Acute Myelocytic Leukemia (AML) : FLT3-ITD & FLT3-TKD Variant Analysis

Test Information

The fms-like tyrosine kinase 3 (FLT3) gene is found on chromosome 13q12 and totals 24 exons. This class-III receptor is a key regulator of hematopoiesis that activates signaling molecules associated with cellular processes such as proliferation, apoptosis, and differentiation. Alterations of FLT3 have been reported at a frequency of 25%-35% in adult acute myeloid leukemia (AML), the most common being an internal tandem duplication (ITD) and a missense change at amino acid position 835 (D835) in the kinase domain (International Journal of Hematology (2013) 97(6): 683-694). Identification of these mutations allows patients to be initiated with appropriate chemotherapy (such as midostaurin, sorafenib, etc.)

Turnaround Time

5 days

CPT Code(s)

81245, 81246

Cost

$500

Clinical Information

FLT3-ITD: This alteration is reported in ~23% of newly diagnosed, de novo AML cases. The insertion/duplication occurs in the juxtamembrane domain of FLT3 and nearly always includes the arginine at amino acid 595. While duplication length can vary from 3 base pairs to greater than 400 base pairs, the result is constitutive FLT3 activation. In cytogenetically normal AML, presence of FLT3-ITD confers a poor prognosis due to high relapse and adverse overall survival (Leukemia and Lymphoma (2014) 55(2): 243-255).

FLT3-D835: The aspartate located at amino acid 835 in FLT3 resides within the activation loop of its kinase domain. Missense mutations at this position are reported at ~7% frequency which is lower than ITDs, and are more commonly found in favorable risk cytogenetic patients. The prognostic impact from D835 mutations is not yet clear; however, they are therapeutically relevant because these mutations are known to confer resistance to some FLT3 inhibitors (Leukemia (2015) 29(12): 2390-2).

Indications

Identification of one or both of these mutations may have prognostic or therapeutic implications.

Specimen Requirements

Peripheral blood or bone marrow will be accepted for this test. Specimens should be collected in an EDTA, lavendar top tube.

Transport Instructions

Specimen should be kept at room temperature; do not freeze or refrigerate. Specimen should be sent by courier or overnight mail to arrive at the laboratory within 24 hours.

Have Questions Need Support?

Call our laboratory at 1-800-473-9411 or contact one of our Laboratory Genetic Counselors for assistance.
Robin Fletcher, MS, CGC
Kellie Walden, MS, CGC

Oncology Testing, Targeted Variants
Lucy's Story

Lucy's Story

When our daughter Lucy had a metabolic crisis at 7 days old, we were shocked and devastated to find out that she was born with a rare genetic disorder (MSUD). Her newborn screening results did not make it back in time to prevent the crisis, and no one at our local hospital was familiar with the disease. They did not know how to treat her. Calls were made to Greenwood Genetic Center to confirm her diagnosis...

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