• Test Code:
    4460
  • Department:
  • Test Synonyms:
    FMS-like tyrosine kinase 3 internal tandem duplicationFLT3 D835FLT3 ITD
  • CPT Code(s):
    8124581246
Background:

FLT 3 is a receptor tyrosine kinase with important roles in hematopoietic stem cell proliferation and survival.  It is mutated in approximately one-third of cases of acute myeloid leukemia, and in a subset of patients with acute lymphoblastic leukemia.  Two major types of mutation bearing clinical significance have been described: internal tandem duplication (ITD) of 3 – 400 bp (always in-frame) in the juxtamembrane region, and a point mutation involving aspartate 835 of the kinase domain (KD).  Since ITD mutations interfere with the negative regulatory function of the juxtamembrane region and the KD point mutations most commonly involve the activation loop, both types of mutation are responsible for constitutive activation of the receptor’s kinase activity.  Current literature suggests a poorer prognosis associated with these mutations.  However, knowledge of the mutation type may impact post-induction management strategy as well as identify patients who may potentially benefit from small molecule inhibitors of FLT3 that are currently in clinical trials.

Clinical Utility:
This test is indicated at initial diagnosis of acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndromes.  It may also be indicated for re-occurrence leukemia after induction therapy on patients not initially screened for FLT3 mutations.  It is intended to aid clinical risk stratification for management planning.

Methodology:

The ITD and D835 containing regions of the FLT3 gene are amplified. The size of the ITD PCR product is determined by capillary electrophoresis. ITD mutation is expressed as percent mutant allele burden. The D835 PCR product is digested with EcoRV and the presence of the mutation is determined by capillary electrophoresis. 

Specimen Requirements:

  • 5-10 mL of blood or bone marrow — yellow (ACD) or purple (EDTA) tube.
  • DNA: 200ng at a minimum of 25ng/µL
  • If sample cannot arrive at laboratory within 24 hours of draw, refrigerate until sample can be transported, then transport at room temperature.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information. 

Test Performed (Days):

Weekly

Turn Around Time:

7-10 days

Shipment Sensitivity Requirements:

Keep specimen cold during transit, but do not ship on dry ice. Contact Client Services for shipping kit and instructions at (855) 535-1522.  Please use the cold pack provided in the KDL shipping kit.  Ship the specimen overnight express, using the FedEx priority overnight label provided. 

 

References:

  1. Acute Myeloid Leukemia, Clinical Practice Guidelines in Oncology, (v.2.2007) National Comprehensive Cancer Network.
  2. Mrozek K, et al. Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification.  Blood 2007; 109:431-448.
  3. Gilliland DG, and Griffin JD. The roles of FLT3 in hematopoiesis and leukemia. Blood 2002; 100:1532-1542.
  4.  Kiyoi H, et al. Clinical significance of FLT3 in leukemia. International Journal of Hematology 2005; 82:85-92.
  5. Nakao M, et al. Internal tandem duplication of the FLT3 gene found in acute myeloid leukemia. Leukemia 1996; 10:1911-1918.
  6. Wang L, et al. Analysis of FLT3 internal tandem duplication and D835 mutations in Chinese acute leukemia patients. Leukemia Research 2005; 29:1393-1398.
  7. Yanada M, et al. Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: a meta-analysis. Leukemia 2005; 19:1345-1349.

Additional Info:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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