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Clinical impact of internal tandem duplications and activating point mutations in FLT3 in acute myeloid leukemia in elderly patients.
Eur J Haematol. 2004 May; 72(5):307-13.EJ

Abstract

BACKGROUND

The FLT3 gene is frequently mutated in acute myeloid leukemia (AML), either by an internal tandem duplication (ITD) of the juxtamembrane domain or by activating point mutations in the second tyrosine kinase domain (ATKD). Only a few investigations have focused on the prognostic significance of FLT3 alterations in AML among the elderly, yielding conflicting results. In the present study, the frequency and clinical relevance of FLT3 abnormalities were ascertained in a cohort of elderly AML patients.

PATIENTS AND METHODS

A total of 109 AMLs, occurring in patients above the age of 60 yr (median 71.5), were investigated. DNA was extracted from fresh bone marrow cells or from cells in fixative and investigated for the presence of ITD of exons 14 and 15 and the ATKD D835 in exon 20.

RESULTS

ITDs and ATKDs were identified in 20 (18%) and 11 (10%) of the cases, respectively. Three cases displayed both an ITD and an ATKD. FLT3 abnormalities were associated with leukocytosis (ITD P < 0.01; ATKD P = 0.069), and the monocytic FAB subtypes M4 and M5 [ITD (P < 0.05), ATKD (P = 0.05)], and ITD and ATKD were significantly (P < 0.05) more common in cases with a normal karyotype. There was no correlation between the presence of FLT3 abnormalities and complete remission rates or overall survival.

CONCLUSION

A correlation was observed between FLT3 abnormalities and leukocytosis, a normal karyotype, and the M4/M5 subtypes of leukemia. However, no clear-cut prognostic impact of FLT3 abnormalities was identified in elderly AML patients.

Authors+Show Affiliations

Andersson A
Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden. anna.andersson@klingen.lu.se
Johansson B
No affiliation info available
Lassen C
No affiliation info available
Mitelman F
No affiliation info available
Billström R
No affiliation info available
Fioretos T
No affiliation info available

MeSH

Acute DiseaseAgedDNA, NeoplasmExonsFemaleHumansInclusion BodiesLeukemia, Monocytic, AcuteLeukemia, MyeloidLeukemia, Myelomonocytic, AcuteLeukocyte CountMaleMiddle AgedNeoplasm ProteinsPoint MutationPrognosisProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSurvival AnalysisTandem Repeat Sequencesfms-Like Tyrosine Kinase 3

Pub Type(s)

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

Language

eng

PubMed ID

15059064

Citation

Andersson, Anna, et al. "Clinical Impact of Internal Tandem Duplications and Activating Point Mutations in FLT3 in Acute Myeloid Leukemia in Elderly Patients." European Journal of Haematology, vol. 72, no. 5, 2004, pp. 307-13.
Andersson A, Johansson B, Lassen C, et al. Clinical impact of internal tandem duplications and activating point mutations in FLT3 in acute myeloid leukemia in elderly patients. Eur J Haematol. 2004;72(5):307-13.
Andersson, A., Johansson, B., Lassen, C., Mitelman, F., Billström, R., & Fioretos, T. (2004). Clinical impact of internal tandem duplications and activating point mutations in FLT3 in acute myeloid leukemia in elderly patients. European Journal of Haematology, 72(5), 307-13.
Andersson A, et al. Clinical Impact of Internal Tandem Duplications and Activating Point Mutations in FLT3 in Acute Myeloid Leukemia in Elderly Patients. Eur J Haematol. 2004;72(5):307-13. PubMed PMID: 15059064.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical impact of internal tandem duplications and activating point mutations in FLT3 in acute myeloid leukemia in elderly patients. AU - Andersson,Anna, AU - Johansson,Bertil, AU - Lassen,Carin, AU - Mitelman,Felix, AU - Billström,Rolf, AU - Fioretos,Thoas, PY - 2004/4/3/pubmed PY - 2004/5/18/medline PY - 2004/4/3/entrez SP - 307 EP - 13 JF - European journal of haematology JO - Eur J Haematol VL - 72 IS - 5 N2 - BACKGROUND: The FLT3 gene is frequently mutated in acute myeloid leukemia (AML), either by an internal tandem duplication (ITD) of the juxtamembrane domain or by activating point mutations in the second tyrosine kinase domain (ATKD). Only a few investigations have focused on the prognostic significance of FLT3 alterations in AML among the elderly, yielding conflicting results. In the present study, the frequency and clinical relevance of FLT3 abnormalities were ascertained in a cohort of elderly AML patients. PATIENTS AND METHODS: A total of 109 AMLs, occurring in patients above the age of 60 yr (median 71.5), were investigated. DNA was extracted from fresh bone marrow cells or from cells in fixative and investigated for the presence of ITD of exons 14 and 15 and the ATKD D835 in exon 20. RESULTS: ITDs and ATKDs were identified in 20 (18%) and 11 (10%) of the cases, respectively. Three cases displayed both an ITD and an ATKD. FLT3 abnormalities were associated with leukocytosis (ITD P < 0.01; ATKD P = 0.069), and the monocytic FAB subtypes M4 and M5 [ITD (P < 0.05), ATKD (P = 0.05)], and ITD and ATKD were significantly (P < 0.05) more common in cases with a normal karyotype. There was no correlation between the presence of FLT3 abnormalities and complete remission rates or overall survival. CONCLUSION: A correlation was observed between FLT3 abnormalities and leukocytosis, a normal karyotype, and the M4/M5 subtypes of leukemia. However, no clear-cut prognostic impact of FLT3 abnormalities was identified in elderly AML patients. SN - 0902-4441 UR - https://www.unboundmedicine.com/medline/citation/15059064/Clinical_impact_of_internal_tandem_duplications_and_activating_point_mutations_in_FLT3_in_acute_myeloid_leukemia_in_elderly_patients_ DB - PRIME DP - Unbound Medicine ER -