Characteristics and Prognosis of Adult Acute Myeloid Leukemia with Internal Tandem Duplication in the FLT3 Gene

Adhra Al-Mawali; David Gillis; Ian Lewis

doi:10.5001/omj.2013.121

Article Details

Characteristics and Prognosis of Adult Acute Myeloid Leukemia with Internal Tandem Duplication in the FLT3 Gene

Authors:

Adhra Al-Mawali | David Gillis | Ian Lewis

Publisher:

Oman Medical Specialty Board

Main Topics:

Medicine

Journal:

Oman Medical Journal 2013 vol.28 Issue 6, pp.432-440

Document Type:

Article

Publication Date:

11/2013

Document Language:

English

Document ID (Org No.):

39095

Frequency:

Bi-Monthly

eISSN:

20705204

pISSN:

1999768X

DOI:

10.5001/omj.2013.121

Descriptors:

Keywords:

Abstract:

 Objectives: Constitutive activation of the fms-like tyrosine kinase3 (FLT3) receptor by internal tandem duplication (ITD) of thejuxtamembrane region has been described in patients with acutemyeloid leukemia. FLT3/ITDs are present in about 20-30% of allacute myeloid leukemia cases. It has been shown that the mutationis correlated with worse prognosis. However, none of the previousstudies investigated which FAB subtype is associated with higherpercentage of FLT3/ITD, thus the reason for undertaking thecurrent study.Methods: The prevalence and the potential prognostic impactof FLT3 mutations in 39 acute myeloid leukemia patients wereanalyzed by genomic polymerase chain reaction. Twelve sampleswith FLT3/ITDs and 27 acute myeloid leukemia samples withoutthe mutations were compared with respect to clinical prognosis andFAB subtype. Results were correlated with cytogenetic data and theclinical response.Results: FLT3/ITD mutations were found in 31% of patients.FLT3/ITD was associated with similar clinical characteristicsand was more prevalent in patients with normal karyotype (83%).Interestingly, half of the FLT3/ITD aberrations were found inpatients with FAB M1 (50%), and fewer were found in patientswith FAB M2 (8%), M4 (8%), and M5 (8%). Although less frequentin patients with cytogenetic aberrations, FLT3/ITDs were foundin 17% of patients with t(15;17). Although the study was poweredto 80%, patients with FLT3/ITD mutation did not show shortercomplete remission duration or a higher relapse rate.Conclusion: The data confirm that FLT3/ITD mutations representa common alteration in adult acute myeloid leukemia, mainly withnormal karyotype (83%) and de novo acute myeloid leukemia (75%),as compared to secondary acute myeloid leukemia (25%) (p<0.001).It also showed that half of the M1-FAB subtype is FLT3/ITDpositive. Therefore, FLT3/ITD is a therapeutic target, and thusinhibition of FLT3 tyrosine kinase activity may provide a newapproach in the treatment of leukemia carrying these mutations.

Article Details

Characteristics and Prognosis of Adult Acute Myeloid Leukemia with Internal Tandem Duplication in the FLT3 Gene

Authors:

Adhra Al-Mawali | David Gillis | Ian Lewis

Publisher:

Oman Medical Specialty Board

Main Topics:

Medicine

Journal:

Oman Medical Journal 2013 vol.28 Issue 6, pp.432-440

Document Type:

Article

Publication Date:

11/2013

Document Language:

English

Document ID (Org No.):

39095

Frequency:

Bi-Monthly

eISSN:

20705204

pISSN:

1999768X

DOI:

10.5001/omj.2013.121

Descriptors:

DISEASES

NEOPLASMS

LEUKEMIA

CLINICAL EXAMINATIONS

BONE MARROW

DIAGNOSIS

MUTATION

PATIENTS

THERAPY

Acute Myeloid Leukemia

M1

FLT3 gene

Tandem duplication

Prognosis

Issues

Article Details

Authors: Adhra Al-Mawali | David Gillis | Ian Lewis

Publisher: Oman Medical Specialty Board

Main Topics: Medicine

Journal: Oman Medical Journal 2013 vol.28 Issue 6, pp.432-440

Document Type: Article

Publication Date: 11/2013

Document Language: English

Document ID (Org No.): 39095

Frequency: Bi-Monthly

eISSN: 20705204

pISSN: 1999768X

DOI: 10.5001/omj.2013.121

Descriptors:

Issues

Authors:

Adhra Al-Mawali | David Gillis | Ian Lewis

Publisher:

Oman Medical Specialty Board

Main Topics:

Medicine

Journal:

Oman Medical Journal 2013 vol.28 Issue 6, pp.432-440

Document Type:

Article

Publication Date:

11/2013

Document Language:

English

Document ID (Org No.):

39095

Frequency:

Bi-Monthly

eISSN:

20705204

pISSN:

1999768X

DOI:

10.5001/omj.2013.121