared.

On the heels of research indicating that chromosome 17 aberrations may be involved in the mechanism of acute myloid leukemia, researchers in Spain (2007) sought to provide more detail on specific chromosomal changes, as well as confirm the link to disease onset. The researchers used Agilent’s high-density oligonucleotidebased array CGH (more than 44,000 probes) to confirm the existence of recurrent cryptic deletions in the area of 17q11.2, targeting the gene NF1, as suggested by previous studies. By using the high-density array, the research team found that the minimum deleted region in 17q11 was reduced down to approximately 1.5Mb. Although previous reports described that deletions of 17q11.2 were tightly associated with deletions in 17p13.1, including the TP53 gene, this study reported that less than 50% of there de novo AML samples with deletions in 17q11.2 showed either deletion or UPiD LOH among the TP53 locus. Only one patient with deletion or UPiD in TP53 showed mutations in the gene, suggesting that TP53 may not be the principal target in de novo AML, although its role has been demonstrated to be more relevant in secondary AML. The group concludes that their genetic data support the proposed role of NF1 as the main target in rearrangements of chromosome 17 in de novo AML.

Table 1. TP53 and NF1 Status in Patients With Chromosome 17 Abnormalities
Patient Karyotype TP53
 NF1
Array CGH FISH UPiD Mutation Array CGH FISH UPiD
1 inv(16) 2n 2n — — 1n 1n NA
2 Complex 2n 2n + — 1n 1n NA
3 Complex 1n 1n NA R280G 1n 1n NA
4 Complex 3n 3n — 1245gdelc 1n 1n NA
5 inv(16) 2n 2n — — 1n 1n NA
6 Complex 2n 2n — — 1n 1n NA
7 Complex 1n 1n NA — 1n 1n NA
Abbreviations: NF1, neurofibromatosis 1; CGH, comparative genomic hybridization; FISH, fluorescence in situ hybridization; UPiD, uniparental isodisomy; R, arginine; G, glycine; g, guanine; c, cytosine; NA, not assessed due to the deleted status.
Title: Neurofibromatosis 1, and Not TP53, seems to be the main target of chromosome 17 deletions in de novo acute myeloid leukemia.
Authors: Suela J, Largo C, Ferreira B, Alvarez S, Robledo M, Gonzalez-Neira A, Calasanz MJ, Cigudosa JC.
Journal: J Clin Oncol. 2006 Aug 20;24(24):3887-94.
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