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Waldenstrom macroglobulinemia

Tuesday 6 January 2004

Waldenstrom disease; Waldenstrom’s macroglobulinemia

Digital case

- JRC:7796 : Waldenstrom’s macroglobulinemia.

Definition: Waldenstrom macroglobulinemia (WM) is a clinicopathologic syndrome in which a B-cell neoplasm involving the bone marrow, usually lymphoplasmacytic lymphoma (LPL), is associated with immunoglobulin M paraprotein in the serum.

See also: lymphoplasmacytic lymphoma (LPL)


- lymphoplasmacytic lymphoma
- lymphoplasmacytoid lymphoma
- small lymphocytic lymphoma/chronic lymphocytic leukemia
- mantle cell lymphoma
- follicular lymphoma


- transformation of Waldenstrom macroglobulinemia


Waldenstrom’s macroglobulinemia is characterized by an uncontrolled clonal proliferation of terminally differentiated B lymphocytes.

The underlying etiology is not yet known but a number of risk factors have been identified. There has been an association demonstrated with the locus 6p21.3 on chromosome 6.

There is a 2- to 3-fold risk increase of developing WM in people with a personal history of autoimmune diseases with autoantibodies and particularly elevated risks associated with hepatitis, human immunodeficiency virus, and rickettsiosis.

There are genetic factors, with first-degree relatives shown to have a highly increased risk of also contracting Waldenstrom’s.

The following molecular pathways have been implicated:

- CD154/CD40
- Akt
- ubiquitination, p53 activation, cytochrome c release
- WNT/beta-catenin
- mTOR
- Bcl-2


- increased expression of miRNAs

  • miRNA-363
  • miRNA-206
  • miRNA-494
  • miRNA-155
  • miRNA-184
  • miRNA-542
  • miRNA–3p

- decreased expression

  • miRNA-9

MicroRNA-155 regulates the proliferation and growth of WM cells in vitro and in vivo, by inhibiting MAPK/ERK, PI3/AKT, and NF-kappaB pathways.

Open References

- Development of diffuse large B-cell lymphoma in a patient with Waldenström’s macroglobulinemia/lymphoplasmacytic lymphoma: clonal identity between two B-cell neoplasms. Shiseki M, Masuda A, Watanabe N, Fujii M, Kimura T, Yoshinaga K, Mori N, Teramura M, Motoji T. Hematol Rep. 2011 Aug 31;3(2):e10. PMID: 22184531 (Free)

- Typical Waldenstrom macroglobulinemia is derived from a B-cell arrested after cessation of somatic mutation but prior to isotype switch events. Sahota SS, Forconi F, Ottensmeier CH, Provan D, Oscier DG, Hamblin TJ, Stevenson FK. Blood. 2002 Aug 15;100(4):1505-7. PMID: 12149241[Free]


- Lin P, Bueso-Ramos C, Wilson CS, Mansoor A, Medeiros LJ. Waldenstrom macroglobulinemia involving extramedullary sites: morphologic and immunophenotypic findings in 44 patients. Am J Surg Pathol. 2003 Aug;27(8):1104-13. PMID: 12883242