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Risk assessment in patients with acute myeloid leukemia and a normal karyotype.
Clin Cancer Res. 2005 Feb 15; 11(4):1416-24.CC

Abstract

PURPOSE

The recognition of a number of leukemia-specific cytogenetic abnormalities and their role as independent prognostic factors have provided considerable insights into leukemia pathogenesis and have paved the way to adopt risk-adapted treatment. However, approximately 50% of newly diagnosed acute myeloid leukemia (AML) have a normal karyotype. There has therefore been much interest in identifying molecular markers that could help to improve the prognostic stratification of patients with normal-karyotype AML.

EXPERIMENTAL DESIGN

Consecutive untreated AML patients (n = 67) from a single institution all with normal karyotype were analyzed for the presence of mutations in the myeloid transcription factor gene CEBPA (for CCAAT/enhancer binding protein-alpha), for internal tandem duplications (ITD) of the tyrosine kinase receptor gene FLT3 (for fms-like tyrosine kinase 3), and for expression of the BAALC gene (for brain and acute leukemia, cytoplasmic).

RESULTS

17.9% of normal-karyotype AML had mutations in the CEBPA gene, and 28.4% had FLT3-ITD; 65.7% (44 of 67) had high BAALC expression and 34.3% (23 of 67) had low BAALC expression. Patients with CEBPA mutations had a very favorable course of their disease. Median disease-free survival (DFS) and overall survival (OS) were 33.5 and 45.5 months, respectively, compared with 10 (e.g., 12 months in patients without CEBPA mutations; P = 0.0017; P = 0.0007). AML patients with FLT3-ITD had significantly shorter median DFS (P = 0.0328) and OS (P = 0.0148) than patients without FLT3-ITD. High BAALC expression predicted for a shorter DFS (P = 0.0152) and OS (P = 0.0210) compared with AML with low BAALC expression; 53.7% of normal-karyotype AML had neither FLT3-ITD nor CEBPA mutations. We found that high BAALC expression in normal-karyotype AML with neither FLT3-ITD nor CEBPA mutations (18 of 67) indicates adverse prognosis for both DFS and OS (P = 0.0001; e.g., P = 0.0001) compared with the group with low BAALC expression and absent FLT3-ITD and CEBPA mutations (18 of 67). Thus, BAALC expression represents a novel prognostic marker particularly for normal-karyotype AML patients with neither FLT3-ITD nor CEBPA mutations.

CONCLUSIONS

Assessment of CEBPA mutations, FLT3-ITD, and BAALC expression permits to split normal-karyotype AML into clinically distinct subgroups.

Authors+Show Affiliations

Institute of Medical Oncology and the Laboratory for Molecular Diagnostics, Department of Hematology, University of Berne, CH-3010 Berne, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15746041

Citation

Bienz, Marianne, et al. "Risk Assessment in Patients With Acute Myeloid Leukemia and a Normal Karyotype." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 11, no. 4, 2005, pp. 1416-24.
Bienz M, Ludwig M, Leibundgut EO, et al. Risk assessment in patients with acute myeloid leukemia and a normal karyotype. Clin Cancer Res. 2005;11(4):1416-24.
Bienz, M., Ludwig, M., Leibundgut, E. O., Mueller, B. U., Ratschiller, D., Solenthaler, M., Fey, M. F., & Pabst, T. (2005). Risk assessment in patients with acute myeloid leukemia and a normal karyotype. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 11(4), 1416-24.
Bienz M, et al. Risk Assessment in Patients With Acute Myeloid Leukemia and a Normal Karyotype. Clin Cancer Res. 2005 Feb 15;11(4):1416-24. PubMed PMID: 15746041.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Risk assessment in patients with acute myeloid leukemia and a normal karyotype. AU - Bienz,Marianne, AU - Ludwig,Madleina, AU - Leibundgut,Elisabeth Oppliger, AU - Mueller,Beatrice U, AU - Ratschiller,Daniel, AU - Solenthaler,Max, AU - Fey,Martin F, AU - Pabst,Thomas, PY - 2005/3/5/pubmed PY - 2005/7/29/medline PY - 2005/3/5/entrez SP - 1416 EP - 24 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 11 IS - 4 N2 - PURPOSE: The recognition of a number of leukemia-specific cytogenetic abnormalities and their role as independent prognostic factors have provided considerable insights into leukemia pathogenesis and have paved the way to adopt risk-adapted treatment. However, approximately 50% of newly diagnosed acute myeloid leukemia (AML) have a normal karyotype. There has therefore been much interest in identifying molecular markers that could help to improve the prognostic stratification of patients with normal-karyotype AML. EXPERIMENTAL DESIGN: Consecutive untreated AML patients (n = 67) from a single institution all with normal karyotype were analyzed for the presence of mutations in the myeloid transcription factor gene CEBPA (for CCAAT/enhancer binding protein-alpha), for internal tandem duplications (ITD) of the tyrosine kinase receptor gene FLT3 (for fms-like tyrosine kinase 3), and for expression of the BAALC gene (for brain and acute leukemia, cytoplasmic). RESULTS: 17.9% of normal-karyotype AML had mutations in the CEBPA gene, and 28.4% had FLT3-ITD; 65.7% (44 of 67) had high BAALC expression and 34.3% (23 of 67) had low BAALC expression. Patients with CEBPA mutations had a very favorable course of their disease. Median disease-free survival (DFS) and overall survival (OS) were 33.5 and 45.5 months, respectively, compared with 10 (e.g., 12 months in patients without CEBPA mutations; P = 0.0017; P = 0.0007). AML patients with FLT3-ITD had significantly shorter median DFS (P = 0.0328) and OS (P = 0.0148) than patients without FLT3-ITD. High BAALC expression predicted for a shorter DFS (P = 0.0152) and OS (P = 0.0210) compared with AML with low BAALC expression; 53.7% of normal-karyotype AML had neither FLT3-ITD nor CEBPA mutations. We found that high BAALC expression in normal-karyotype AML with neither FLT3-ITD nor CEBPA mutations (18 of 67) indicates adverse prognosis for both DFS and OS (P = 0.0001; e.g., P = 0.0001) compared with the group with low BAALC expression and absent FLT3-ITD and CEBPA mutations (18 of 67). Thus, BAALC expression represents a novel prognostic marker particularly for normal-karyotype AML patients with neither FLT3-ITD nor CEBPA mutations. CONCLUSIONS: Assessment of CEBPA mutations, FLT3-ITD, and BAALC expression permits to split normal-karyotype AML into clinically distinct subgroups. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/15746041/Risk_assessment_in_patients_with_acute_myeloid_leukemia_and_a_normal_karyotype_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15746041 DB - PRIME DP - Unbound Medicine ER -