• Test Code:
  • Department:
  • Test Synonyms:
    Waldenstroms Macroglobulinemia/lymphoblastic lymphomaWM/LPLMGUS
  • CPT Code(s):

The L265P activating mutation in the MYD88 gene is a common recurrent mutation in several B-cell lymphoproliferative disorders. This mutation is present in nearly all (67-100%) patients with Waldenstroms Macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) and approximately 50% of IgM MGUS patients. This mutation is also quite common in diffuse large B-cell lymphoma, especially DLBCL’s at immune privileged sites such as the skin, testis, and CNS (including ocular). It can also be detected in rare cases of low-grade B-cell lymphoma/leukemia such as marginal zone lymphoma (4%), and chronic lymphocytic leukemia/small lymphocytic lymphoma (2%). The MYD88 gene encodes a cytoplasmic adaptor protein that plays a central role in innate and adaptive immunity and functions as a key linker protein in the Toll Like Receptor (TLRs) and IL-1 receptor signaling pathway. The L265P mutation favors cell survival through IRAK1/IRAK4 and NF-kB signaling. Novel agents such as the BTK inhibitor ibrutinib are a proven effective therapy for WM and are showing promise for the treatment of DLBCL.

Reasons for Referral:
The assay is designed to allowing an accurate diagnosis of Waldenstroms Macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) and exclusion of other lymphoproliferative disorders with overlapping features, providing prognosis and predicting responses to targeted therapy.


DNA is extracted from blood, bone marrow, lymph node, CSF, or vitreous fluid.  Mutation Analysis is done by allele-specific qPCR with unique primers for the wild type and mutant allele.  Mutation-specific qPCR primers and probes are used to amplify the point mutation at position 38182641 in chromosome 3p22.2 that results in an amino-acid change from leucine to proline (L265P) in the MYD88 gene.  Sample quality is checked by qPCR amplification of the wild type MYD88 gene.  The low level sensitivity limit of this assay is about 1% mutant allele, such that a mutant allele population below this detection limit will not be reliably detected.

Specimen Requirements:

Please send one of the following:

  • Blood: 5mL EDTA (lavender top tube) or ACD (yellow top)
  • Bone Marrow Aspirate: 2-5mL EDTA (lavender top tube) or ACD (yellow top)
  • Paraffin block
  • 10 unstained sections of a bone marrow biopsy or a lymph node (4-5 microns)
  • CSF: 0.5-2.0 ml in a sealed small-volume microtube without RPMI or other additives – (ship cold, not frozen)
  • Vitreous fluid:
    • RPMI must be added to raw vitreous fluid to stabilize it for shipment.
    • Add 2-3 ml of RPMI media to each 0.5mL (or smaller) vitreous sample.
    • Ship the RPMI-diluted sampel cold (but not frozen) to KDL lab, to arrive within 24 hours of collection.
    • Include the vitreous fluid cytology report KDL can provide sterile single-use aliquots of RPMI media (contact us).
    • Vitreous fluid samples arriving in KDL without RPMI will be discarded as inadequate.
  • DNA: 200ng at a minimum of 50-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS).
Pathology report MUST accompany sample for interpretation of results

Test Performed (Days):


Turn Around Time:

7-10 days

Shipment Sensitivity Requirements:

  • Package and ship specimen at room temperature (blood or bone marrow); on cold-pack for vitreous or CSF.
  • Contact Client Services at (855) 535-1522 for shipping kits and instructions. 
  • Ship the specimen within 24 hours of collection overnight express, using the FedEx priority overnight label provided. 


  1. Varettoni et al.Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenstrom's macroglobulinemia and related lymphoid neoplasms.Blood. 2013. 121(13):2522-2528.
  2. Landgren et al. MYD88 and beyond: novel opportunities for diagnosis, prognosis and treatment in Waldenström's Macroglobulinemia.Leukemia. 2014. 28(9):1799-803.

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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