Originally published as JCO Early Release 10.1200/JCO.2008.19.3011 on December 15 2008

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Medeiros, B. C. Search for Related Content PubMed PubMed Citation Articles by Medeiros, B. C. Related Articles Related Reply Related Article Social Bookmarking                            What's this?

Comparing Apples and Oranges in Normal Karyotype Acute Myeloid Leukemia

Bruno C. Medeiros

Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA

To the Editor:

Several recent reports have demonstrated the prognostic impact of NPM1, FLT3, and CEBP on the outcome of treatment for patients with normal karyotype acute myeloid leukemia (NK-AML).^1,2 Specifically, these reports define two distinct groups of patients—those with NPM1 mutations without FLT3 internal tandem duplications (FLT3-ITDs), and those with CEBP mutations—who have improved disease-free and overall survival. The recent articles by Virappane et al³ and Paschka et al⁴ add to the list of molecularly relevant prognostic markers in NK-AML. These authors report the results of the prognostic impact of Wilms<5002> tumor 1 (WT1) gene mutations in patients with NK-AML. Although there were minor discrepancies between their results, both articles report a similar incidence of WT1 mutations, comparable distribution of mutations on the WT1 gene, and similar impact of WT1 mutations in disease-free survival and overall survival, which were independent of known prognostic factors in NK-AML, such as FLT3-ITD and NPM1 mutational status. Interestingly, Paschka et al also report the potential negative impact of WT1 mutations on the small group considered to have a lower risk of relapse (NPM1^mutant/FLT3-ITD^wt [where wt indicates wild type]). Although the cohort analyzed was small, confirmation of these results would have significant clinical impact on molecular-based risk stratification algorithms, because they suggest WT1 mutations may overcome the favorable prognostic impact of NPM1^mutant/FLT3-ITD^wt in NK-AML. Unfortunately, Virappane et al only analyzed the independent prognostic value of WT1 mutations in relation to either FLT3-ITDs or NPM1 mutations. Given their larger patient cohort, and in light of the results reported by Paschka et al, it is important to assess whether WT1 mutations remain an independent negative prognostic indicator in patients of a low-risk molecular category (NPM1^mutant/FLT3-ITD^wt) compared with molecularly high-risk patients. These findings could have immediate clinical impact on risk-stratified treatment decisions.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

NOTES

published online ahead of print at www.jco.org on December 15, 2008

REFERENCES

1. Schlenk RF, Döhner K, Krauter J, et al: Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med 358:1909-1918, 2008[Abstract/Free Full Text]

2. Döhner K, Schlenk RF, Habdank M, et al: Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: Interaction with other gene mutations. Blood 106:3740-3746, 2005[Abstract/Free Full Text]

3. Virappane P, Gale R, Hills R, et al: Mutation of the Wilms’ tumor 1 gene is a poor prognostic factor associated with chemotherapy resistance in normal karyotype acute myeloid leukemia: The United Kingdom Medical Research Council Adult Leukaemia Working Party. J Clin Oncol doi:10.1200/JCO.2008.16.0333 [epub ahead of print on July 7, 2008][Abstract/Free Full Text]

4. Paschka P, Marcucci G, Ruppert AS, et al: Wilms’ tumor 1 gene mutations independently predict poor outcome in adults with cytogenetically normal acute myeloid leukemia: A cancer and leukemia group B study. J Clin Oncol 26:4595-4602, 2008[Abstract/Free Full Text]

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Reply

• In Reply
  Jude Fitzgibbon, Rosemary Gale, Robert Hills, Priya Virappane, Alan Burnett, T. Andrew Lister, and David Linch
  JCO 2009 27: 474-476 [Full Text]

Related Article

• Wilms’ Tumor 1 Gene Mutations Independently Predict Poor Outcome in Adults With Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study
  Peter Paschka, Guido Marcucci, Amy S. Ruppert, Susan P. Whitman, Krzysztof Mrózek, Kati Maharry, Christian Langer, Claudia D. Baldus, Weiqiang Zhao, Bayard L. Powell, Maria R. Baer, Andrew J. Carroll, Michael A. Caligiuri, Jonathan E. Kolitz, Richard A. Larson, and Clara D. Bloomfield
  JCO 2008 26: 4595-4602 [Abstract] [Full Text]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Medeiros, B. C. Search for Related Content PubMed PubMed Citation Articles by Medeiros, B. C. Related Articles Related Reply Related Article Social Bookmarking                            What's this?