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Waldenstrom's Macroglobulinemia [C88.0-]

OMIM numbers: 153600, 602170 (MYD88)162643 (CXCR4)

Dipl.-Ing. (FH) Tanja Hinrichsen

Scientific Background

Waldenstrom's macroglobulinemia (WM) belongs to the lymphoplasmacytic lymphomas (LPL) and is defined as LPL involving the bone marrow and IgM monoclonal gammopathy of any concentration. Approx. 20% of all patients with WM have a familial predisposition. Clinical manifestations include cytopenia due to infiltration of the bone marrow by the lymphoplasmocytic cells, cryoglobulinemia, cold agglutinin disease, demyelinating neuropathy and symptomatic hyperviscosity.

There are no specific chromosomal abnormalities in LPL. Approximately half of all cases with bone marrow infiltration exhibit a 6q deletion. A trisomy 4 is found in approx. 20% of all WM cases. Trisomy 3 and trisomy 18 are rare.

So far, no underlying mutation has been identified in WM. However, approximately 90% of all patients suffering from WM exhibit a somatic mutation in the MYD88 gene. The consequence is a substitution of the amino acid leucine by proline in the position 265 in MYD88 (MYD88 L265P). MYD88 is an adaptor molecule in the toll-like receptor and the interleukin-1 receptor signaling pathway and therefore plays a role in the NF-κB signaling pathway. The MYD88 L265P mutation causes a NF-κB signal transduction and therefore leads to proliferation of WM cells.

Although, in rare cases, the MYD88 L265P mutation is also observed in patients with marginal zone lymphoma and patients with IgM MGUS, the mutation can be helpful to distinguish these entities with overlapping morphological, immunophenotypical, cytogenetic and clinical properties from each other.

Approximately 30% of patients with WM show mutations in the CXCR4 gene. CXCR4 is a chemokine receptor that promotes survival of WM cells.

Basic Diagnostics Waldenstrom's Macroglobulinemia

  • Differential blood count
  • Cytochemistry
  • Immunophenotyping