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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

Bienz M
Institute of Medical Oncology and the Laboratory for Molecular Diagnostics, Department of Hematology, University of Berne, CH-3010 Berne, Switzerland.
Ludwig M
No affiliation info available
Leibundgut EO
No affiliation info available
Mueller BU
No affiliation info available
Ratschiller D
No affiliation info available
Solenthaler M
No affiliation info available
Fey MF
No affiliation info available
Pabst T
No affiliation info available

MeSH

Acute DiseaseAdolescentAdultAgedAntigens, CDCCAAT-Enhancer-Binding Protein-alphaDNA Mutational AnalysisFemaleGene Expression Regulation, NeoplasticHumansImmunophenotypingKaryotypingLeukemia, MyeloidMaleMiddle AgedMutationNeoplasm ProteinsPrognosisProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesRisk AssessmentSurvival Analysisfms-Like Tyrosine Kinase 3

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_ DB - PRIME DP - Unbound Medicine ER -