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In Reply

Department of Internal Medicine III, University of Ulm, Ulm, Germany

Suela et al profiled a series of 120 unselected de novo acute myeloid leukemia (AML) patients including all cytogenetic subgroups for genomic imbalances using a high density oligonucleotide-based array comparative genomic hybridization platform. Using this approach, they identified seven patients, two patients with inversion 16 (inv (16)) and five patients with complex karyotypes, that showed cryptic genomic deletions in chromosomal band 17q11.2 encompassing neurofibromastosis 1 (NF1). Of these patients only two exhibited concomitant deletions affecting TP53. In addition, the authors performed loss of heterozygosity analyses revealing one patient with loss of heterozygosity affecting the genomic region of TP53. Furthermore, sequence analyses of TP53 (exons 4 through 9) disclosed two patients with additional TP53 alterations (one patient was heterozygous for the mutation, the other one had lost the wild type allele of TP53). Thus, in four of seven 17q11.2 deleted patients TP53 aberrations were present, and interestingly all of these were AML patients with complex karyotypes.

We greatly appreciate the comments by Suela and colleagues confirming our findings that NF1 may be a target of chromosome 17 rearrangements. In our recent study comprising 60 AML patients with complex karyotypes, genomic deletions of 17p13 encompassing TP53 were more common than deletions harboring NF1 (55% v 30%).² Suela and colleagues analyzed 120 unselected patients of de novo AML; with a general incidence of 15%, the series probably included about 15 patients with complex karyotypes (the number was not provided). We believe that such low numbers do not allow a reliable determination of the incidence of genetic lesions. Subgroup-specific analyses in our series of 60 complex karyotypes AML patients (younger [age < 60 years] de novo AML [n = 7], younger secondary [post-myelodysplastic syndrome and therapy-related] AML [n = 6], elderly [age 60 years] de novo AML [n = 13], and elderly secondary AML patients [n = 5]) disclosed deletions of 17p13 encompassing TP53 in all subsets as the main chromosome 17 aberration. Our data support the finding that NF1 deletion may occur without TP53 alteration. We recently identified two additional patients with isolated 17q11.2 loss without concomitant 17p13 deletion. We were able to further narrow down the minimally deleted fragment to approximately 800 kb in size harboring NF1. Sequence analysis of TP53 (exons 4 through 9) showed that in one of these patients no TP53 mutation was present.

An intriguing finding of the study by Suela et al is that 17q11.2 deletions may also occur in other cytogenetic subgroups as shown by isolated 17q11.2 deletion as secondary change in two patients with inv (16).

In summary, our data and that by Suela et al are in agreement in showing that NF1 may be a target of chromosome 17 rearrangements with or without TP53 alteration. NF1 deletions seem to be most prevalent in AML with complex karyotypes. Future analyses including the investigation of uniparentaldisomy³ might help to further unravel the involvement of these genomic regions in myeloid leukemogenesis.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The authors indicated no potential conflicts of interest.

ACKNOWLEDGMENTS

This study was supported by Bundesministerium für Bildung und Forschung Grant No. 01GS0439 NGFN2.

REFERENCES

1. Rücker FG, Bullinger L, Schwaenen C, et al: Disclosure of candidate genes in acute myeloid leukemia with complex karyotypes using microarray-based molecular characterization. J Clin Oncol 24:3887-3894, 2006[Abstract/Free Full Text]

2. Stephens K, Weaver M, Leppig KA, et al: Interstitial uniparental isodisomy at clustered breakpoint intervals is a frequent mechanism of NF1 inactivation in myeloid malignancies. Blood 108:1684-1689, 2006[Abstract/Free Full Text]

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Related Correspondence

• Neurofibromatosis 1, and Not TP53, Seems to Be the Main Target of Chromosome 17 Deletions in De Novo Acute Myeloid Leukemia
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